Bio


Dr David M. Maahs is Professor of Pediatrics and Division Chief of Pediatric Endocrinology at Stanford University and the Lucile Packard Children’s Hospital. He earned his MD followed by Pediatric Residency at the University of New Mexico. After 3 years on New Mexico’s faculty, Dr. Maahs completed a Pediatric Endocrinology fellowship and a concurrent PhD in Epidemiology at the University of Colorado. He remained on Colorado’s faculty for 10 years, advancing to Professor of Pediatrics before moving to Stanford. Prior to his medical career, Dr. Maahs received a BA and MA in English from the University of Kansas and was inspired to pursue a medical career after serving in the Peace Corps with assignments in Tunisia and the Central African Republic.

Dr. Maahs’ leadership experiences include being a past co-Chair (2013-16) for Protocols and Publications with the Type 1 Diabetes Exchange for which he continues as a Steering Committee member and Director of International Collaborations. This complements his role as Secretary-General for the International Society of Pediatric and Adolescent Diabetes (ISPAD, 2016-20) and Editor-in-Chief for the 2018 ISPAD Clinical Practice Consensus Guidelines. He currently serves on the Professional Practice Committee for the American Diabetes Association (ADA, 2016-18), which writes the annual ADA Standards of Care. Previously, he served on the ADA Scientific Sessions committee representing the Council on Youth. He has also served on national committees for the American Heart Association, the Pediatric Endocrine Society, and multiple journal editorial boards and review committees.

His scholarly interest is improving care and preventing complications in people with type 1 diabetes (T1D). Along with Dr Peter Chase, he is author of the 12th and 13th editions of Understanding Diabetes, or ‘Pink Panther,’ which are the most widely used educational books for children newly diagnosed with T1D, distributed internationally by the Juvenile Diabetes Research Fund (JDRF). More specifically, he has conducted epidemiologic studies that help generate hypotheses for clinical studies, including trials to develop artificial pancreas systems to improve glucose control, lower disease burden, and prevent diabetic complications. He is author or co-author of over 250 research publications. His multi-disciplinary research has been funded by the JDRF, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), the Helmsley Charitable Trust, and the National Science Foundation (NSF).

Dr Maahs is Associate Director for the recently formed and NIDDK P30 funded Stanford University Diabetes Research Center (https://sdrc.stanford.edu). His collaborations extend to his role as Principal Investigator (PI) or steering committee member for NIH funded multi-center clinical trials including the FLEX, PERL, and ACTION studies as well as multiple Artificial Pancreas clinical trials. Education, mentorship, and training leadership includes being Program Director with Dr. Georgeanna Klingensmith on the Barbara Davis Center T32 and K12 training grants in Pediatric Endocrinology while at the University of Colorado.

While in the Peace Corps, David met his wife, Christine Walravens, who is also a Pediatrician at Stanford. They enjoy outdoor activities and traveling with their children, Nicholas (20) and Natalia (15).

Clinical Focus


  • Pediatric Endocrinology

Academic Appointments


Boards, Advisory Committees, Professional Organizations


  • Associate Editor, Diabetes Technology and Therapeutics (2011 - 2013)
  • Co-Chair for Protocols and Publications, Type 1 Diabetes Exchange (2013 - 2016)
  • Editorial Board, Diabetes Technology and Therapeutics (2013 - Present)
  • Steering Committee, Type 1 Diabetes Exchange (2013 - Present)
  • Editor in Chief, ISPAD Guidelines 2018 (2016 - 2018)
  • Secretary-General, International Society of Pediatric and Adolescent Diabetes (2016 - Present)
  • Associate Editor, Diabetic Medicine (2017 - Present)
  • Editorial Board, Journal of Pediatrics (2017 - Present)
  • Professional Practice Committee, American Diabetes Association (2017 - Present)

Professional Education


  • PhD, University of Colorado, Analytic Health Sciences/Epidemiology (2010)
  • MA, University of Kansas, English (1990)
  • BA, University of Kansas, English (1988)
  • Board Certification: Pediatric Endocrinology, American Board of Pediatrics (2007)
  • Fellowship:University of Colorado Childrens Hospital (2006) CO
  • Board Certification: Pediatrics, American Board of Pediatrics (2000)
  • Residency:University of New Mexico Pediatric Residency (2000) NM
  • Medical Education:University of New Mexico School of Medicine (1997) United States of America

Community and International Work


  • International Society of Pediatric and Adolescent Diabetes (ISPAD)

    Topic

    Secretary-General 2016-2020

    Populations Served

    Children, adolescents, and young adults with diabetes internationally

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Clinical Trials


  • Remote Monitoring of Diabetes in Young Children With Type 1 Diabetes Recruiting

    The primary objective of this project is to examine the impact of a continuous glucose monitoring (CGM) intervention on health and psychological outcomes in young children with type 1 diabetes (T1D).

    View full details

All Publications


  • Efficacy of the Flexible Lifestyles Empowering Change intervention on metabolic and psychosocial outcomes in adolescents with type 1 diabetes (FLEX): a randomised controlled trial LANCET CHILD & ADOLESCENT HEALTH Mayer-Davis, E. J., Maahs, D. M., Seid, M., Crandell, J., Bishop, F. K., Driscoll, K. A., Hunter, C. M., Kichler, J. C., Standiford, D., Thomas, J. M., FLEX Study Grp 2018; 2 (9): 635–46

    Abstract

    Adolescents with type 1 diabetes commonly have poor glycaemic control. We aimed to test the efficacy of a newly developed adaptive behavioral intervention (Flexible Lifestyles Empowering Change; FLEX) on metabolic and psychosocial outcomes in adolescents with type 1 diabetes.Young people (13-16 years, type 1 diabetes duration >1 year, HbA1c of 64-119 mmol/mol [8·0-13·0%], and without other serious medical conditions or pregnancy) from two clinical sites (Colorado and Ohio, USA) were eligible for enrolment. One caregiver was required to participate actively in the study. Adolescent participants were randomly assigned to the FLEX intervention, which used motivational interviewing and problem-solving skills training to enhance patients' self-management, or usual care control. Intervention fidelity was assessed by a behavioral psychologist with specific expertise in motivational interviewing and who was not otherwise involved in the study via audiotaped sessions. The primary outcome was measurement of glycated haemoglobin A1c (HbA1c) at 18 months. Secondary outcomes included motivation and intention, problem solving skills, self-management behaviors, symptoms of depression, health related quality of life, fear of hypoglycemia, diabetes family conflict, risk factors for T1D complications (BMI, blood pressure, and plasma lipids), and hypoglycemia derived from continuous glucose monitoring (percent time below 3·0 and 3·9 mmol/l [54 and 70 mg/dl]). Intention-to-treat analyses used mixed effects models, with fixed effects including site, timepoint, intervention group, intervention by timepoint, and baseline level of primary (HbA1c) or secondary outcomes (α=0·05). FLEX is registered on clinicaltrials.gov, number NCT01286350.Young people recruited from May 1, 2014 to April 4, 2016 were randomly assigned to FLEX (n=130) or usual care control (n=128). Mean diabetes duration was 6·4 (SD 3·8) years, and 71% (181 out of 256) of patients used insulin pump therapy. Retention was 93%, with 241 out of 258 completing the 18-month assessment. The intervention fidelity score was 4·40 of 5·00 for motivational interviewing and 97% for session content. At 18 months, HbA1c was not significantly different between intervention (83 [13] mmol/mol at baseline; 84 [19] mmol/mol at follow-up); and control (80 [14] mmol/mol at baseline; 82 [17] mmol/mol at follow-up); change in intervention versus control was -0·7 mmol/mol (95% CI -4·7 to 3·4, p=0·75). The intervention was associated with improved scores for motivation (p=0·011), problem solving (p=0·024), diabetes self-management profile (p=0·013), youth report of overall quality of life (p=0·0089), selected domains related to fear of hypoglycaemia (p=0·036 for youth's helplessness or worry; p=0·0051 for parent's efforts to maintain high blood glucose), parent report of diabetes family conflict (p=0·0001), total cholesterol (p=0·038), and diastolic blood pressure (p=0·015). A total of 54 serious adverse events were identified; 34 of these were diabetes-related, including low blood glucose requiring assistance (n=3) and high blood glucose with diabetic ketoacidosis and emergency response (n=25).The FLEX intervention did not significantly change HbA1c among these adolescents with elevated HbA1c, but did positively affect several psychosocial outcomes over 18 months. Further analyses will provide information regarding drivers of positive response to the intervention and will point to future directions for improvement in the approach.National Institutes of Health and National Institute of Diabetes Digestive Diseases and Kidney and the Helmsley Charitable Trust.

    View details for DOI 10.1016/S2352-4642(18)30208-6

    View details for Web of Science ID 000441503600015

    View details for PubMedID 30119757

  • Age at type 1 diabetes onset: a new risk factor and call for focused treatment LANCET Basina, M., Maahs, D. M. 2018; 392 (10146): 453–54
  • Sustained Continuous Glucose Monitor Use in Low-Income Youth with Type 1 Diabetes Following Insurance Coverage Supports Expansion of Continuous Glucose Monitor Coverage for All. Diabetes technology & therapeutics Prahalad, P., Addala, A., Buckingham, B., Wilson, D. M., Maahs, D. M. 2018

    View details for DOI 10.1089/dia.2018.0204

    View details for PubMedID 30020810

  • Can Real World Evidence on Body Mass Index Trajectories Inform Clinical Practice? The Journal of pediatrics Addala, A., Maahs, D. M. 2018

    View details for DOI 10.1016/j.jpeds.2018.06.062

    View details for PubMedID 30025670

  • Type 2 diabetes mellitus (T2DM) in youth. Pediatric diabetes Zeitler, P., Arslanian, S., Fu, J., Pinhas-Hamiel, O., Reinehr, T., Tandon, N., Urakami, T., Wong, J., Maahs, D. M. 2018

    Abstract

    The 2018 ISPAD Guidelines have been updated based on published data and evolving expert opinion since the 2014 chapter was published, including treatment target (HbA1c=7%) and intensification of management recommendations. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/pedi.12719

    View details for PubMedID 29999228

  • Diabetes Technology Use Among Pregnant and Nonpregnant Women with T1D in the T1D Exchange. Diabetes technology & therapeutics Polsky, S., Wu, M., Bode, B. W., DuBose, S. N., Goland, R. S., Maahs, D. M., Foster, N. C., Peters, A. L., Levy, C. J., Shah, V. N., Beck, R. W. 2018

    Abstract

    BACKGROUND: Gestational tight glycemic control is critical for women with type 1 diabetes (T1D). Limited data exist on the adoption and retention of diabetes technologies among women in different parity strata.METHODS: We compared T1D management between T1D Exchange clinic registry participants (mean age 28±9 years, 84% white non-Hispanic, and median T1D duration 13 years) who were pregnant at enrollment or year 1 follow-up ("recently pregnant" between 2010 and 2013, n=214), ever (but not recently) pregnant (n=1540), and never pregnant (n=2586). We examined self-reported maternal and fetal outcomes in 130 women who delivered a baby within the last year.RESULTS: Recently pregnant women had the lowest hemoglobin A1c (6.5% pregnant vs. 7.8% ever pregnant vs. 8.0% never pregnant, P<0.001). Recently pregnant women reported the highest use of continuous subcutaneous insulin infusion (74% vs. 60% vs. 58%, adjusted P<0.001) and continuous glucose monitor (CGM) (36% vs.17% vs. 12%, adjusted P<0.001) therapies compared with ever or never pregnant women, respectively, after adjusting for age, diabetes duration, and socioeconomic status. Among women 18-25 years old, CGM use was highest among recently pregnant women (adjusted P=0.0022). Never pregnant women 26-45 years old had a higher use of CGM compared with younger counterparts (adjusted P<0.001). Adverse maternal and fetal outcomes were common.CONCLUSIONS: Despite high uptake levels of advanced diabetes technologies among pregnant women, rates of adverse maternal and fetal outcomes remain high. More studies are needed to determine how these technologies could be best used in pregnancy and postpartum to improve health outcomes among women with T1D.

    View details for DOI 10.1089/dia.2018.0033

    View details for PubMedID 29990438

  • Eating patterns and food intake of persons with type 1 diabetes within the T1D exchange DIABETES RESEARCH AND CLINICAL PRACTICE Powers, M. A., Gal, R. L., Connor, C. G., Mangan, M., Maahs, D. M., Clements, M. A., Mayer-Davis, E. J. 2018; 141: 217–28

    Abstract

    To identify dietary intake and eating patterns of people with type 1 diabetes from childhood to later adulthood in relation to HbA1c.Trained interviewers conducted 24-hour recalls via phone utilizing a multiple pass approach and administered two nutrition questionnaires; 463 participants (or parents of participants) within the T1D Exchange clinic registry were included. Participants were 5 to 81 years with 80-101 participants in five age groups; 56% were female, and 92% were white, with a median diabetes duration of 11.1 years and a median HbA1c of 7.4% [57 mmol/mol]).Those with type 1 diabetes consumed less calories from carbohydrates and more from fats and protein than those in the general population, based on the National Health and Nutrition Examination Survey data. Carbohydrate intake was not correlated with HbA1c levels. Increased fiber intake, more eating occasions, higher Healthy Eating Index scores, and higher nutrition knowledge scores were each associated with lower HbA1c levels.Food intake, eating patterns and nutrition knowledge are associated with glycemic control across a registry-based cohort of adults and children with type 1 diabetes. Additionally, these data can inform the design of future studies to advance our understanding of nutritional influences on type 1 diabetes self-care and control.

    View details for DOI 10.1016/j.diabres.2018.05.011

    View details for Web of Science ID 000436462900026

    View details for PubMedID 29772288

  • Advances in Care for Insulin-Requiring Patients Without Closed Loop. Diabetes technology & therapeutics Lal, R. A., Buckingham, B., Maahs, D. M. 2018; 20 (S2): S285–S291

    View details for DOI 10.1089/dia.2018.0084

    View details for PubMedID 29916743

  • Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes DIABETES CARE Charalampopoulos, D., Hermann, J. M., Svensson, J., Skrivarhaug, T., Maahs, D. M., Akesson, K., Warner, J. T., Holl, R. W., Birkebaek, N. H., Drivvoll, A. K., Miller, K. M., Svensson, A., Stephenson, T., Hofer, S. E., Fredheim, S., Kummernes, S. J., Foster, N., Hanberger, L., Amin, R., Rami-Merhar, B., Johansen, A., Dahl-Jorgensen, K., Clements, M., Hanas, R. 2018; 41 (6): 1180–87

    Abstract

    International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA1c levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA1c across and within eight high-income countries to best inform international benchmarking and policy recommendations.Data were collected between 2013 and 2014 from 64,666 children with T1D who were <18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed- and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA1c levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and children's glycemic control.Sweden had the lowest mean HbA1c (59 mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC ≤4%). Germany and Austria had the next lowest mean HbA1c (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC ∼15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value <0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA1c levels (5.6 mmol/mol [0.5%] per 5 mmol/mol [0.5%] increase in center SD of HbA1c values of all children attending a specific center).At similar average levels of HbA1c, countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.

    View details for DOI 10.2337/dc17-2271

    View details for Web of Science ID 000432673000023

    View details for PubMedID 29650804

    View details for PubMedCentralID PMC5961394

  • Guidelines to Practice: Identifying Barriers to Cardiovascular Health Management in Pediatric Type 1 Diabetes. The Journal of pediatrics Maahs, D. M. 2018; 197: 14–15

    View details for DOI 10.1016/j.jpeds.2018.01.047

    View details for PubMedID 29551320

  • Predictive hyperglycemia and hypoglycemia minimization: In-home double-blind randomized controlled evaluation in children and young adolescents PEDIATRIC DIABETES Forlenza, G. P., Raghinaru, D., Cameron, F., Bequette, B., Chase, H., Wadwa, R., Maahs, D. M., Jost, E., Ly, T. T., Wilson, D. M., Norlander, L., Ekhlaspour, L., Min, H., Clinton, P., Njeru, N., Lum, J. W., Kollman, C., Beck, R. W., Buckingham, B. A., In-Home Closed-Loop IHCL Study Grp 2018; 19 (3): 420–28

    Abstract

    The primary objective of this trial was to evaluate the feasibility, safety, and efficacy of a predictive hyperglycemia and hypoglycemia minimization (PHHM) system vs predictive low glucose suspension (PLGS) alone in optimizing overnight glucose control in children 6 to 14 years old.Twenty-eight participants 6 to 14 years old with T1D duration ≥1 year with daily insulin therapy ≥12 months and on insulin pump therapy for ≥6 months were randomized per night into PHHM mode or PLGS-only mode for 42 nights. The primary outcome was percentage of time in sensor-measured range 70 to 180 mg/dL in the overnight period.The addition of automated insulin delivery with PHHM increased time in target range (70-180 mg/dL) from 66 ± 11% during PLGS nights to 76 ± 9% during PHHM nights (P<.001), without increasing hypoglycemia as measured by time below various thresholds. Average morning blood glucose improved from 176 ± 28 mg/dL following PLGS nights to 154 ± 19 mg/dL following PHHM nights (P<.001).The PHHM system was effective in optimizing overnight glycemic control, significantly increasing time in range, lowering mean glucose, and decreasing glycemic variability compared to PLGS alone in children 6 to 14 years old.

    View details for DOI 10.1111/pedi.12603

    View details for Web of Science ID 000430921600013

    View details for PubMedID 29159870

  • Fully Closed-Loop Multiple Model Probabilistic Predictive Controller Artificial Pancreas Performance in Adolescents and Adults in a Supervised Hotel Setting DIABETES TECHNOLOGY & THERAPEUTICS Forlenza, G. P., Cameron, F. M., Ly, T. T., Lam, D., Howsmon, D. P., Baysal, N., Kulina, G., Messer, L., Clinton, P., Levister, C., Patek, S. D., Levy, C. J., Wadwa, R., Maahs, D. M., Bequette, B., Buckingham, B. A. 2018; 20 (5): 335–43

    Abstract

    Initial Food and Drug Administration-approved artificial pancreas (AP) systems will be hybrid closed-loop systems that require prandial meal announcements and will not eliminate the burden of premeal insulin dosing. Multiple model probabilistic predictive control (MMPPC) is a fully closed-loop system that uses probabilistic estimation of meals to allow for automated meal detection. In this study, we describe the safety and performance of the MMPPC system with announced and unannounced meals in a supervised hotel setting.The Android phone-based AP system with remote monitoring was tested for 72 h in six adults and four adolescents across three clinical sites with daily exercise and meal challenges involving both three announced (manual bolus by patient) and six unannounced (no bolus by patient) meals. Safety criteria were predefined. Controller aggressiveness was adapted daily based on prior hypoglycemic events.Mean 24-h continuous glucose monitor (CGM) was 157.4 ± 14.4 mg/dL, with 63.6 ± 9.2% of readings between 70 and 180 mg/dL, 2.9 ± 2.3% of readings <70 mg/dL, and 9.0 ± 3.9% of readings >250 mg/dL. Moderate hyperglycemia was relatively common with 24.6 ± 6.2% of readings between 180 and 250 mg/dL, primarily within 3 h after a meal. Overnight mean CGM was 139.6 ± 27.6 mg/dL, with 77.9 ± 16.4% between 70 and 180 mg/dL, 3.0 ± 4.5% <70 mg/dL, 17.1 ± 14.9% between 180 and 250 mg/dL, and 2.0 ± 4.5%> 250 mg/dL. Postprandial hyperglycemia was more common for unannounced meals compared with announced meals (4-h postmeal CGM 197.8 ± 44.1 vs. 140.6 ± 35.0 mg/dL; P < 0.001). No participants met safety stopping criteria.MMPPC was safe in a supervised setting despite meal and exercise challenges. Further studies are needed in a less supervised environment.

    View details for DOI 10.1089/dia.2017.0424

    View details for Web of Science ID 000430263800001

    View details for PubMedID 29658779

    View details for PubMedCentralID PMC5963546

  • Meta-genome-wide association studies identify a locus on chromosome 1 and multiple variants in the MHC region for serum C-peptide in type 1 diabetes DIABETOLOGIA Roshandel, D., Gubitosi-Klug, R., Bull, S. B., Canty, A. J., Pezzolesi, M. G., King, G. L., Keenan, H. A., Snell-Bergeon, J. K., Maahs, D. M., Klein, R., Klein, B. K., Orchard, T. J., Costacou, T., Weedon, M. N., Oram, R. A., Paterson, A. D., DCCT EDIC Res Grp 2018; 61 (5): 1098–1111

    Abstract

    The aim of this study was to identify genetic variants associated with beta cell function in type 1 diabetes, as measured by serum C-peptide levels, through meta-genome-wide association studies (meta-GWAS).We performed a meta-GWAS to combine the results from five studies in type 1 diabetes with cross-sectionally measured stimulated, fasting or random C-peptide levels, including 3479 European participants. The p values across studies were combined, taking into account sample size and direction of effect. We also performed separate meta-GWAS for stimulated (n = 1303), fasting (n = 2019) and random (n = 1497) C-peptide levels.In the meta-GWAS for stimulated/fasting/random C-peptide levels, a SNP on chromosome 1, rs559047 (Chr1:238753916, T>A, minor allele frequency [MAF] 0.24-0.26), was associated with C-peptide (p = 4.13 × 10-8), meeting the genome-wide significance threshold (p < 5 × 10-8). In the same meta-GWAS, a locus in the MHC region (rs9260151) was close to the genome-wide significance threshold (Chr6:29911030, C>T, MAF 0.07-0.10, p = 8.43 × 10-8). In the stimulated C-peptide meta-GWAS, rs61211515 (Chr6:30100975, T/-, MAF 0.17-0.19) in the MHC region was associated with stimulated C-peptide (β [SE] = - 0.39 [0.07], p = 9.72 × 10-8). rs61211515 was also associated with the rate of stimulated C-peptide decline over time in a subset of individuals (n = 258) with annual repeated measures for up to 6 years (p = 0.02). In the meta-GWAS of random C-peptide, another MHC region, SNP rs3135002 (Chr6:32668439, C>A, MAF 0.02-0.06), was associated with C-peptide (p = 3.49 × 10-8). Conditional analyses suggested that the three identified variants in the MHC region were independent of each other. rs9260151 and rs3135002 have been associated with type 1 diabetes, whereas rs559047 and rs61211515 have not been associated with a risk of developing type 1 diabetes.We identified a locus on chromosome 1 and multiple variants in the MHC region, at least some of which were distinct from type 1 diabetes risk loci, that were associated with C-peptide, suggesting partly non-overlapping mechanisms for the development and progression of type 1 diabetes. These associations need to be validated in independent populations. Further investigations could provide insights into mechanisms of beta cell loss and opportunities to preserve beta cell function.

    View details for DOI 10.1007/s00125-018-4555-9

    View details for Web of Science ID 000428796200013

    View details for PubMedID 29404672

    View details for PubMedCentralID PMC5876265

  • HUMAN FACTORS DURING TRIAL OF A HYBRID CLOSED LOOP SYSTEM FOR TYPE 1 DIABETES MANAGEMENT Adams, R. N., Tanenbaum, M. L., Hanes, S. J., Ambrosino, J. M., Ly, T. T., Maahs, D. M., Naranjo, D., Walders-Abramson, N., Weinzimer, S. A., Buckingham, B. A., Hood, K. K. OXFORD UNIV PRESS INC. 2018: S718
  • Sex-specific differences in insulin resistance in type 1 diabetes: The CACTI cohort JOURNAL OF DIABETES AND ITS COMPLICATIONS Millstein, R. J., Pyle, L. L., Bergman, B. C., Eckel, R. H., Maahs, D. M., Rewers, M. J., Schauer, I. E., Snell-Bergeon, J. K. 2018; 32 (4): 418–23

    Abstract

    To test the hypothesis that multitissue deficits in insulin sensitivity are greater among women than men with type 1 diabetes compared to respective controls.Three-stage hyperinsulinemic-euglycemic clamps (4, 8, 40 mU/m2/min) were performed on 41 people with type 1 diabetes and 47 adults without diabetes (mean ± SD age 46 ± 8). Infusions of [1-13C]palmitate, [1,1,2,3,3-2H2]glycerol, and [6,6-2H2]glucose isotope tracers were used to determine free fatty acid (FFA), glycerol, and glucose kinetics in 52 of these participants (25 M and 27 W).There was no difference in age or BMI by type 1 diabetes status in either sex. Free fatty acid rate of appearance (FFA Ra) was higher in both sexes with type 1 diabetes compared to those without diabetes during stages 1 and 2. The same was seen with glycerol for stages 1 and 2. During stage 3 glucose rate of disappearance (Rd) was lower in those with type 1 diabetes among both sexes. All had sex by type 1 diabetes interactions with greater deficits in insulin sensitivity in women. While there was no sex by diabetes interaction in regards to glucose rate of appearance (Ra), those with type 1 diabetes had a higher glucose Ra than those without diabetes.We found that type 1 diabetes affected adipose and skeletal muscle insulin sensitivity to a greater extent in women than in men, perhaps contributing to the greater relative increase in cardiovascular risk in women with type 1 diabetes.

    View details for DOI 10.1016/j.jdiacomp.2018.01.002

    View details for Web of Science ID 000428361500012

    View details for PubMedID 29449137

    View details for PubMedCentralID PMC5856232

  • Role of bicarbonate supplementation on urine uric acid crystals and diabetic tubulopathy in adults with type 1 diabetes. Diabetes, obesity & metabolism Bjornstad, P., Maahs, D. M., Roncal, C. A., Snell-Bergeon, J. K., Shah, V. N., Milagres, T., Ellis, S. L., Hatch, M., Chung, L. T., Rewers, M. J., Garg, S., Cherney, D. Z., Pyle, L., Nadeau, K. J., Johnson, R. J. 2018

    Abstract

    Uricosuria and crystallization are increasingly recognized risk factors for diabetic tubulopathy. This pilot clinical trial aimed to determine the acute effect of urinary alkalinization using oral sodium bicarbonate (NaHCO3 ) on UA crystals in adults with type 1 diabetes (T1D). Adults with T1D, ages 18 to 65years (n=45, 60% female, HbA1c, 7.5±1.2%, 20.2±9.3 years duration) without chronic kidney disease (eGFR ≥60mL/min/1.73m2 and albumin-to-creatinine ratio<30mg/g) received 2 doses of 1950mg oral NaHCO3 over 24hours. Fasting urine and serum were collected pre- and post-intervention. UA crystals were identified under polarized microscopy. Urine measurements included: osmolality, pH, UA, creatinine and kidney injury molecule-1 (KIM-1). NaHCO3 therapy increased mean±SD urine pH from 6.1±0.7 to 6.5±0.7 (P<.0001). Prior to therapy, 31.0% of participants had UA crystals vs 6.7% post therapy (P=.005). Change in urine pH inversely correlated with change in urine KIM-1 (r:-0.51, P=.0003). In addition, change in urine UA over 24hours correlated with change in urine KIM-1 (r:0.37, P=.01). In conclusion, oral NaHCO3 normalized urine pH and decreased UA crystals, and may hold promise as an inexpensive and safe tubulo-protective intervention in individuals with T1D.

    View details for DOI 10.1111/dom.13274

    View details for PubMedID 29498467

  • Quantifying genetic susceptibility in T1DM-implications for diagnosis after age 30 NATURE REVIEWS ENDOCRINOLOGY Meyer, E., Maahs, D. M. 2018; 14 (3): 134–35

    View details for DOI 10.1038/nrendo.2018.7

    View details for Web of Science ID 000424668800011

    View details for PubMedID 29422635

  • The Flexible Lifestyle Empowering Change (FLEX) intervention for self-management in adolescents with type 1 diabetes: Trial design and baseline characteristics CONTEMPORARY CLINICAL TRIALS Kichler, J. C., Seid, M., Crandell, J., Maahs, D. M., Bishop, F. K., Driscoll, K. A., Standiford, D., Hunter, C. M., Mayer-Davis, E. 2018; 66: 64–73

    Abstract

    The Flexible Lifestyle Empowering Change (FLEX) Intervention Study is a multi-site randomized controlled trial to test the efficacy of an adaptive behavioral intervention to promote self-management for youth with type 1 diabetes mellitus (T1D). This paper details FLEX design, demographic characteristics of the sample, and outcome variables at baseline. Participants were randomized to either an intervention or control arm after their baseline standardized measurement visit. Baseline data for the primary (glycemic levels) and secondary outcome variables (e.g., motivation and problem-solving, health-related quality of life, risk factors associated with T1D complications) as well as the potential mediator variables (e.g., self-management behavior, family conflict and responsibility) suggest that the study sample was representative of the general population of adolescents with T1D and their parents. The FLEX adaptive intervention is an innovative application of a tailored treatment intervention designed to be readily adopted in real-world practice to meet each adolescent's individualized T1D self-management goals.

    View details for DOI 10.1016/j.cct.2017.12.006

    View details for Web of Science ID 000428105000008

    View details for PubMedID 29277316

    View details for PubMedCentralID PMC5828911

  • Macrovascular disease and risk factors in youth with type 1 diabetes: time to be more attentive to treatment? The lancet. Diabetes & endocrinology Bjornstad, P., Donaghue, K. C., Maahs, D. M. 2018

    Abstract

    Cardiovascular disease remains the leading cause of mortality in patients with type 1 diabetes. Although cardiovascular disease complications are rare until adulthood, pathology and early markers can manifest in adolescence. Whereas advances have been made in the management of microvascular complications of type 1 diabetes, similar progress in reducing macrovascular complications has not been made. The reasons for the absence of progress remain incompletely understood, but most likely relate to the long time needed for cardiovascular disease to manifest clinically and hence for risk factor management to show a clinical benefit, thus allowing inertia to prevail for diagnosis and particularly for targeting risk factors. In this Review, we summarise paediatric data on traditional and novel risk factors of cardiovascular disease, provide an overview of data from previous and current clinical trials, discuss future directions in cardiovascular disease research for paediatric patients with type 1 diabetes, and advocate for the early identification and treatment of cardiovascular disease risk factors as recommended in multiple guidelines.

    View details for DOI 10.1016/S2213-8587(18)30035-4

    View details for PubMedID 29475800

  • The dawn of automated insulin delivery: A new clinical framework to conceptualize insulin administration PEDIATRIC DIABETES Messer, L. H., Forlenza, G. P., Wadwa, R., Weinzimer, S. A., Sherr, J. L., Hood, K. K., Buckingham, B. A., Slover, R. H., Maahs, D. M. 2018; 19 (1): 14–17

    View details for DOI 10.1111/pedi.12535

    View details for Web of Science ID 000423397600003

    View details for PubMedID 28656656

  • Overnight Hypoglycemia and Hyperglycemia Mitigation for Individuals with Type 1 Diabetes HOW RISKS CAN BE REDUCED IEEE CONTROL SYSTEMS MAGAZINE Bequette, B., Cameron, F., Buckingham, B. A., Maahs, D. M., Lum, J. 2018; 38 (1): 125–34
  • Diabetes technology: improving care, improving patient-reported outcomes and preventing complications in young people with Type 1 diabetes. Diabetic medicine : a journal of the British Diabetic Association Prahalad, P., Tanenbaum, M., Hood, K., Maahs, D. M. 2018

    Abstract

    With the evolution of diabetes technology, those living with Type 1 diabetes are given a wider arsenal of tools with which to achieve glycaemic control and improve patient-reported outcomes. Furthermore, the use of these technologies may help reduce the risk of acute complications, such as severe hypoglycaemia and diabetic ketoacidosis, as well as long-term macro- and microvascular complications. In addition, diabetes technology can have a beneficial impact on psychosocial health by reducing the burden of diabetes. Unfortunately, diabetes goals are often unmet and people with Type 1 diabetes too frequently experience acute and long-term complications of this condition, in addition to often having less than ideal psychosocial outcomes. Increasing realization of the importance of patient-reported outcomes is leading to diabetes care delivery becoming more patient-centred. Diabetes technology in the form of medical devices, digital health and big data analytics have the potential to improve clinical care and psychosocial support, resulting in lower rates of acute and chronic complications, decreased burden of diabetes care, and improved quality of life. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/dme.13588

    View details for PubMedID 29356074

  • Measured GFR in Routine Clinical Practice-The Promise of Dried Blood Spots ADVANCES IN CHRONIC KIDNEY DISEASE Bjornstad, P., Karger, A. B., Maahs, D. M. 2018; 25 (1): 76–83

    Abstract

    Accurate determination of glomerular filtration rate (GFR) is crucial for the diagnosis of kidney disease. Estimated GFR (eGFR) calculated by serum creatinine and/or cystatin C is a mainstay in clinical practice and epidemiologic research but lacks precision and accuracy until GFR <60 mL/min/1.73 m2. Furthermore, eGFR may not precisely and accurately represent changes in GFR longitudinally. The lack of precision and accuracy is of concern in populations at high risk for kidney disease, as the dissociation between changes in eGFR and GFR may lead to missed diagnoses of early kidney disease. Therefore, improved methods to quantify GFR are needed. Whereas direct measures of GFR have been too cumbersome for screening and ambulatory care, a practical method of measuring GFR by iohexol clearance using dried capillary blood spots exists. In this review, we examine the current literature and data addressing GFR measurements by dried capillary blood spots and its potential application in high-risk groups.

    View details for DOI 10.1053/j.ackd.2017.09.003

    View details for Web of Science ID 000428001300011

    View details for PubMedID 29499891

    View details for PubMedCentralID PMC5836491

  • Dynamic changes in retinal vessel diameter during acute hyperglycemia in type 1 diabetes. Journal of diabetes and its complications Bucca, B. C., Maahs, D. M., Snell-Bergeon, J. K., Hokanson, J., Rinella, S., Bishop, F., Boufard, A., Homann, J., Cheung, C. Y., Wong, T. Y. 2018; 32 (2): 234–39

    Abstract

    To investigate changes in retinal vessel diameter during acute hyperglycemia in patients with type 1 diabetes.We conducted a study on 11 subjects with type 1 diabetes. Euglycemia was maintained for 3h followed by induction of hyperglycemia and simultaneous bolus of rapid acting insulin. Two fundus photos were captured during euglycemia and five fundus photos, blood glucose and blood pressure were taken every 30min for 2.5h post-prandial. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were measured over the study visit and examined using generalized linear mixed models.In a multivariate mixed model, mean CRAE and CRVE were reduced at 90min post-prandial in both zones B and C. In repeated measures analysis, arterioles exhibited a significant association with change in vessel caliber per change in blood glucose. Inconsistent effects of blood pressure on vessel diameter were also measured.We document a change in retinal vessel diameter during acute hyperglycemia in persons with type 1 diabetes. Larger controlled studies are required to further investigate this phenomenon and to more accurately assess if hyperglycemia has direct effects on retinal vessel diameter.

    View details for DOI 10.1016/j.jdiacomp.2017.10.001

    View details for PubMedID 29174301

  • Diabetes Technology and Therapy in the Pediatric Age Group. Diabetes technology & therapeutics Maahs, D. M., Shalitin, S. 2018; 20 (S1): S114–S127

    View details for DOI 10.1089/dia.2018.2510

    View details for PubMedID 29437470

  • Optimizing Hybrid Closed-Loop Therapy in Adolescents and Emerging Adults Using the MiniMed 670G System. Diabetes care Messer, L. H., Forlenza, G. P., Sherr, J. L., Wadwa, R. P., Buckingham, B. A., Weinzimer, S. A., Maahs, D. M., Slover, R. H. 2018; 41 (4): 789–96

    Abstract

    The MiniMed 670G System is the first commercial hybrid closed-loop (HCL) system for management of type 1 diabetes. Using data from adolescent and young adult participants, we compared insulin delivery patterns and time-in-range metrics in HCL (Auto Mode) and open loop (OL). System alerts, usage profiles, and operational parameters were examined to provide suggestions for optimal clinical use of the system.Data from 31 adolescent and young adult participants (14-26 years old) at three clinical sites in the 670G pivotal trial were analyzed. Participants had a 2-week run-in period in OL, followed by a 3-month in-home study phase with HCL functionality enabled. Data were compared between baseline OL and HCL use after 1 week, 1 month, 2 months, and 3 months.Carbohydrate-to-insulin (C-to-I) ratios were more aggressive for all meals with HCL compared with baseline OL. Total daily insulin dose and basal-to-bolus ratio did not change during the trial. Time in range increased 14% with use of Auto Mode after 3 months (P< 0.001), and HbA1cdecreased 0.75%. Auto Mode exits were primarily due to sensor/insulin delivery alerts and hyperglycemia. The percentage of time in Auto Mode gradually declined from 87%, with a final use rate of 72% (-15%).In transitioning young patients to the 670G system, providers should anticipate immediate C-to-I ratio adjustments while also assessing active insulin time. Users should anticipate occasional Auto Mode exits, which can be reduced by following system instructions and reliably bolusing for meals. Unique 670G system functionality requires ongoing clinical guidance and education from providers.

    View details for DOI 10.2337/dc17-1682

    View details for PubMedID 29444895

  • Familial Holoprosencephaly with Endocrine Dysgenesis JOURNAL OF PEDIATRICS Chang, M., Wilson, D. M., Maahs, D. M. 2018; 192: 98
  • Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Greenbaum, C., Atkinson, M., Baidal, D., Battaglia, M., Bingley, P., Bosi, E., Buckner, J., Clements, M., Colman, P., DiMeglio, L., Evans-Molina, C., Gitelman, S., Goland, R., Gottlieb, P., Herold, K., Knip, M., Krischer, J., Lernmark, A., Moore, W., Moran, A., Muir, A., Palmer, J., Peakman, M., Philipson, L., Raskin, P., Redondo, M., Rodriguez, H., Russell, W., Spain, L., Schatz, D. A., Sosenko, J., Wherrett, D., Wilson, D., Winter, W., Ziegler, A., Anderson, M., Antinozzi, P., Benoist, C., Blum, J., Bourcier, K., Chase, P., Clare-Salzler, M., Clynes, R., Cowie, C., Eisenbarth, G., Fathman, C. G., Grave, G., Harrison, L., Hering, B., Insel, R., Jordan, S., Kaufman, F., Kay, T., Kenyon, N., Klines, R., Lachin, J., Leschek, E., Mahon, J., Marks, J. B., Monzavi, R., Nanto-Salonen, K., Nepom, G., Orban, T., Parkman, R., Pescovitz, M., Peyman, J., Pugliese, A., Ridge, J., Roep, B., Roncarolo, M., Savage, P., Simell, O., Sherwin, R., Siegelman, M., Skyler, J. S., Thomas, J., Trucco, M., Wagner, J., Bourcier, K., Greenbaum, C. J., Krischer, J. P., Leschek, E., Rafkin, L., Spain, L., Cowie, C., Foulkes, M., Insel, R., Krause-Steinrauf, H., Lachin, J. M., Malozowski, S., Peyman, J., Ridge, J., Savage, P., Skyler, J. S., Zafonte, S. J., Greenbaum, C. J., Rafkin, L., Sosenko, J., Skyler, J. S., Kenyon, N. S., Santiago, I., Krischer, J. P., Bundy, B., Abbondondolo, M., Adams, T., Asif, D., Boonstra, M., Boulware, D., Bundy, B., Burroughs, C., Cuthbertson, D., Eberhard, C., Fiske, S., Ford, J., Garmeson, J., Guillette, H., Geyer, S., Hays, B., Henderson, C., Henry, M., Heyman, K., Hsiao, B., Karges, C., Kinderman, A., Lane, L., Leinbach, A., Liu, S., Lloyd, J., Malloy, J., Maddox, K., Martin, J., Miller, J., Moore, M., Muller, S., Nguyen, T., O'Donnell, R., Parker, M., Pereyra, M. J., Reed, N., Roberts, A., Sadler, K., Stavros, T., Tamura, R., Wood, K., Xu, P., Young, K., Alies, P., Badias, F., Baker, A., Bassi, M., Beam, C., Boulware, D., Bounmananh, L., Bream, S., Deemer, M., Freeman, D., Gough, J., Ginem, J., Granger, M., Holloway, M., Kieffer, M., Lane, P., Law, P., Linton, C., Nallamshetty, L., Oduah, V., Parrimon, Y., Paulus, K., Pilger, J., Ramiro, J., Ritzie, A., Sharma, A., Shor, A., Song, X., Terry, A., Weinberger, J., Wootten, M., Lachin, J. M., Harding, M., Krause-Steinrauf, H., McDonough, S., Mcgee, P. F., Hess, K., Phoebus, D., Quinlan, S., Raiden, E., Fradkin, J., Leschek, E., Spain, L., Cowie, C., Malozowski, S., Savage, P., Beck, G., Blumberg, E., Gubitosi-Klug, R., Laffel, L., Veatch, R., Wallace, D., Braun, J., Brillon, D., Lernmark, A., Lo, B., Mitchell, H., Naji, A., Nerup, J., Orchard, T., Steffes, M., Tsiatis, A., Zinman, B., Loechelt, B., Baden, L., Green, M., Weinberg, A., Marcovina, S., Palmer, J. P., Weinberg, A., Yu, L., Winter, W., Shultz, A., Batts, E., Fitzpatrick, K., Ramey, M., Guerra, R., Webb, C., Caffey, F., Carr, L., Ergun-Longmire, B., Fenton, C., Giebner, D., Johnson, J., Maglionico, D., Marinelli, M., Martin, K., Minnozzi, E., Riley, W., Wilson, M., Gougeon, C., Ho, J., Huang, C., Pacaud, D., Virtanen, H., Craig, C., Ghatak, A., Henderson, T., Leyland, H., Padmore, K., Paul, P., Brickman, W., Halsey-Lyda, M., Petrie, P., Rizzo, D., Steuer, R., Suchyta, K., Torchen, L., Zimmerman, D., Bode, B., Dial, M., Gazaway, K., Hosey, R., Alkanani, A., Barker, J., Barr, M., Blau, A., Burdick, P., Burke, B., Chase, H., Drye, M., Eisenbarth, G., Escobar, E., Fitzgerald-Miller, L., Fouts, A., Gage, V., Gall, E., Goettle, H., Gottlieb, P., Harris, S., Ketchum, K., King, M., Klingensmith, G., Lehr, D., Lehr, J., Lewis, L., Logsden-Sackett, N., Lykens, J., Maahs, D., Michels, A., Pelletier, S., Rihanek, M., Rodriguez, P., Schauwecker, A., Simmons, K., Smith, J., Steck, A., Tran, B., 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Haydock, H., Kennedy, K., Parker, V., Plimmer, N., Swart, L., Wood, C., Leyva, C., Padilla, J., Rodriguez, I., Ahmad, T., Bhatia, S., Conrad, S., Egli, C., Flores, B., Higa, A., Leong, K., Ng, V., Oakes, S., Olson, J., Blackmore, A., Bradley, B., Cooper, T., Courtney, J., Lawson, M., Richardson, C., Watson, C., Blind, J., Bowden, S., Bowen, B., Carter, K., Cecrle, M., Chaudhari, M., Cherko, J., Dyer, J., Ellis, K., Haines, J., Hapanowicz, C., Hardin, D., Henwood, M., Hoffman, R., Lamberjack, K., Leary, J., Lewis, S., Mhaskar, R., Rowe, S., Schoeginger, L., Stiltner, T., Bock, M., Castaneda, N., Fisher, L., Geffner, M., Gonzalez, M., Halvorson, M., Hisakado, M., Jeandron, D., Kaufman, F., Kwan, K., Marks, L., Medina, B., Miller, D., Monzavi, R., Ng, E., Parkman, R., Salazar, C., Tjauw, A., Wood, J., Woods, A., Xu, Y., Chalew, S., Daniels, J., Gomez, R., Lala, A., Layburn, S., Meyers, M., Sonnier, S., Valley, S., Ayala, N., Bhangoo, A., Bowen, S., Cervisi, J., Chase, Y., Clark, S., Daniels, M., Flannery, T., Forghani, N., Humphrey, L., Krause, G., Less, J., Lester, S., Magedman, G., Montgomery, K., Preasmyer, S., Quintana, R., Randhawa, R., Reh, C., Speer, H., Stockton, W., Sutton, F., Tran, A., Trihn, L., Tu, K., Varni, N., Ackermann, A., Capella, C., Clark, C., Gralewski, K., Hawkes, C., Kim, R., Katz, L., Liilii, R., McKenzie, O., Murphy, K., Norris, M., Orellana, J., Schwartzman, B., Sheth, S., Volpe, R., Willi, S., Healy, F., Heenan, H., Hodgman, S., Kendall, D., Logan, F., Lunt, H., Willis, J., Crimmins, N., Elder, D., Lagory, D., Schultz, C., Stamper, M., Weis, T., Armbruster, D., Klein, J., Konstantinopoulus, P., Latham, D., Markle, T., Mawhorter, C., Rizk, M., Rogers, D., Schmidt, N., Switzer, C., Bokor, L., DeMers, C., Pellizzari, M., Speiser, P., Clynes, R., Cook, S., Dinapoli, G., Eng, C., Engelman, H., Freeby, M., Gallagher, M., Gandica, R., Goland, R., Greenberg, E., Jezioro, J., Kurland, A., Leibel, N., Levine, E., Maher, C., Nieva, D., Parra, Z., 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Hildinger, M., Hufferd, R., Imel, E., Jagielo, B., Johnson, A., Johnson, N., Kost, B., Kruse, C., Laskowski, P., Leung, E., Mantravadi, M., Melvin, E., Mirmira, R., Mott, L., Mullen, M., Murphy, R., Nabhan, Z., Nebesio, T., Newnum, A., Nicholson-Spall, M., Patrick, V., Pfeiffer, J., Purtlebaugh, D., Rigby, M., Sanchez, J., Sims, E., Swan, E., Acharya, S., Garvey, L., Stormer, J., Bzdick, S., Conboy, P., Doolittle, S., Izquierdo, R., Sills, I., Weinstock, R., Alleyn, C., Baidal, D., Bryant, N., Conboy, D., Demanbey, A., Fay, S., Gaglia, J., Jackson, R., Jalahej, H., Koshy, N., Krishfield, S., Migre, M., Montero, M., Orban, T., Resnick, B., Ricker, A., Szubowicz, S., Turley, J., Weir, G., Wolfsdorf, J., Zhang, H., Balapatebendi, M., Barradell, A., Brunskill, C., Cheney, S., Greening, J., Hay, F., Hunt, S., Punniyakodi, S., Sikotra, N., Sundaram, P., Thanawala, N., Voce, R., Biggs, J., Faherty, A., Healy, F., Jefferies, C., Mannering, S., Prentis, R., Willis, J., Baskerville, T., 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J., Scaife, L., Vaidya, B., Walton-Salih, E., Whitmore, H., Wilkins, S., Wilkinson, L., Battaglia, M., Belloni, C., Bianconi, E., Bolla, A., Bonfanti, R., Bonopane, M., Bosi, E., Corti, M., Costa, S., Falqui, L., Fontana, B., Galluccio, E., Grogan, P., Laurenzi, A., Lombardoni, C., Martinenghi, S., Meschi, F., Molinari, C., Molteni, L., Monti, L., Pastore, M., Privitera, D., Ragogna, F., Spadoni, S., Stabilini, A., Vecchione, F., Viscardi, M., Al Nofal, A., Albers, D., Austad, S., Austin, S., Bartholow, L., Brantz-Miller, A., Broadbent, M., Brosnahan, J., Cortes, G., Coyne, C., Davis-Keppen, L., Griffin, K., Hahn, D., Hanisch, K., Hanson, D., Hauge, C., Hein, T., Howard, J., Huber, C., Johnson, J., Karmazin, A., Keller, L., Kirschbaum, S., Klinghagen, R., Krabbenhoft, B., Krell, E., Meier, J., Olson, C., Prenger, S., Sandman, C., Shelso, J., Springman, C., Thompson, M., Vandermark, J., Vanveldhuizen, A., Wurgler, J., Zimmerman, A., Alving, E., Benitez, S., Bryant, S., Cochrane, K., DiBlasi, C., Fechner, P., Gama, K., Harry, J., Jacob, S., Kearns, S., Klingsheim, M., Knutzen, S., Kong, A., Koves, I., Loots, B., Malik, F., Mano, E., Martinez, O., Nandi-Munshi, D., Ness, K., O'Connor, R., Pihoker, C., Roth, C., Salehi, P., Semana, S., Sexton, A., Taplin, C., Yaptangco, M., Bull, J., Gormley, S., Jones, K., Redfearn, K., Shackleton, J., Smith, H., Strong, L., Thomas, L., Viles, L., Wright, N., Kordel, J., Agardh, C., Ahlkvist, L., Ask, M., Berggren, S., Borg, H., Gerardsson, J., Gustavsson, B., Hakansson, R., Hansen, M., Hansson, G., Jarvirova, M., Jonsdottir, B., Katsarou, A., Kulinski, M., Larsson, H., Lernmark, A., Lind, A., Lindstrom, M., Lundgren, M., Massadakis, T., Melin, J., Mestan, Z., Mulder, H., Nilsson, C., Rosengren, A., Salami, F., Skarstrand, H., Tekum-Amboh, E., Torn, C., Ulvenhag, U., Wimar, A., Arthur, T., Buchanan, M., Cardoni, C., Christensen, R., Filicetti, M., Gerrard, X., Haven, K., Ioli, M., Jackson, J., Jones, E., Kauk, K., Koehler, B., Nihill, K., Parra, B., Russell, N., Schott, S., Tawney, L., Taylor, L., Waldren, C., Watsen, S., Whitham, L., Atkins, M., Aye, T., Bachrach, L., Baker, B., Barahona, K., Berry, B., Buckingham, B., Chau, C., Crossen, S., DeSalvo, D., Espinoza, O., Esrey, T., Kumar, R., Ly, T., Nally, L., Patel, P., Seeley, H., Shah, A., Shah, S., Soto, A., Stenerson, M., Wilson, D., Kioroglo, Y., Mann, C., Marlen, N., Nadgir, U., Olsen-Wilson, K., Prakasam, G., Bunk, M., Chmiel, R., Fischer, F., Gavrisan, A., Haupt, F., Heinrich, M., Herbst, M., Hivner, S., Hofelich, A., Holzmaier, M., Kriesen, Y., Lagoda, N., Loebner, S., Maison, N., Mau, E., Peplow, C., Puff, R., Ramminger, C., Sebelefsky, C., Walter, M., Warncke, K., Ziegler, A., Zillmer, S., Babar, G., Bedard, J., Bloom, K., Broussard, J., Bruce, C., Cernich, J., Clements, M., Clifton, T., Craig, E., Drees, A., Duprau, R., Feldt, M., Fridlington, A., Goodman, S., Hess, K., Hester, L., Huseman, C., Karmazin, A., Kim, E., King, A., Kover, K., Luetjen, T., Martin, K., McDonough, R., Moore, W., Musick, T., Newman, K., Nichols, C., Peterson, K., Raman, S., Reddig, N., Swiderski, S., Tong, P., Turpin, A., Turpin, A., Ugrasbul, F., Watkins, D., Weigel, S., Whisenhunt, M., Wierson, J., Wilcox, R., Wolfe, D., Zacharko, P., Zebley, J., Albini, C., Bethin, K., Borowski, R., Buchlis, J., Ecker, M., Elsinghorst, H., Fourtner, S., Gartner, L., Gorman, E., House, A., Kraengel, K., Krolczyk, A., Majumdar, I., Marrone, A., Mastrandrea, L., Michalovic, S., Musial, W., Quattrin, T., Russell, M., Rychlicki, L., Shelat, T., Shine, B., Sickau, J., Van der Kloet, E., Young, B., Ahenkorah, B., Balmer, D., Bedford, M., Cevallos, J., Chapman, K., De Lima, S., Duong, T., Eisel, L., Fiset, J., Harrington, J., Kovalakovska, R., Mehan, M., Nguyen, H., Perro, B., Ricci, M., Ricci, M., Roode, A., Sriskandarajah, M., Steger, R., Sultan, F., Wherrett, D., Aslanov, R., Crummell, C., Hagerty, D., Newhook, L., Penney, S., Stokes, J., Beck, J., Copeland, K., George, M., Larson, S., Less, J., Lopez, C., Roof, A., Schanuel, J., Sparling, D., Tryggestad, J., Lee, M., Shaw, B., Bobik, C., Bollepalli, S., Brownstein, R., Diamond, F., Eyth, E., Henson, D., Iyer, P., Jorgensen, V., Martin, J., Norman, J., O'Brian, J., Rodriguez, H., Shulman, D., Smith, L., Steinbrueck, J., Terry, A., Tindell, S., Garza, A., Grohman, C., Hale, D., Kral, J., Tragus, R., Word, D., Barrett, T., Holloway, S., Lighton, B., Morgan, R., Narendran, P., Smith, D., Ambrose, M., Chin, C., Durazo, G., Gonzalez-Garcia, Z., Gordon, M., Hollis, M., Senguttuvan, R., Stuehm, C., Wheeler, M., Aitken, R., Bingley, P., Castleden, H., Farthing, N., Hughes, T., Loud, S., Matthews, C., Mcgee, J., Morgan, A., Munoz, P., Pollitt, J., Pope, C., Rouquette, C., Thorne, B., Baynham, S., Gardiner, S., Genereaux, D., Jantzen, C., Lai, J., Lutley, P., Mammon, B., Membreve, J., Metzger, D., Morrison, K., Nguyen, D., Panagiotopoulos, C., Ronsley, C., Roston, A., Suen, J., Abalos, M., Adi, S., Anderson, M., Auerback, G., Berhel, A., Bomberg, E., Breen, K., Buchanan, J., Cook, A., Cakmak, A., Ferrara, C., Fields, S., Finney, Z., Fraser, K., Gonzalez, A., Ghods, S., Gitelman, S., Hamid, L., Hamilton, C., Hawkins, L., Honrada, R., Huang, A., Jain, A., Jossan, P., Ko, K., Larocque, N., Lilley, B., Long, R., Lustig, D. R., Ly, E., Malik, A., Melaku, A., Moassesfar, S., Mugg, A., Ng, D., Ng, D., O'Brien, C., Perez, E., Phelps, S., Prahalod, P., Ramos, E., Lugo, M., Rodriguez, T., Arao, A., Demeterco-Berggren, C., Duong, J., Gottschalk, M., Hashiguchi, M., Kelly, T., Marinkovic, M., Marois, N., Newfield, R., Phillips, S., Rosenblum, D., Abdullah, N., Dunger, D., Gilbert, A., Guy, C., Hendricks, E., May, J., O'Brien, C., Salgin, B., Thankamony, A., Vyse, N., Watts, A., Whitehead, K., Whitehead, L., Willemsen, R., Williams, R., Wingate, D., Devine, N., Gannon, G., Grant, T., Letourneau, L., Littlejohn, E., Norstrom, M., O'Malley, T., Philipson, L., Abraham, A., Agustin, E., Albanese-O'Neill, A., Beltz, S., Clare-Salzler, M., Cole, G., Cook, R., Coy, R., Ferguson, J., Ferguson, R., Haller, M., Hicks, E., Hosford, J., Jacobsen, L., Johnson, M., Kahler, D., Kerr, N., Kimsey, R., Lucas, A., Meehan, C., Paguio, G., Rohrs, H., Schatz, D., Smith, M., Thomas, J., Towe, P., White, D., Winter, W., Zimmerman, C., Hamalainen, J., Harkonen, T., Helander, S., Hero, M., Hirvasniemi, M., Isoaho, K., Jaminki, S., Joutsjoki, L., Kalliola, P., Kararic, M., Knip, M., Koski, K., Koski, M., Koski, M. L., Koskinen, M., Kytola, J., Laamanen, T., Latva-Koivisto, M., Laurinen, S., Mustila, T., Nyblom, M., Ollila, I., Pekkola, M., Salonen, K., Selvenius, J., Siljamaki, S., Siljander, H., Snygg, S., Suomalainen, H., Suomi, A., Tuomaala, A., Cabbage, J., Coffey, J., Hobbs, T., Johnson, K., Martin, M., Rosazza, S., Tansey, M., Tsalikian, E., Deuser, A., Foster, M., Pierce, G., Rayborn, L., Rodriguez-Luna, M., Rush, H., Wintergerst, K., Bloomfield, E., Catte, D., Dean, H., Ferens, H., Kerr, L., Kozak, B., Maharaj, R., Marks, S., Minuk, L., Rossum, K., Sneesby, K., Stierman, T., Sucharov-Benarroch, A., Taback, S., Woo, V., Yakimoski, A., Allende, G., Arazo, L., Arce, R., Baidal, D., Blaschke, C., Marks, J., Matheson, D., Pugliese, A., Sanders-Branca, N., Snowhite, I., Burant, C., Chen, M., Haddad, A., Herman, W., Hooks, H., Martin, C., Menon, R., Pietropaolo, M., Pietropaolo, S., Plunkett, C., Pop-Busui, R., Soleimanpour, A., Surhigh, J., Thomas, I., Wood, M., Bartyzal, A., Christianson, T., Flaherty, N., Forlenza, G., Gibson, C., Halper, A., Halvorsen, T., Hamdoun, E., Helms, H., Kwong, C., Lee, C., Leschyshyn, J., Luke, D., McVean, J., Moran, T., Nathan, B., Nelson, B., Omann, T., Pappenfus, B., Parchem, B., Storo, K., Street, A., Sunni, M., Tafuri, M., Vang, N., Weingartner, D., Becker, D., DeLallo, K., Diaz, A., Elnyczky, B., Groscost, D., Baldauff, N., Hoffmann, P., Ismail, H., Klein, M., Lamm, V., Libman, I., McDowell, K., Minshall, V., Pasek, B., Riley, K., Shelleby, C., Sigmund, L., Smith, M., Tas, E., Trucco, M., Yates, C., Artman, H., Johnson, B., Jospe, N., Miller, A., Orlowski, C., Jackson, M., Johnson, B., Knight, L., Szadek, L., Thompson, B., Welnick, G., Al-Zubeidi, H., Bansal, S., Bissler, M., Carroll, L., Cockroft, J., Dourisseau, D., Ferry, R., Foster, C., Johnson, T., Kassim, N., Lee, K., Logan, B., Mazhar, G., McCommon, D., Moisan, A., Parish, M., Sands, C., Sinha, S., Smith, L., Thomas, A., Thompson, L., Trzil, J., Wilson, N., Green, L., Harden, T., Kreymer, R., Mohan, A., Pruneda, M., Raskin, P., Richard, J., Schnurr-Breen, L., Smith, O., Sturges, D., Torres, N., Ziemian, L., Allred, M., Baker, S., Calder, T., Dansie, P., Donaldson, D., Foster, C., Garcia, E., Jarrett, K., Langvardt, J., Lener, M., Lusted, K., Murray, M., Reynolds, L., Slater, H., Thompson, D., Underlin, K., Vickers, L., Wheeler, K., Bere, L., Clarson, C., Gallego, P., Lovell, M., Mahon, J., McCallum, J., Stein, R., Babington, B., Barnes, K., Black, M., Bremer, A., Brendle, F., Brown, A., Dixon, B., Frazier, E., Gregg, A., Moore, D., Mountz, G., Olayinka, K., Pittel, E., Robertson, A., Russell, W., Shah, K., Shannon, A., Thomas, J., Yoder, S., Anderson, T., Bailey, D., Basnet, D., Branch, M., Bruce, G., Francis, G., Hagan, S., Henderson, G., Khandan-Barani, M., King, T., Le, T., Lemmons, J., Miller, M., Nesgoda, L., Penn, M., Schmid, J., Shankar, R., Usry, M., Wickham, E., Banks, W., Brown, H., Constantino, M., Hutson, J., Kellum, G., Lagarde, W., Lewis, M., Lockemer, H., McLaughlin, T., Piszczak, M., Reif, S., Vanderploeg, T., Andaloro, E., Breen, C., Colman, P., Dalgleish, N., Fourlanos, S., Gellert, S., Harrison, L., Healy, F., Hong, E., Hsieh, C., Mesfin, S., Mohammed, E., Redl, L., Watson, K., Wentworth, J., Cresswell, P., Faherty, H., Gould, A., Healy, F., Krebs, J., Maister, C., Ross, C., Wiltshire, E., Beresford, S., Campbell, S., Cortis, L., Couper, J., Cranwell, A., Fairchild, J., Healy, F., Richichi, K., Abdelghany, O., Feldman, L., Forbes, N., Herold, K., Huang, Y., Kunze, K., Rink, L., Sherr, J., Sherwin, R., Tamborlane, W., Weinzimer, S., Wurtz, A., Yama, N., Young, L., Writing Comm Type Diabet 2017; 318 (19): 1891–1902

    Abstract

    Type 1 diabetes requires major lifestyle changes and carries increased morbidity and mortality. Prevention or delay of diabetes would have major clinical effect.To determine whether oral insulin delays onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes.Between March 2, 2007, and December 21, 2015, relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance, were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany. The main study group (n = 389) had first-phase insulin release on an intravenous glucose tolerance test that was higher than the threshold. The 55 patients in the secondary stratum 1 had an identical antibody profile as the main study group except they had first-phase insulin release that was lower than the threshold. Secondary strata 2 (n = 114) and strata 3 (n = 3) had different autoantibody profiles and first-phase insulin release threshold combinations. Follow-up continued through December 31, 2016.Randomization to receive 7.5 mg/d of oral insulin (n = 283) or placebo (n = 277), including participants in the main study group who received oral insulin (n = 203) or placebo (n = 186).The primary outcome was time to diabetes in the main study group. Significance was based on a 1-sided threshold of .05, and 1-sided 95% CIs are reported.Of a total of 560 randomized participants (median enrollment age, 8.2 years; interquartile range [IQR], 5.7-12.1 years; 170 boys [60%]; 90.7% white non-Hispanic; 57.6% with a sibling with type 1 diabetes), 550 completed the trial including 389 participants (median age, 8.4 years; 245 boys [63%]), 382 (96%) in the main study group. During a median follow-up of 2.7 years (IQR, 1.5-4.6 years) in the main study group, diabetes was diagnosed in 58 participants (28.5%) in the oral insulin group and 62 (33%) in the placebo group. Time to diabetes was not significantly different between the 2 groups (hazard ratio [HR], 0.87; 95% CI, 0-1.2; P = .21). In secondary stratum 1 (n = 55), diabetes was diagnosed in 13 participants (48.1%) in the oral insulin group and in 19 participants (70.3%) in the placebo group. The time to diabetes was significantly longer with oral insulin (HR, 0.45; 95% CI, 0-0.82; P = .006). The HR for time to diabetes for the between-group comparisons for the 116 participants in the other secondary stratum was 1.03 (95% CI, 0-2.11; P = .53) and for the entire cohort of 560 participants was 0.83 (95% CI, 0-1.07; P = .11), which were not significantly different. The most common adverse event was infection (n = 254), with 134 events in the oral insulin group and 120 events in the placebo group, but no significant study-related adverse events occurred.Among autoantibody-positive relatives of patients with type 1 diabetes, oral insulin at a dose of 7.5 mg/d, compared with placebo, did not delay or prevent the development of type 1 diabetes over 2.7 years. These findings do not support oral insulin as used in this study for diabetes prevention.clinicaltrials.gov Identifier: NCT00419562.

    View details for DOI 10.1001/jama.2017.17070

    View details for Web of Science ID 000415870300019

    View details for PubMedID 29164254

    View details for PubMedCentralID PMC5798455

  • A Meta Genome-Wide Association Study Identifies a Novel Locus for Cardiovascular Disease in Type 1 Diabetes Keshavarzi, S., Canty, A., Klein, B. K., Trevor, O. J., Costacou, T., Klein, R., Snell-Bergeon, J., Maahs, D., Miller, R., Lee, K. E., Paterson, A. D. WILEY. 2017: 657–58
  • Application of Zone Model Predictive Control Artificial Pancreas During Extended Use of Infusion Set and Sensor: A Randomized Crossover-Controlled Home-Use Trial. Diabetes care Forlenza, G. P., Deshpande, S., Ly, T. T., Howsmon, D. P., Cameron, F., Baysal, N., Mauritzen, E., Marcal, T., Towers, L., Bequette, B. W., Huyett, L. M., Pinsker, J. E., Gondhalekar, R., Doyle, F. J., Maahs, D. M., Buckingham, B. A., Dassau, E. 2017

    Abstract

    As artificial pancreas (AP) becomes standard of care, consideration of extended use of insulin infusion sets (IIS) and continuous glucose monitors (CGMs) becomes vital. We conducted an outpatient randomized crossover study to test the safety and efficacy of a zone model predictive control (zone-MPC)-based AP system versus sensor augmented pump (SAP) therapy in which IIS and CGM failures were provoked via extended wear to 7 and 21 days, respectively.A smartphone-based AP system was used by 19 adults (median age 23 years [IQR 10], mean 8.0 ± 1.7% HbA1c) over 2 weeks and compared with SAP therapy for 2 weeks in a crossover, unblinded outpatient study with remote monitoring in both study arms.AP improved percent time 70-140 mg/dL (48.1 vs. 39.2%; P = 0.016) and time 70-180 mg/dL (71.6 vs. 65.2%; P = 0.008) and decreased median glucose (141 vs. 153 mg/dL; P = 0.036) and glycemic variability (SD 52 vs. 55 mg/dL; P = 0.044) while decreasing percent time <70 mg/dL (1.3 vs. 2.7%; P = 0.001). AP also improved overnight control, as measured by mean glucose at 0600 h (140 vs. 158 mg/dL; P = 0.02). IIS failures (1.26 ± 1.44 vs. 0.78 ± 0.78 events; P = 0.13) and sensor failures (0.84 ± 0.6 vs. 1.1 ± 0.73 events; P = 0.25) were similar between AP and SAP arms. Higher percent time in closed loop was associated with better glycemic outcomes.Zone-MPC significantly and safely improved glycemic control in a home-use environment despite prolonged CGM and IIS wear. This project represents the first home-use AP study attempting to provoke and detect component failure while successfully maintaining safety and effective glucose control.

    View details for DOI 10.2337/dc17-0500

    View details for PubMedID 28584075

  • Prevalence of Celiac Disease in 52,721 Youth With Type 1 Diabetes: International Comparison Across Three Continents. Diabetes care Craig, M. E., Prinz, N., Boyle, C. T., Campbell, F. M., Jones, T. W., Hofer, S. E., Simmons, J. H., Holman, N., Tham, E., Fröhlich-Reiterer, E., Dubose, S., Thornton, H., King, B., Maahs, D. M., Holl, R. W., Warner, J. T. 2017

    Abstract

    Celiac disease (CD) has a recognized association with type 1 diabetes. We examined international differences in CD prevalence and clinical characteristics of youth with coexisting type 1 diabetes and CD versus type 1 diabetes only.Data sources were as follows: the Prospective Diabetes Follow-up registry (Germany/Austria); the T1D Exchange Clinic Network (T1DX) (U.S.); the National Paediatric Diabetes Audit (U.K. [England/Wales]); and the Australasian Diabetes Data Network (ADDN) (Australia). The analysis included 52,721 youths <18 years of age with a clinic visit between April 2013 and March 2014. Multivariable linear and logistic regression models were constructed to analyze the relationship between outcomes (HbA1c, height-standard deviation score [SDS], overweight/obesity) and type 1 diabetes/CD versus type 1 diabetes, adjusting for sex, age, and diabetes duration.Biopsy-confirmed CD was present in 1,835 youths (3.5%) and was diagnosed at a median age of 8.1 years (interquartile range 5.3-11.2 years). Diabetes duration at CD diagnosis was <1 year in 37% of youths, >1-2 years in 18% of youths, >3-5 years in 23% of youths, and >5 years in 17% of youths. CD prevalence ranged from 1.9% in the T1DX to 7.7% in the ADDN and was higher in girls than boys (4.3% vs. 2.7%, P < 0.001). Children with coexisting CD were younger at diabetes diagnosis compared with those with type 1 diabetes only (5.4 vs. 7.0 years of age, P < 0.001) and fewer were nonwhite (15 vs. 18%, P < 0.001). Height-SDS was lower in those with CD (0.36 vs. 0.48, adjusted P < 0.001) and fewer were overweight/obese (34 vs. 37%, adjusted P < 0.001), whereas mean HbA1c values were comparable: 8.3 ± 1.5% (67 ± 17 mmol/mol) versus 8.4 ± 1.6% (68 ± 17 mmol/mol).CD is a common comorbidity in youth with type 1 diabetes. Differences in CD prevalence may reflect international variation in screening and diagnostic practices, and/or CD risk. Although glycemic control was not different, the lower height-SDS supports close monitoring of growth and nutrition in this population.

    View details for DOI 10.2337/dc16-2508

    View details for PubMedID 28546222

  • Clinical Use of Continuous Glucose Monitoring in Pediatrics. Diabetes technology & therapeutics Lal, R. A., Maahs, D. M. 2017; 19 (S2): S37-S43

    View details for DOI 10.1089/dia.2017.0013

    View details for PubMedID 28541138

  • Outpatient Closed-Loop Control with Unannounced Moderate Exercise in Adolescents Using Zone Model Predictive Control. Diabetes technology & therapeutics Huyett, L. M., Ly, T. T., Forlenza, G. P., Reuschel-DiVirgilio, S., Messer, L. H., Wadwa, R. P., Gondhalekar, R., Doyle, F. J., Pinsker, J. E., Maahs, D. M., Buckingham, B. A., Dassau, E. 2017

    Abstract

    The artificial pancreas (AP) has the potential to improve glycemic control in adolescents. This article presents the first evaluation in adolescents of the Zone Model Predictive Control and Health Monitoring System (ZMPC+HMS) AP algorithms, and their first evaluation in a supervised outpatient setting with frequent exercise.Adolescents with type 1 diabetes underwent 3 days of closed-loop control (CLC) in a hotel setting with the ZMPC+HMS algorithms on the Diabetes Assistant platform. Subjects engaged in twice-daily exercise, including soccer, tennis, and bicycling. Meal size (unrestricted) was estimated and entered into the system by subjects to trigger a bolus, but exercise was not announced.Ten adolescents (11.9-17.7 years) completed 72 h of CLC, with data on 95 ± 14 h of sensor-augmented pump (SAP) therapy before CLC as a comparison to usual therapy. The percentage of time with continuous glucose monitor (CGM) 70-180 mg/dL was 71% ± 10% during CLC, compared to 57% ± 16% during SAP (P = 0.012). Nocturnal control during CLC was safe, with 0% (0%, 0.6%) of time with CGM <70 mg/dL compared to 1.1% (0.0%, 14%) during SAP. Despite large meals (estimated up to 120 g carbohydrate), only 8.0% ± 6.9% of time during CLC was spent with CGM >250 mg/dL (16% ± 14% during SAP). The system remained connected in CLC for 97% ± 2% of the total study time. No adverse events or severe hypoglycemia occurred.The use of the ZMPC+HMS algorithms is feasible in the adolescent outpatient environment and achieved significantly more time in the desired glycemic range than SAP in the face of unannounced exercise and large announced meal challenges.

    View details for DOI 10.1089/dia.2016.0399

    View details for PubMedID 28459617

  • Dietary intake and risk of non-severe hypoglycemia in adolescents with type 1 diabetes. Journal of diabetes and its complications Zhong, V. W., Crandell, J. L., Shay, C. M., Gordon-Larsen, P., Cole, S. R., Juhaeri, J., Kahkoska, A. R., Maahs, D. M., Seid, M., Forlenza, G. P., Mayer-Davis, E. J. 2017

    Abstract

    To determine the association between dietary intake and risk of non-severe hypoglycemia in adolescents with type 1 diabetes.Type 1 adolescents from a randomized trial wore a blinded continuous glucose monitoring (CGM) system at baseline for one week in free-living conditions. Dietary intake was calculated as the average from two 24-h dietary recalls. Non-severe hypoglycemia was defined as having blood glucose <70mg/dL for ≥10min but not requiring external assistance, categorized as daytime and nocturnal (11PM-7AM). Data were analyzed using logistic regression models.Among 98 participants with 14,277h of CGM data, 70 had daytime hypoglycemia, 66 had nocturnal hypoglycemia, 55 had both, and 17 had neither. Soluble fiber and protein intake were positively associated with both daytime and nocturnal hypoglycemia. Glycemic index, monounsaturated fat, and polyunsaturated fat were negatively associated with daytime hypoglycemia only. Adjusting for total daily insulin dose per kilogram eliminated all associations.Dietary intake was differentially associated with daytime and nocturnal hypoglycemia. Over 80% of type 1 adolescents had hypoglycemia in a week, which may be attributed to the mismatch between optimal insulin dose needed for each meal and actually delivered insulin dose without considering quality of carbohydrate and nutrients beyond carbohydrate.ClinicalTrials.gov identifier: NCT01286350.

    View details for DOI 10.1016/j.jdiacomp.2017.04.017

    View details for PubMedID 28476567

  • Expectations and Attitudes of Individuals With Type 1 Diabetes After Using a Hybrid Closed Loop System DIABETES EDUCATOR Iturralde, E., Tanenbaum, M. L., Hanes, S. J., Suttiratana, S. C., Ambrosino, J. M., Ly, T. T., Maahs, D. M., Naranjo, D., Walders-Abramson, N., Weinzimer, S. A., Buckingham, B. A., Hood, K. K. 2017; 43 (2): 223-232

    Abstract

    Purpose The first hybrid closed loop (HCL) system, which automates insulin delivery but requires user inputs, was approved for treatment of type 1 diabetes (T1D) by the US Food and Drug Administration in September 2016. The purpose of this study was to explore the benefits, expectations, and attitudes of individuals with T1D following a clinical trial of an HCL system. Methods Thirty-two individuals with T1D (17 adults, 15 adolescents) participated in focus groups after 4 to 5 days of system use. Content analysis generated themes regarding perceived benefits, hassles, and limitations. Results Some participants felt misled by terms such as "closed loop" and "artificial pancreas," which seemed to imply a more "hands-off" experience. Perceived benefits were improved glycemic control, anticipated reduction of long-term complications, better quality of life, and reduced mental burden of diabetes. Hassles and limitations included unexpected tasks for the user, difficulties wearing the system, concerns about controlling highs, and being reminded of diabetes. Conclusion Users are willing to accept some hassles and limitations if they also perceive health and quality-of-life benefits beyond current self-management. It is important for clinicians to provide a balanced view of positives and negatives to help manage expectations.

    View details for DOI 10.1177/0145721717697244

    View details for Web of Science ID 000397980900009

    View details for PubMedID 28340542

  • Prediction of acute coronary syndromes by urinary proteome analysis PLOS ONE Htun, N. M., Magliano, D. J., Zhang, Z., Lyons, J., Petit, T., Nkuipou-Kenfack, E., Ramirez-Torres, A., von zur Muhlen, C., Maahs, D., Schanstra, J. P., Pontillo, C., Pejchinovski, M., Snell-Bergeon, J. K., Delles, C., Mischak, H., Staessen, J. A., Shaw, J. E., Koeck, T., Peter, K. 2017; 12 (3)

    Abstract

    Identification of individuals who are at risk of suffering from acute coronary syndromes (ACS) may allow to introduce preventative measures. We aimed to identify ACS-related urinary peptides, that combined as a pattern can be used as prognostic biomarker. Proteomic data of 252 individuals enrolled in four prospective studies from Australia, Europe and North America were analyzed. 126 of these had suffered from ACS within a period of up to 5 years post urine sampling (cases). Proteomic analysis of 84 cases and 84 matched controls resulted in the discovery of 75 ACS-related urinary peptides. Combining these to a peptide pattern, we established a prognostic biomarker named Acute Coronary Syndrome Predictor 75 (ACSP75). ACSP75 demonstrated reasonable prognostic discrimination (c-statistic = 0.664), which was similar to Framingham risk scoring (c-statistics = 0.644) in a validation cohort of 42 cases and 42 controls. However, generating by a composite algorithm named Acute Coronary Syndrome Composite Predictor (ACSCP), combining the biomarker pattern ACSP75 with the previously established urinary proteomic biomarker CAD238 characterizing coronary artery disease as the underlying aetiology, and age as a risk factor, further improved discrimination (c-statistic = 0.751) resulting in an added prognostic value over Framingham risk scoring expressed by an integrated discrimination improvement of 0.273 ± 0.048 (P < 0.0001) and net reclassification improvement of 0.405 ± 0.113 (P = 0.0007). In conclusion, we demonstrate that urinary peptide biomarkers have the potential to predict future ACS events in asymptomatic patients. Further large scale studies are warranted to determine the role of urinary biomarkers in clinical practice.

    View details for DOI 10.1371/journal.pone.0172036

    View details for Web of Science ID 000396073700065

    View details for PubMedID 28273075

  • Predictive Hyperglycemia and Hypoglycemia Minimization: In-Home Evaluation of Safety, Feasibility, and Efficacy in Overnight Glucose Control in Type 1 Diabetes. Diabetes care Spaic, T., Driscoll, M., Raghinaru, D., Buckingham, B. A., Wilson, D. M., Clinton, P., Chase, H. P., Maahs, D. M., Forlenza, G. P., Jost, E., Hramiak, I., Paul, T., Bequette, B. W., Cameron, F., Beck, R. W., Kollman, C., Lum, J. W., Ly, T. T. 2017; 40 (3): 359-366

    Abstract

    The objective of this study was to determine the safety, feasibility, and efficacy of a predictive hyperglycemia and hypoglycemia minimization (PHHM) system compared with predictive low-glucose insulin suspension (PLGS) alone in overnight glucose control.A 42-night trial was conducted in 30 individuals with type 1 diabetes in the age range 15-45 years. Participants were randomly assigned each night to either PHHM or PLGS and were blinded to the assignment. The system suspended the insulin pump on both the PHHM and PLGS nights for predicted hypoglycemia but delivered correction boluses for predicted hyperglycemia on PHHM nights only. The primary outcome was the percentage of time spent in a sensor glucose range of 70-180 mg/dL during the overnight period.The addition of automated insulin delivery with PHHM increased the time spent in the target range (70-180 mg/dL) from 71 ± 10% during PLGS nights to 78 ± 10% during PHHM nights (P < 0.001). The average morning blood glucose concentration improved from 163 ± 23 mg/dL after PLGS nights to 142 ± 18 mg/dL after PHHM nights (P < 0.001). Various sensor-measured hypoglycemic outcomes were similar on PLGS and PHHM nights. All participants completed 42 nights with no episodes of severe hypoglycemia, diabetic ketoacidosis, or other study- or device-related adverse events.The addition of a predictive hyperglycemia minimization component to our existing PLGS system was shown to be safe, feasible, and effective in overnight glucose control.

    View details for DOI 10.2337/dc16-1794

    View details for PubMedID 28100606

    View details for PubMedCentralID PMC5319476

  • Diabetes Technology and Therapy in the Pediatric Age Group. Diabetes technology & therapeutics Maahs, D. M., Shalitin, S. 2017; 19 (S1): S105-S119

    View details for DOI 10.1089/dia.2017.2510

    View details for PubMedID 28192027

  • Albuminuria is associated with greater copeptin concentrations in men with type 1 diabetes: A brief report from the T1D exchange Biobank. Journal of diabetes and its complications Bjornstad, P., Johnson, R. J., Snell-Bergeon, J. K., Pyle, L., Davis, A., Foster, N., Cherney, D. Z., Maahs, D. M. 2017; 31 (2): 387-389

    Abstract

    Vasopressin exerts important cardio-renal effects, but remains problematic to measure. Copeptin is a more stable peptide derived from the same precursor molecule. In this case-control study from the Type 1 Diabetes Exchange (T1DX) Biobank registry, men with T1D and albuminuria had greater copeptin concentrations than men with normoalbuminuria.

    View details for DOI 10.1016/j.jdiacomp.2016.11.015

    View details for PubMedID 27979439

    View details for PubMedCentralID PMC5303164

  • Adiponectin is associated with early diabetic kidney disease in adults with type 1 diabetes: A Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study JOURNAL OF DIABETES AND ITS COMPLICATIONS Bjornstad, P., Pyle, L., Kinney, G. L., Rewers, M., Johnson, R. J., Maahs, D. M., Snell-Bergeon, J. K. 2017; 31 (2): 369-374
  • Predictors of Dyslipidemia Over Time in Youth With Type 1 Diabetes: For the SEARCH for Diabetes in Youth Study. Diabetes care Shah, A. S., Maahs, D. M., Stafford, J. M., Dolan, L. M., Lang, W., Imperatore, G., Bell, R. A., Liese, A. D., Reynolds, K., Pihoker, C., Marcovina, S., D'Agostino, R. B., Dabelea, D. 2017

    Abstract

    Understanding the risk factors associated with progression and regression of dyslipidemia in youth with type 1 diabetes may guide treatments.We studied 1,478 youth with type 1 diabetes (age 10.8 ± 3.9 years, 50% male, 77% non-Hispanic white, not on lipid-lowering medications) at baseline and at a mean follow-up of 7.1 ± 1.9 years in the SEARCH for Diabetes in Youth (SEARCH) study. Progression to dyslipidemia was defined as normal lipid concentrations at baseline and abnormal at follow-up (non-HDL-cholesterol [C] >130 mg/dL or HDL-C <35 mg/dL). Regression was defined as abnormal lipids at baseline and normal at follow-up. Multivariable logistic regression was used to evaluate factors associated with progression and regression compared with stable normal and stable abnormal, respectively. An area under the curve (AUC) variable was used for the time-varying covariates A1C and waist-to-height ratio (WHtR).Non-HDL-C progressed, regressed, was stable normal, and stable abnormal in 19%, 5%, 69%, and 7% of youth with type 1 diabetes, respectively. Corresponding percentages for HDL-C were 3%, 3%, 94%, and 1%, respectively. Factors associated with non-HDL-C progression were higher A1C AUC and higher WHtR AUC in males. Non-HDL-C regression was associated with lower WHtR AUC, and HDL-C progression was associated with male sex and higher WHtR AUC. HDL-C regression was not modeled due to small numbers.A1C and WHtR are modifiable risk factors associated with change in dyslipidemia over time in youth with type 1 diabetes.

    View details for DOI 10.2337/dc16-2193

    View details for PubMedID 28126715

    View details for PubMedCentralID PMC5360282

  • Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women. Pediatric diabetes Levenson, A. E., Shah, A. S., Khoury, P. R., Kimball, T. R., Urbina, E. M., de Ferranti, S. D., Maahs, D. M., Dolan, L. M., Wadwa, R. P., Biddinger, S. B. 2017

    Abstract

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol and cardiovascular disease risk, and is an emerging therapeutic target.We compared serum PCSK9 levels in young adults, with and without type 2 diabetes.Cross-sectional analysis was conducted in a cohort, aged 15 to 26 years, in Cincinnati, OH, from 2005 to 2010. Serum PCSK9 levels were measured in 94 youth with type 2 diabetes, 93 obese control subjects, and 99 lean control subjects. Correlative analyses were conducted to determine significant covariates of PCSK9 by group and sex, and multivariate linear regression models were used to study the independent determinants of PCSK9.In females, PCSK9 levels were significantly increased in the obese and type 2 diabetes subjects relative to the lean controls (P < .01). Moreover, PCSK9 was positively correlated with multiple metabolic parameters in females: body mass index, systolic blood pressure, fasting glucose, fasting insulin, and C-reactive protein levels (P ≤ .02). In males, PCSK9 levels were decreased overall compared with females (P = .03), and did not differ between the lean, obese, or type 2 diabetes groups.Obesity and type 2 diabetes were associated with significantly higher levels of PCSK9 in young women, but not in young men. These data suggest that sex could modify the effects of obesity and diabetes on PCSK9 in young adults.

    View details for DOI 10.1111/pedi.12490

    View details for PubMedID 28093849

  • Obese adolescents with polycystic ovarian syndrome have elevated cardiovascular disease risk markers. Vascular medicine Patel, S. S., Truong, U., King, M., Ferland, A., Moreau, K. L., Dorosz, J., Hokanson, J. E., Wang, H., Kinney, G. L., Maahs, D. M., Eckel, R. H., Nadeau, K. J., Cree-Green, M. 2017: 1358863X16682107-?

    Abstract

    Women with polycystic ovarian syndrome (PCOS) have evidence of subclinical cardiovascular disease (CVD). However, insulin resistance, an important factor in the development of CVD in adults, is common in adolescents with PCOS, yet data in adolescents are limited. Therefore, we sought to measure insulin resistance and CVD markers in obese youth with and without PCOS. Thirty-six PCOS and 17 non-PCOS adolescent girls who were obese, sedentary, and non-hypertensive were recruited from clinics located within the Children's Hospital Colorado. Following 3 days of controlled diet and restricted exercise, fasting plasma samples were obtained prior to a hyperinsulinemic euglycemic clamp. PCOS girls were more insulin resistant than controls (glucose infusion rate 5.24±1.86 mg/kg/min vs 9.10±2.69; p<0.001). Girls with PCOS had blood pressure in the normal range, but had greater carotid intima-media thickness (cIMT) (0.49±0.07 mm vs 0.44±0.06; p=0.038), beta stiffness index (5.1±1.3 U vs 4.4±0.9; p=0.037), and reduced arterial compliance (1.95±0.47 mm(2)/mmHg × 10(-1) vs 2.13±0.43; p=0.047). PCOS girls had a normal mean lipid profile, yet had a more atherogenic lipoprotein cholesterol distribution and had persistent elevations of free fatty acids despite hyperinsulinemia (68±28 μmol/mL vs 41±10; p=0.001), both potential contributors to CVD. Free fatty acid concentrations correlated best with all CVD markers. In summary, adolescent girls with PCOS have greater cIMT and stiffer arteries than girls without PCOS, perhaps related to altered lipid metabolism, even when clinical measures of blood pressure and cholesterol profiles are 'normal'. Therefore, management of adolescent PCOS should include assessment of CVD risk factor development.

    View details for DOI 10.1177/1358863X16682107

    View details for PubMedID 28095749

  • Biopsychosocial Aspects of Weight Management in Type 1 Diabetes: a Review and Next Steps. Current diabetes reports Driscoll, K. A., Corbin, K. D., Maahs, D. M., Pratley, R., Bishop, F. K., Kahkoska, A., Hood, K. K., Mayer-Davis, E. 2017; 17 (8): 58

    Abstract

    This review aims to summarize the type 1 diabetes (T1D) and weight literature with an emphasis on barriers associated with weight management, the unique T1D-specific factors that impact weight loss success, maladaptive and adaptive strategies for weight loss, and interventions to promote weight loss.Weight gain is associated with intensive insulin therapy. Overweight and obese weight status in individuals with T1D is higher than the general population and prevalence is rising. A variety of demographic (e.g., female sex), clinical (e.g., greater insulin needs), environmental (e.g., skipping meals), and psychosocial (e.g., depression, stress) factors are associated with overweight/obese weight status in T1D. Fear of hypoglycemia is a significant barrier to engagement in physical activity. Studies evaluating adaptive weight loss strategies in people with T1D are limited. There is a growing literature highlighting the prevalence and seriousness of overweight and obesity among both youth and adults with T1D. There is an urgent need to develop evidence-based weight management guidelines and interventions that address the unique concerns of individuals with T1D and that concurrently address glycemic control.

    View details for DOI 10.1007/s11892-017-0892-1

    View details for PubMedID 28660565

  • Serum cystatin C in youth with diabetes: The SEARCH for diabetes in youth study. Diabetes research and clinical practice Kanakatti Shankar, R., Dolan, L. M., Isom, S., Saydah, S., Maahs, D. M., Dabelea, D., Reynolds, K., Hirsch, I. B., Rodriguez, B. L., Mayer-Davis, E. J., Marcovina, S., D'Agostino, R., Mauer, M., Mottl, A. K. 2017; 130: 258–65

    Abstract

    We compared cystatin C in youth with versus without diabetes and determined factors associated with cystatin C in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D).Youth (ages 12-19years) without diabetes (N=544) were ascertained from the NHANES Study 2000-2002 and those with T1D (N=977) and T2D (N=168) from the SEARCH for Diabetes in Youth Study. Adjusted means of cystatin C concentrations were compared amongst the 3 groups. Next, we performed multivariable analyses within the T1D and T2D SEARCH samples to determine the association between cystatin C and race, sex, age, diabetes duration, HbA1c, fasting glucose, and BMI.Adjusted cystatin C concentrations were statistically higher in NHANES (0.85mg/L) than in either the T1D (0.75mg/L) or T2D (0.70mg/L) SEARCH groups (P<0.0001). Fasting glucose was inversely related to cystatin C only in T1D (P<0.001) and BMI positively associated only in T2D (P<0.01) while HbA1c was inversely associated in both groups.Cystatin C concentrations are statistically higher in youth without diabetes compared to T1D or T2D, however the clinical relevance of this difference is quite small, especially in T1D. In youth with diabetes, cystatin C varies with BMI and acute and chronic glycemic control, however their effects may be different according to diabetes type.

    View details for DOI 10.1016/j.diabres.2017.06.010

    View details for PubMedID 28666182

    View details for PubMedCentralID PMC5575920

  • Closed-Loop Control Without Meal Announcement in Type 1 Diabetes. Diabetes technology & therapeutics Cameron, F. M., Ly, T. T., Buckingham, B. A., Maahs, D. M., Forlenza, G. P., Levy, C. J., Lam, D., Clinton, P., Messer, L. H., Westfall, E., Levister, C., Xie, Y. Y., Baysal, N., Howsmon, D., Patek, S. D., Bequette, B. W. 2017; 19 (9): 527–32

    Abstract

    A fully closed-loop insulin-only system was developed to provide glucose control in patients with type 1 diabetes without requiring announcement of meals or activity. Our goal was to assess initial safety and efficacy of this system.The multiple model probabilistic controller (MMPPC) anticipates meals when the patient is awake. The controller used the subject's basal rates and total daily insulin dose for initialization. The system was tested at two sites on 10 patients in a 30-h inpatient study, followed by 15 subjects at three sites in a 54-h supervised hotel study, where the controller was challenged by exercise and unannounced meals. The system was implemented on the UVA DiAs system using a Roche Spirit Combo Insulin Pump and a Dexcom G4 Continuous Glucose Monitor.The mean overall (24-h basis) and nighttime (11 PM-7 AM) continuous glucose monitoring (CGM) values were 142 and 125 mg/dL during the inpatient study. The hotel study used a different daytime tuning and manual announcement, instead of automatic detection, of sleep and wake periods. This resulted in mean overall (24-h basis) and nighttime CGM values of 152 and 139 mg/dL for the hotel study and there was also a reduction in hypoglycemia events from 1.6 to 0.91 events/patient/day.The MMPPC system achieved a mean glucose that would be particularly helpful for people with an elevated A1c as a result of frequent missed meal boluses. Current full closed loop has a higher risk for hypoglycemia when compared with algorithms using meal announcement.

    View details for DOI 10.1089/dia.2017.0078

    View details for PubMedID 28767276

    View details for PubMedCentralID PMC5647490

  • Predictors of early renal function decline in adults with Type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes and the Pittsburgh Epidemiology of Diabetes Complications studies. Diabetic medicine : a journal of the British Diabetic Association Bjornstad, P., Costacou, T., Miller, R. G., Maahs, D. M., Rewers, M. J., Orchard, T. J., Snell-Bergeon, J. K. 2017; 34 (11): 1532–40

    Abstract

    Diabetic kidney disease is one of the leading complications of Type 1 diabetes, but its prediction remains a challenge. We examined predictors of rapid decline in estimated GFR (eGFR) in two Type 1 diabetes cohorts: the Coronary Artery Calcification in Type 1 Diabetes (CACTI) and the Pittsburgh Epidemiology of Diabetes Complications (EDC).A select subset of participants (CACTI: n = 210 and EDC: n = 98) diagnosed before 17 years of age with Type 1 diabetes duration ≥ 7 years, and follow-up data on eGFR by CKD-EPI creatinine for up to 8 years were included in the analyses. Early renal function decline was defined as annual decline in eGFR ≥ 3 ml/min/1.73 m2, and normal age-related decline as eGFR ≤ 1 ml/min/1.73 m2. Parallel logistic regression models were constructed in the two cohorts.Early renal function decline incidence was 36% in CACTI and 41% in EDC. In both cohorts, greater baseline eGFR (CACTI: OR 3.12, 95% CI 1.97-5.05; EDC: OR 1.92, 95% CI 1.17-3.15 per 10 ml/min/1.73 m2) and log albumin-to-creatinine (ACR) (CACTI: OR 3.24, 95% CI 1.80-5.83; EDC: OR 1.87, 95% CI 1.18-2.96 per 1 unit) predicted greater odds of early renal function decline in fully adjusted models. Conversely, ACE inhibition predicted lower odds of early renal function decline in women in CACTI, but similar relationships were not observed in women in EDC.A substantial proportion of people with Type 1 diabetes in the EDC and CACTI cohorts experienced early renal function decline over time. ACE inhibition appeared to be protective only in women in CACTI where the prevalence of its use was twofold higher compared with the EDC.

    View details for DOI 10.1111/dme.13430

    View details for PubMedID 28734104

    View details for PubMedCentralID PMC5647234

  • Behavioural implications of traditional treatment and closed-loop automated insulin delivery systems in Type 1 diabetes: applying a cognitive restraint theory framework. Diabetic medicine : a journal of the British Diabetic Association Kahkoska, A. R., Mayer-Davis, E. J., Hood, K. K., Maahs, D. M., Burger, K. S. 2017; 34 (11): 1500–1507

    Abstract

    As the prevalence of obesity in Type 1 diabetes rises, the effects of emerging therapy options should be considered in the context of both weight and glycaemic control outcomes. Artificial pancreas device systems will 'close the loop' between blood glucose monitoring and automated insulin delivery and may transform day-to-day dietary management for people with Type 1 diabetes in multiple ways. In the present review, we draw directly from cognitive restraint theory to consider unintended impacts that closed-loop systems may have on ingestive behaviour and food intake. We provide a brief overview of dietary restraint theory and its relation to weight status in the general population, discuss the role of restraint in traditional Type 1 diabetes treatment, and lastly, use this restraint framework to discuss the possible behavioural implications and opportunities of closed-loop systems in the treatment of Type 1 diabetes. We hypothesize that adopting closed-loop systems will lift the diligence and restriction that characterizes Type 1 diabetes today, thus requiring a transition from a restrained eating behaviour to a non-restrained eating behaviour. Furthermore, we suggest this transition be leveraged as an opportunity to teach people lifelong eating behaviour to promote healthy weight status by incorporating education and cognitive reappraisal. Our aim was to use a transdisciplinary approach to highlight critical aspects of the emerging closed-loop technologies relating to eating behaviour and weight effects and to promote discussion of strategies to optimize long-term health in Type 1 diabetes via two key outcomes: glycaemic control and weight management.

    View details for DOI 10.1111/dme.13407

    View details for PubMedID 28626906

    View details for PubMedCentralID PMC5647213

  • Closed-Loop Control During Intense Prolonged Outdoor Exercise in Adolescents With Type 1 Diabetes: The Artificial Pancreas Ski Study. Diabetes care Breton, M. D., Cherñavvsky, D. R., Forlenza, G. P., DeBoer, M. D., Robic, J., Wadwa, R. P., Messer, L. H., Kovatchev, B. P., Maahs, D. M. 2017; 40 (12): 1644–50

    Abstract

    Intense exercise is a major challenge to the management of type 1 diabetes (T1D). Closed-loop control (CLC) systems (artificial pancreas) improve glycemic control during limited intensity and short duration of physical activity (PA). However, CLC has not been tested during extended vigorous outdoor exercise common among adolescents.Skiing presents unique metabolic challenges: intense prolonged PA, cold, altitude, and stress/fear/excitement. In a randomized controlled trial, 32 adolescents with T1D (ages 10-16 years) participated in a 5-day ski camp (∼5 h skiing/day) at two sites: Wintergreen, VA, and Breckenridge, CO. Participants were randomized to the University of Virginia CLC system or remotely monitored sensor-augmented pump (RM-SAP). The CLC and RM-SAP groups were coarsely paired by age and hemoglobin A1c(HbA1c). All subjects were remotely monitored 24 h per day by the study physicians and clinical team.Compared with physician-monitored open loop, percent time in range (70-180 mg/dL) improved using CLC: 71.3 vs. 64.7% (+6.6% [95% CI 1-12];P= 0.005), with maximum effect late at night. Hypoglycemia exposure and carbohydrate treatments were improved overall (P= 0.001 andP= 0.007) and during the daytime with strong ski level effects (P= 0.0001 andP= 0.006); ski/snowboard proficiency was balanced between groups but with a very strong site effect: naive in Virginia and experienced in Colorado. There was no adverse event associated with CLC; the participants' feedback was overwhelmingly positive.CLC in adolescents with T1D improved glycemic control and reduced exposure to hypoglycemia during prolonged intensive winter sport activities, despite the added challenges of cold and altitude.

    View details for DOI 10.2337/dc17-0883

    View details for PubMedID 28855239

    View details for PubMedCentralID PMC5711335

  • International Consensus on Use of Continuous Glucose Monitoring. Diabetes care Danne, T., Nimri, R., Battelino, T., Bergenstal, R. M., Close, K. L., DeVries, J. H., Garg, S., Heinemann, L., Hirsch, I., Amiel, S. A., Beck, R., Bosi, E., Buckingham, B., Cobelli, C., Dassau, E., Doyle, F. J., Heller, S., Hovorka, R., Jia, W., Jones, T., Kordonouri, O., Kovatchev, B., Kowalski, A., Laffel, L., Maahs, D., Murphy, H. R., Nørgaard, K., Parkin, C. G., Renard, E., Saboo, B., Scharf, M., Tamborlane, W. V., Weinzimer, S. A., Phillip, M. 2017; 40 (12): 1631–40

    Abstract

    Measurement of glycated hemoglobin (HbA1c) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA1ctesting and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA1cmeasurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes.

    View details for DOI 10.2337/dc17-1600

    View details for PubMedID 29162583

  • Reported gastroparesis in adults with type 1 diabetes (T1D) from the T1D Exchange clinic registry. Journal of diabetes and its complications Aleppo, G., Calhoun, P., Foster, N. C., Maahs, D. M., Shah, V. N., Miller, K. M. 2017; 31 (12): 1669–73

    Abstract

    To better understand the prevalence and impact of gastroparesis in the T1D Exchange clinic registry database.The analysis included 7107 adult participants with T1D across 45 sites (median age 46years. and median duration 24years). Linear and logistic regression models were used to assess the association of gastroparesis vs. no gastroparesis (obtained from medical record) with demographic characteristics, glycemic control and diabetes complications.Among 7107 registry participants, 340 (4.8%) had a clinical diagnosis of gastroparesis. Females were more likely to have gastroparesis compared with males (5.8% vs. 3.5%, P<0.001). Participants with gastroparesis compared with those without gastroparesis were older (median age 49.4 vs. 45.3years, P<0.001), had a longer duration of T1D (median duration 32 vs. 23years, P<0.001), higher mean HbA1c (8.1% vs. 7.7% [65 vs. 61mmol/mol], P<0.001), more frequent severe hypoglycemia (25% vs. 11% with ≥1 event in the past 12months, P<0.001), lower socio-economic status, less likely to be using CGM and insulin pump and greater prevalence of microvascular and neuropathic complications than participants without gastroparesis.Gastroparesis is associated with higher risk of severe hypoglycemia despite higher HbA1c levels than in T1D patients without gastroparesis. The increased presence of multiple long-term complications and overall poor glycemic control in these subjects emphasizes the need to establish diagnostic protocols for earlier diagnosis, achieve tighter glycemic control with more extensive use of insulin pumps and continuous glucose monitoring, and the need for wider availability of medical therapies for treatment of diabetic gastroparesis.

    View details for DOI 10.1016/j.jdiacomp.2017.08.014

    View details for PubMedID 28989086

  • In-Home Closed Loop Control for Artificial Pancreas: Patient and Provider Perspective DIABETES TECHNOLOGY & THERAPEUTICS Ekhlaspour, L., Maahs, D. M. 2017; 19 (1): 4–6

    View details for DOI 10.1089/dia.2016.0432

    View details for Web of Science ID 000392822900002

    View details for PubMedID 28055224

  • Implementation of Depression Screening and Global Health Assessment in Pediatric Subspecialty Clinics. The Journal of adolescent health : official publication of the Society for Adolescent Medicine Iturralde, E., Adams, R. N., Barley, R. C., Bensen, R., Christofferson, M., Hanes, S. J., Maahs, D. M., Milla, C., Naranjo, D., Shah, A. C., Tanenbaum, M. L., Veeravalli, S., Park, K. T., Hood, K. K. 2017

    Abstract

    Adolescents with chronic illness face greater risk of psychosocial difficulties, complicating disease management. Despite increased calls to screen for patient-reported outcomes, clinical implementation has lagged. Using quality improvement methods, this study aimed to investigate the feasibility of standardized screening for depression and assessment of global health and to determine recommended behavioral health follow-up, across three pediatric subspecialty clinics.A total of 109 patients aged 12-22 years (median = 16.6) who were attending outpatient visits for treatment of diabetes (80% type 1), inflammatory bowel disease, or cystic fibrosis completed the 9-item Patient Health Questionnaire (PHQ-9) depression and Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Global Health measures on electronic tablets. Patients screening positive on the PHQ-9 received same-day behavioral health assessment and regular phone check-ins to facilitate necessary follow-up care.Overall, 89% of 122 identified patients completed screening during a 6-month window. Patients completed measures in a timely manner (within 3 minutes) without disruption to clinic flow, and they rated the process as easy, comfortable, and valuable. Depression scores varied across disease type. Patients rated lower global health relative to a previously assessed validation cohort. Depression and global health related significantly to certain medical outcomes. Fifteen percent of patients screened positive on the PHQ-9, of whom 50% confirmed attending behavioral health appointments within 6 months of screening.A standardized depression and global health assessment protocol implemented across pediatric subspecialties was feasible and effective. Universal behavioral health screening for adolescents and young adults living with chronic disease is necessary to meet programmatic needs in pediatric subspecialty clinics.

    View details for DOI 10.1016/j.jadohealth.2017.05.030

    View details for PubMedID 28830798

  • Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs) SENSORS Howsmon, D. P., Cameron, F., Baysal, N., Ly, T. T., Forlenza, G. P., Maahs, D. M., Buckingham, B. A., Hahn, J., Bequette, B. W. 2017; 17 (1)

    Abstract

    Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis-a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios.

    View details for DOI 10.3390/s17010161

    View details for Web of Science ID 000393021000160

    View details for PubMedID 28098839

    View details for PubMedCentralID PMC5298734

  • Ambulatory glucose profile analysis of the juvenile diabetes research foundation continuous glucose monitoring dataset-Applications to the pediatric diabetes population. Pediatric diabetes Forlenza, G. P., Pyle, L. L., Maahs, D. M., Dunn, T. C. 2016

    Abstract

    Increased continuous glucose monitor (CGM) use presents both the benefit and burden of increased data for clinicians to rapidly analyze. The ambulatory glucose profile (AGP) is an evolving a universal software report for CGM data analysis.We utilized the Juvenile Diabetes Research Foundation-CGM dataset to evaluate the AGP across a broad spectrum of patients to show how AGP can be used clinically to assist with CGM-related decision making. We hypothesized that AGP metrics would be different across age and HbA1c strata.AGPs were generated from the JDRF-CGM trial dataset for all periods during which there were ≥10 days of CGM coverage in the 2 weeks adjacent to an HbA1c measurement yielding 1101 AGPs for 393 unique subjects.AGPs were stratified by age group (8-14, 15-24, and ≥25 years) and HbA1c (within or above target for age) and compared for between group differences in AGP metrics via two-factor ANOVA. Glycemic differences between time periods were analyzed via segmented regression analysis.Glucose exposure (average and estimated A1c) and variability (standard deviation and interquartile range) were different between the low and high HbA1c levels. Within a given HbA1c level all age groups were significantly different from each other with older patients having lower averages with less variability than younger patients.AGP analysis of the JDRF-CGM data highlights significant differences in glycemic profiles between pediatric and adult age groups and between well and less well-controlled patient populations.

    View details for DOI 10.1111/pedi.12474

    View details for PubMedID 27878929

  • Severe hypoglycemia rates are not associated with HbA1c: a cross-sectional analysis of 3 contemporary pediatric diabetes registry databases. Pediatric diabetes Haynes, A., Hermann, J. M., Miller, K. M., Hofer, S. E., Jones, T. W., Beck, R. W., Maahs, D. M., Davis, E. A., Holl, R. W. 2016

    Abstract

    To examine the association between glycated hemoglobin (HbA1c) and severe hypoglycemia rates in patients with type 1 diabetes receiving usual care, by analysing data from the US Type 1 Diabetes Exchange (T1DX), German/Austrian Diabetes Patienten Verlaufsdokumenation (DPV), and Western Australian Children Diabetes Database (WACDD) diabetes registries.Data for patients with type 1 diabetes, aged <18 years with a minimum duration of diabetes of 2 years, were extracted from each registry for a 12-month observation period between 2011 and 2012 (7,102 T1DX, 18,887 DPV, and 865 WACDD). Rates of severe hypoglycemia (self-reported loss of consciousness/convulsion) were estimated per 100 patient-years and analyzed by HbA1c, source registry, treatment regimen, and age group.Overall, the severe hypoglycemia rate per 100 patient years was 7.1, 3.3, and 6.7 in T1DX, DPV, and WACDD patients, respectively. Lower HbA1c was not associated with an increased rate of severe hypoglycemia when examined by source registry, treatment regimen, or age group.An inverse relationship between mean HbA1c and risk of severe hypoglycemia was not observed in this study of 3, independent cohorts of children and adolescents with type 1 diabetes. Investigation in other large, longitudinal cohorts is recommended to further characterize the contemporary relationship between glycemic control and risk of severe hypoglycemia rates in pediatric patients with type 1 diabetes.

    View details for DOI 10.1111/pedi.12477

    View details for PubMedID 27878914

  • Characteristics of youth with type 1 diabetes (T1D) with and without a parent with T1D in the T1D exchange clinic registry. Journal of diabetes Fox, L. A., Mubasher, M., Wolfsdorf, J. I., Buckingham, B. A., Peters, A. L., Tamborlane, W. V., Schatz, D. A., Maahs, D. M., Miller, K. M., Beck, R. W. 2016; 8 (6): 834-838

    Abstract

    The aim of the present study was to compare characteristics and diabetes management in children and adolescents with and without at least one parent with type 1 diabetes (T1D).In all, 12 890 participants aged <18 years at enrollment in the T1D Exchange Registry were included in the present study. Statistical comparisons between those with and without parental T1D were conducted using a univariate generalized linear mixed model.Of the study participants, 1056 (8.2%) registrants had at least one parent with T1D. Those with parental T1D were slightly, albeit significantly, younger (6.3 vs 6.9 years; P < 0.001) and less likely to have diabetic ketoacidosis (DKA) at diagnosis (24% vs 41%; P < 0.001) than those without parental T1D. There were no differences between groups in HbA1c, use of continuous glucose monitoring or insulin pump therapy, or the development of severe hypoglycemia or DKA. In addition, there were no differences found when comparing characteristics or diabetes management in those with a mother versus those with a father with T1D.Children and adolescents with parental T1D tend to be diagnosed earlier. Diabetes management, glycemic control, and acute complications are similar in those with and without parental T1D.

    View details for DOI 10.1111/1753-0407.12363

    View details for PubMedID 26663683

  • The Gomez equations and renal hemodynamic function in kidney disease research AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Bjornstad, P., Skrtic, M., Lytvyn, Y., Maahs, D. M., Johnson, R. J., Cherney, D. Z. 2016; 311 (5): F967-F975
  • Efficacy of an Overnight Predictive Low-Glucose Suspend System in Relation to Hypoglycemia Risk Factors in Youth and Adults With Type 1 Diabetes. Journal of diabetes science and technology Calhoun, P. M., Buckingham, B. A., Maahs, D. M., Hramiak, I., Wilson, D. M., Aye, T., Clinton, P., Chase, P., Messer, L., Kollman, C., Beck, R. W., Lum, J. 2016; 10 (6): 1216-1221

    Abstract

    We developed a system to suspend insulin pump delivery overnight when the glucose trend predicts hypoglycemia. This predictive low-glucose suspend (PLGS) system substantially reduces nocturnal hypoglycemia without an increase in morning ketosis. Evaluation of hypoglycemia risk factors that could potentially influence the efficacy of the system remains critical for understanding possible problems with the system and identifying patients that may have the greatest benefit when using the system.The at-home randomized trial consisted of 127 study participants with hemoglobin A1c (A1C) of ≤8.5% (mmol/mol) for patients aged 4-14 years and ≤8.0% for patient aged 15-45 years. Factors assessed included age, gender, A1C, diabetes duration, daily percentage basal insulin, total daily dose of insulin (units/kg-day), bedtime BG, bedtime snack, insulin on board, continuous glucose monitor (CGM) rate of change (ROC), day of the week, time system activated, daytime exercise intensity, and daytime CGM-measured hypoglycemia.The PLGS system was effective in preventing hypoglycemia for each factor subgroup. There was no evidence that the PLGS system was more or less effective in preventing hypoglycemia in any one subgroup compared with the other subgroups based on that factor. In addition, the effect of the system on overnight hyperglycemia did not differ in subgroups.The PLGS system tested in this study effectively reduced hypoglycemia without a meaningful increase in hyperglycemia across a variety of factors.

    View details for PubMedID 27207890

    View details for PubMedCentralID PMC5094319

  • Early Detection of Infusion Set Failure During Insulin Pump Therapy in Type 1 Diabetes. Journal of diabetes science and technology Cescon, M., DeSalvo, D. J., Ly, T. T., Maahs, D. M., Messer, L. H., Buckingham, B. A., Doyle, F. J., Dassau, E. 2016; 10 (6): 1268-1276

    Abstract

    Insulin infusion set failure resulting in prolonged hyperglycemia or diabetic ketoacidosis can occur with pump therapy in type 1 diabetes. Set failures are frequently characterized by variable and unpredictable patterns of increasing glucose values despite increased insulin infusion. Early detection may minimize the risk of prolonged hyperglycemia, an important consideration for automated insulin delivery and closed-loop applications.A novel algorithm designed to alert the patient to the onset of infusion set failure was developed based upon continuous glucose sensor values and insulin delivered from an insulin pump. The method was calibrated on 12 weeks of infusion set wear without failures recorded by 4 patients in ambulatory conditions and prospectively validated on 18 weeks of infusion set wear with and without failures belonging to 9 other subjects in ambulatory conditions.The algorithm, evaluated retrospectively, identified a failure 2.52 ± 1.91 days ahead of the actual event as recorded by the clinical team, corresponding to 50% sensitivity, 66% specificity and 55% accuracy. If set failure alarms had been activated in real time, the average time >180 mg/dl would be reduced from 82.7 ± 40.9 hours/week/subject (without alarm) to 58.8 ± 31.1 hours/week/subject (with alarm), corresponding to a potential 29% reduction in time spent >180mg/dl.The proposed method for early detection of infusion set failure based on glucose sensor and insulin data demonstrated favorable results on retrospective data and may be implemented as an additional safeguard in a future fully automated closed-loop system.

    View details for PubMedID 27621142

    View details for PubMedCentralID PMC5094340

  • A survey of youth with new onset type 1 diabetes: Opportunities to reduce diabetic ketoacidosis. Pediatric diabetes Baldelli, L., Flitter, B., Pyle, L., Maahs, D. M., Klingensmith, G., Slover, R., Alonso, G. T. 2016

    Abstract

    Pediatric patients in Colorado with new onset type 1 diabetes (T1D) presenting with diabetic ketoacidosis (DKA) increased from 29.9% to 46.2% from 1998 to 2012. The purpose of this study was to compare differences between patients with newly diagnosed T1D who presented in DKA with those who did not across three domains: sociodemographic factors, access to medical care, and medical provider factors, aiming to identify potential targets for intervention.Sixty-one patients <17 years of age with T1D duration <6 months completed the questionnaire. Groups were compared using Fisher's exact test or the Kruskal-Wallis test.Parents of 28% of patients researched their child's symptoms on the Internet prior to diagnosis. At the first healthcare visit for symptoms of T1D, 23% were not diagnosed. There were no significant differences between groups (DKA vs non-DKA) in demographics, first healthcare setting for T1D symptoms, provider type at first visit or at diagnosis, insurance status, or specific barriers to care. DKA patients had a longer interval between previous well visit to diagnosis (median 172 vs 263 days, P = 0.01). Non-DKA patients were more likely to have blood glucose measured at P = 0.02, and had fewer symptoms prior to (P = 0.01) the first visit for diabetes symptoms. Parents of non-DKA patients were more likely to be familiar with symptoms of diabetes (P < 0.001) and to suspect diabetes (P = 0.01).Targets for campaigns to prevent DKA include increasing provider glucose and ketone testing, increasing public knowledge about diabetes, and understanding how socio-demographic factors may delay T1D diagnosis.

    View details for DOI 10.1111/pedi.12455

    View details for PubMedID 27726268

  • Type 1 diabetes in older adults: Comparing treatments and chronic complications in the United States T1D Exchange and the German/Austrian DPV registries. Diabetes research and clinical practice Weinstock, R. S., Schütz-Fuhrmann, I., Connor, C. G., Hermann, J. M., Maahs, D. M., Schütt, M., Agarwal, S., Hofer, S. E., Beck, R. W., Holl, R. W. 2016; 122: 28-37

    Abstract

    Compare characteristics, therapies and clinical outcomes in older adults with type 1 diabetes in the United States T1D Exchange (T1DX) and German/Austrian Diabetes Patienten Verlaufsdokumentation (DPV) registries.Cross-sectional study of adults ≥60years old with type 1 diabetes seen in 2011-2012 in the T1DX (n=1283) and DPV (n=2014) registries. Wilcoxon rank-sum test was used for continuous variables and chi-square test for categorical variables. Adjusted analyses used generalized linear models.Individuals in both registries were similar in body mass index (mean 27kg/m(2)), percent with obesity (25%) and gender (48% male). In T1DX there was longer diabetes duration (32.3 vs. 28.8years), greater use of antihypertensive medications (including ACE-I and ARBs; 85% vs. 62%), statins (68% vs. 40%), aspirin (77% vs. 21%), insulin pumps (58% vs. 18%), and less smoking (7% vs. 10%); lower adjusted mean LDL-cholesterol (84 vs. 109mg/dL), and lower adjusted mean systolic and diastolic blood pressures (128 vs. 136 and 68 vs. 74mmHg); fewer myocardial infarctions (6% vs. 9% [99% CI of difference, 1% to 5%]), strokes (2% vs. 8% [3% to 7%]), microvascular complications including microalbuminuria (17% vs. 44% [22% to 32%]) but increased depression (16.1% vs. 8.7%). Adjusted mean HbA1c levels were similar (7.5%, 58mmol/mol).Differences between the registries included greater use of antihypertensives, statins and insulin pumps, and fewer chronic complications in the T1DX. Further research is needed to better understand the role of intensive therapy in improving outcomes in older adults with type 1 diabetes.

    View details for DOI 10.1016/j.diabres.2016.09.024

    View details for PubMedID 27764721

  • Insulin pump therapy in children with type 1 diabetes: analysis of data from the SWEET registry PEDIATRIC DIABETES Szypowska, A., Schwandt, A., Svensson, J., Shalitin, S., Cardona-Hernandez, R., Forsander, G., Sundberg, F., De Beaufort, C., Maahs, D., Maffeis, C., O'Riordan, S. M., Krisane, I. D., Scharf, M., Castro, S., Konstantinova, M., Obermannova, B., Casteels, K., Goksen, D., Galhardo, J., Kanaka-Gantenbein, C., Rami-Merhar, B., Madacsy, L. 2016; 17: 38-45

    Abstract

    Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control.To examine the frequency of pump usage in T1D children treated in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI.This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized diabetes patient registry. Datasets were aggregated over the most recent year of treatment for each patient. Data were collected until March 2016. To assess the organization of pump therapy a survey was carried out.Overall, 44.4% of T1D children were treated with CSII. The proportion of patients with pump usage varied between centers and decreased with increasing age compared with children treated with MDI. In a logistic regression analysis adjusting for age, gender and diabetes duration, the use of pump was associated with both: center size [odd ratio 1.51 (1.47-1.55), P < .0001) and the diabetes-related expenditure per capita [odd ratio 1.55 (1.49-1.61), P < .0001]. Linear regression analysis, adjusted for age, gender, and diabetes duration showed that both HbA1c and daily insulin dose (U/kg/d) remained decreased in children treated with CSII compared to MDI (P < .0001).Insulin pump therapy is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age.

    View details for DOI 10.1111/pedi.12416

    View details for Web of Science ID 000389153800006

    View details for PubMedID 27417128

  • The Gomez' equations and renal hemodynamic function in kidney disease research. American journal of physiology. Renal physiology Bjornstad, P., Škrtic, M., Lytvyn, Y., Maahs, D. M., Johnson, R. J., Cherney, D. Z. 2016: ajprenal 00415 2016-?

    Abstract

    Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease. A major challenge in preventing DKD is the difficulty in identifying high-risk patients at an early, pre-clinical stage. Albuminuria and eGFR as measures of renal function in DKD research and clinical practice are limited by regression of one-third of patients with microalbuminuria to normoalbuminuria and eGFR is biased and imprecise in the normal-elevated range. Moreover, existing methods that are used to assess renal function do not give detailed insight into the location of the renal hemodynamic effects of pharmacological agents at the segmental level. To gain additional information about the intrarenal circulation in-vivo in humans, mathematical equations were developed by Gomez et al in the 1950s. These equations used measurements of GFR, renal blood flow (RBF), effective renal plasma flow (ERPF), renal vascular resistance (RVR), hematocrit and serum protein to calculate afferent and efferent arteriolar resistances, glomerular hydrostatic pressure and filtration pressure. Although indirect and based on physiological assumptions, these techniques have the potential to improve researchers' ability to identify early pre-clinical changes in renal hemodynamic function in patients with a variety of conditions including DKD, thereby offering tremendous potential in mechanistic human research studies. In this review, we focus on the application of Gomez' equations and summarize the potential and limitations of this technique in DKD research. We also summarize illustrative data derived from Gomez' equations in patients with type 1 (T1D) and type 2 diabetes (T2D) and hypertension.

    View details for DOI 10.1152/ajprenal.00415.2016

    View details for PubMedID 27605583

  • Elevated copeptin is associated with atherosclerosis and diabetic kidney disease in adults with type 1 diabetes. Journal of diabetes and its complications Bjornstad, P., Maahs, D. M., Jensen, T., Lanaspa, M. A., Johnson, R. J., Rewers, M., Snell-Bergeon, J. K. 2016; 30 (6): 1093-1096

    Abstract

    Vasopressin exerts important cardio-renal effects, but remains problematic to measure. Copeptin is a more stable peptide derived from the same precursor molecule. We examined the associations between copeptin, coronary artery calcium (CAC), albuminuria and impaired glomerular filtration rate (GFR) in adults with type 1 diabetes (T1D).Participants with (n=209) and without T1D (n=244) in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study were assessed for serum copeptin, CAC measured using 128-slice spiral CT, urinary albumin-to-creatinine ratio (UACR) and eGFR calculated by CKD-EPI creatinine. Impaired GFR was defined as eGFR <60mL/min/1.73m(2), albuminuria as UACR ≥30mg/g, high and very high CAC score as ≥100 and ≥300AU, and elevated copeptin as >13pmol/L (>97.5th percentile for healthy adults). Unadjusted and adjusted (age, sex, HbA1c, SBP and LDL-C) logistic models were applied to examine the relationships.Participants with T1D had greater ultrasensitive copeptin concentrations than non-diabetics (3.5 [95% CI 2.3-3.8] vs. 2.8 [2.7-3.1], p=0.003). In participants with T1D, elevated copeptin was associated with greater odds of impaired eGFR (OR: 18.52, 95% CI 4.03-85.02), albuminuria (10.55, 2.24-49.62), high CAC (6.61, 1.39-31.31) and very high CAC (6.24, 1.51-25.90) in multivariable models. Similar linear relationships were obtained with ultrasensitive copeptin, eGFR, UACR, CAC volume and CAC score in adjusted models.In this cross-sectional analysis, copeptin was strongly associated with diabetic kidney disease and coronary atherosclerosis in adults with T1D. Further research is needed to determine whether these relationships hold true longitudinally in people with T1D.

    View details for DOI 10.1016/j.jdiacomp.2016.04.012

    View details for PubMedID 27141815

    View details for PubMedCentralID PMC4949105

  • Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry PEDIATRIC DIABETES Clements, M. A., Foster, N. C., Maahs, D. M., Schatz, D. A., Olson, B. A., Tsalikian, E., Lee, J. M., Burt-Solorzano, C. M., Tamborlane, W. V., Chen, V., Miller, K. M., Beck, R. W. 2016; 17 (5): 327-336

    Abstract

    Hemoglobin A1c (HbA1c) levels among individuals with type 1 diabetes (T1D) influence the longitudinal risk for diabetes-related complications. Few studies have examined HbA1c trends across time in children, adolescents, and young adults with T1D. This study examines changes in glycemic control across the specific transition periods of pre-adolescence-to-adolescence and adolescence-to-young adulthood, and the demographic and clinical factors associated with these changes.Available HbA1c lab results for up to 10 yr were collected from medical records at 67 T1D Exchange clinics. Two retrospective cohorts were evaluated: the pre-adolescent-to-adolescent cohort consisting of 85 016 HbA1c measurements from 6574 participants collected when the participants were 8-18 yr old and the adolescent-to-young adult cohort, 2200 participants who were 16-26 yr old at the time of 17 279 HbA1c measurements.HbA1c in the 8-18 cohort increased over time after age 10 yr until ages 16-17; followed by a plateau. HbA1c levels in the 16-26 cohort remained steady from 16-18, and then gradually declined. For both cohorts, race/ethnicity, income, health insurance, and pump use were all significant in explaining individual variations in age-centered HbA1c (p < 0.001). For the 8-18 cohort, insulin pump use, age of onset, and health insurance were significant in predicting individual HbA1c trajectory.Glycemic control among patients 8-18 yr old worsens over time, through age 16. Elevated HbA1c levels observed in 18 yr-olds begin a steady improvement into early adulthood. Focused interventions to prevent deterioration in glucose control in pre-adolescence, adolescence, and early adulthood are needed.

    View details for DOI 10.1111/pedi.12295

    View details for Web of Science ID 000379832500003

    View details for PubMedID 26153338

  • Ketone production in children with type 1 diabetes, ages 4-14 years, with and without nocturnal insulin pump suspension. Pediatric diabetes Wadwa, R. P., Chase, H. P., Raghinaru, D., Buckingham, B. A., Hramiak, I., Maahs, D. M., Messer, L., Ly, T., Aye, T., Clinton, P., Kollman, C., Beck, R. W., Lum, J. 2016

    Abstract

    To compare the frequency of elevated morning blood ketone levels according to age in 4-14 year olds with type 1 diabetes following overnight use of an automated low glucose insulin suspension system, or following control nights when the system was not used.For 28 children ages 4-9 years and 54 youth ages 10-14 years, elevation of morning blood ketone levels was assessed using the Precision Xtra Ketone meter following 1155 and 2345 nights, respectively. Repeated measures logistic regression models were used to compare age groups for blood ketone level elevation following control nights (system not activated) and following intervention nights with and without insulin suspension.Elevated morning blood ketones (≥0.6 mmol/L) were present following 10% of 580 control nights in the 4-9 year olds compared with 2% of 1162 control nights in 10-14 year olds (P < 0.001). Likewise, the frequency was greater following intervention nights in the younger age group (13% of 575 nights vs 2% of 1183 nights, P < 0.001). A longer duration of pump suspension resulted in a higher percentage of mornings with elevated blood ketones in the younger age group (P = 0.002), but not in the older age group (P = 0.63). The presence of elevated morning ketone levels did not progress to ketoacidosis in any subject.Elevated morning blood ketones are more common in younger children with type 1 diabetes with or without nocturnal insulin suspension. Care providers need to be aware of the differences in ketogenesis in younger age children relative to various clinical situations.

    View details for DOI 10.1111/pedi.12410

    View details for PubMedID 27402452

  • Duration of Infusion Set Survival in Lipohypertrophy Versus Nonlipohypertrophied Tissue in Patients with Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Karlin, A. W., Ly, T. T., Pyle, L., Forlenza, G. P., Messer, L., Wadwa, R. P., DeSalvo, D. J., Payne, S. L., Hanes, S., Clinton, P., Maahs, D. M., Buckingham, B. 2016; 18 (7): 429-435

    Abstract

    Improved insulin infusion set survival and faster insulin action are important issues for pump users and for the development of an artificial pancreas. The current recommendation is to change infusion sets every 3 days. Our objectives were to determine the effect of lipohypertrophy (LH) on infusion set survival and continuous glucose monitoring glucose levels.In this multicenter crossover trial, we recruited 20 subjects (age 28.1 ± 9.0 years) with type 1 diabetes (duration 17.5 ± 8.8 years) and an area of lipohypertrophied tissue >3 cm. Subjects alternated weekly wearing a Teflon infusion set in an area of either LH or non-LH for 4 weeks. Sets were changed after (a) failure or (b) surviving 7 days of use.The least-squares mean duration of infusion set survival for sets that lasted <7 days in lipohypertrophied tissue was 4.31 days compared with 4.12 days in nonlipohypertrophied tissue (P = 0.71). The average duration of set survival for individual subjects ranged from 2.2 to 7.0 days. Infusion sets in lipohypertrophied tissue failed due to hyperglycemia in 35% of subjects compared with 23% in nonlipohypertrophied tissue (P = 0.22). Both lipohypertrophied and nonlipohypertrophied tissues displayed a general increase in mean daily glucose after the third day of infusion set wear, but daily mean glucose did not differ by tissue type (P > 0.38 on each day).LH did not significantly affect infusion set survival or mean glucose. Achieving optimal infusion set performance requires research into factors affecting set survival. Additionally, the recommendation for duration of set change may need to be individualized.

    View details for DOI 10.1089/dia.2015.0432

    View details for Web of Science ID 000379497600006

    View details for PubMedID 27227290

    View details for PubMedCentralID PMC4931738

  • Outcome Measures for Artificial Pancreas Clinical Trials: A Consensus Report. Diabetes care Maahs, D. M., Buckingham, B. A., Castle, J. R., Cinar, A., Damiano, E. R., Dassau, E., DeVries, J. H., Doyle, F. J., Griffen, S. C., Haidar, A., Heinemann, L., Hovorka, R., Jones, T. W., Kollman, C., Kovatchev, B., Levy, B. L., Nimri, R., O'Neal, D. N., Philip, M., Renard, E., Russell, S. J., Weinzimer, S. A., Zisser, H., Lum, J. W. 2016; 39 (7): 1175-1179

    Abstract

    Research on and commercial development of the artificial pancreas (AP) continue to progress rapidly, and the AP promises to become a part of clinical care. In this report, members of the JDRF Artificial Pancreas Project Consortium in collaboration with the wider AP community 1) advocate for the use of continuous glucose monitoring glucose metrics as outcome measures in AP trials, in addition to HbA1c, and 2) identify a short set of basic, easily interpreted outcome measures to be reported in AP studies whenever feasible. Consensus on a broader range of measures remains challenging; therefore, reporting of additional metrics is encouraged as appropriate for individual AP studies or study groups. Greater consistency in reporting of basic outcome measures may facilitate the interpretation of study results by investigators, regulatory bodies, health care providers, payers, and patients themselves, thereby accelerating the widespread adoption of AP technology to improve the lives of people with type 1 diabetes.

    View details for DOI 10.2337/dc15-2716

    View details for PubMedID 27330126

    View details for PubMedCentralID PMC4915553

  • Reduced brachial artery distensibility in patients with type 1 diabetes JOURNAL OF DIABETES AND ITS COMPLICATIONS Ljunggren, P., Maahs, D. M., Johansson, P., Ludvigsson, J., Pyle, L., Sippl, R., Wadwa, R. P., Snell-Bergeon, J. 2016; 30 (5): 893-897

    Abstract

    In patients with type 1 diabetes mellitus (T1D), cardiovascular disease (CVD) events are more common and occur earlier in life than in non-diabetics. Reduced brachial artery distensibility (BrachD) is an independent risk factor for development of CVD. Our aim was to determine if adults with T1D have lower BrachD compared to adults without diabetes and also to determine how age and gender affect the relationship of BrachD with T1D status.BrachD was measured using the Dynapulse instrument in 829 participants (352 with T1D, 477 non-diabetics). An ANCOVA model was used to test the association of BrachD with age, sex, and T1D, and the significance of an age*sex*T1D interaction.Mean BrachD was lower in T1D patients vs. controls (6.43±1.46 vs. 7.16±1.48 % change per mmHg, p<0.0001). In a model adjusted for age, T1D, and sex, the interaction of age*T1D*sex was significant (p=0.0045). Younger women both with and without T1D had higher BrachD than men with and without T1D, but older women with and without T1D had lower BrachD compared to older men with and without T1D. Women with T1D had a steeper decline in BrachD with age than nondiabetic women.BrachD is lower in T1D patients than in non-diabetics, indicating increased vascular stiffness. Younger females have higher BrachD than males, but the decline with age in BrachD is steeper for women, particularly among those with T1D. BrachD may be an inexpensive, non-invasive method to ascertain increased CVD risk in this population.

    View details for DOI 10.1016/j.jdiacomp.2016.03.004

    View details for Web of Science ID 000378759700024

    View details for PubMedID 27056753

    View details for PubMedCentralID PMC4912899

  • Adiponectin is associated with early diabetic kidney disease in adults with type 1 diabetes: A Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. Journal of diabetes and its complications Bjornstad, P., Pyle, L., Kinney, G. L., Rewers, M., Johnson, R. J., Maahs, D. M., Snell-Bergeon, J. K. 2016

    Abstract

    The associations between elevated adiponectin and end-stage renal disease are well recognized and thought to be at least partially explained by reduced renal clearance. Conversely, the relationship between adiponectin and early diabetic kidney disease (DKD) with preserved glomerular filtration rate (GFR), including rapid GFR decline and incident chronic kidney disease (CKD) is unclear. We hypothesized that elevated adiponectin would be associated with early DKD in adults with type 1 diabetes.Adults with type 1 diabetes (n=646 at baseline, n=525 at 6years) had adiponectin and renal function by estimated GFR (eGFR) by CKD-EPI creatinine and albumin-excretion rate (AER) evaluated at baseline and 6years. Linear and logistic models evaluated the associations of baseline adiponectin with AER, macroalbuminuria (AER ≥200μg/min), eGFR, CKD (<60mL/min/1.73m(2)) and rapid GFR decline (>3mL/min/1.73m(2)/year). Models adjusted for age, sex, duration, HbA1c, SBP, LDL-C and current smoking.Compared to non-diabetics, adults with type 1 diabetes had significantly higher adiponectin, and the difference remained significant after adjusting for AER and/or eGFR (p<0.0001). Adiponectin at baseline was positively associated with rapid GFR decline (OR: 1.24, 95% CI 1.00-1.53), incident CKD (OR: 1.75, 1.14-2.70), and persistent macroalbuminuria and CKD (OR: 1.61, 1.10-2.36) over 6years in adjusted models. The associations also remained significant after further adjustments for CRP, estimated insulin sensitivity and ACEi/ARB therapy.Adults with type 1 diabetes have higher adiponectin than their non-diabetic peers, and elevated adiponectin at baseline is independently associated with greater odds of developing early DKD over 6years.

    View details for DOI 10.1016/j.jdiacomp.2016.06.012

    View details for PubMedID 27368123

    View details for PubMedCentralID PMC5156602

  • The dose-response effect of insulin sensitivity on albuminuria in children according to diabetes type PEDIATRIC NEPHROLOGY Mottl, A. K., Divers, J., Dabelea, D., Maahs, D. M., Dolan, L., Pettitt, D., Marcovina, S., Imperatore, G., Pihoker, C., Mauer, M., Mayer-Davis, E. J. 2016; 31 (6): 933-940

    Abstract

    Insulin resistance is associated with microalbuminuria among youth with diabetes mellitus. We sought to determine the dose-response effect of insulin sensitivity (IS) on the magnitude of albuminuria and whether there is a threshold below which urine albumin excretion increases.These analyses included participants from the SEARCH for Diabetes in Youth Study with incident diabetes who completed a baseline study visit (n = 2988). We estimated IS using a validated equation incorporating waist circumference, HbA1C, and fasting serum triglycerides. Multivariate regression analyses were performed to assess the effect of IS on urine albumin creatinine ratio (UACR), stratified by diabetes type. The IS threshold was then determined using segmented regressions within each diabetes type and incorporated into the multivariate model.There was an association between IS and UACR in type 2 diabetes only (beta = -0.39; p < 0.001). There was strong statistical evidence for a threshold effect of IS score on UACR in the group of youth with type 2 (beta = 0.40; p < 0.001) but not type 1 diabetes (p = 0.3).In cross-sectional analyses, there is a negative association between IS and UACR in youth with type 2 but not type 1 diabetes, and this association likely includes a threshold effect of IS on UACR.

    View details for DOI 10.1007/s00467-015-3276-2

    View details for Web of Science ID 000374579700007

    View details for PubMedID 26754041

    View details for PubMedCentralID PMC4841707

  • Lipoprotein subfraction cholesterol distribution is more atherogenic in insulin resistant adolescents with type 1 diabetes PEDIATRIC DIABETES Cree-Green, M., Maahs, D. M., Ferland, A., Hokanson, J. E., Wang, H., Pyle, L., Kinney, G. L., King, M., Eckel, R. H., Nadeau, K. J. 2016; 17 (4): 257-265

    Abstract

    Adolescents with type 1 diabetes (T1D) often have a less atherogenic-appearing fasting lipid profile than controls, despite increased rates of cardiovascular disease (CVD) as adults. We previously reported an atherogenic lipoprotein subfraction cholesterol distribution associated with insulin resistance (IR) in T1D adults. We sought to determine if T1D youth have more atherogenic profile than controls via a cross-sectional study.Following 3 days of controlled diet and restricted exercise, fasting plasma samples were drawn from 28 T1D youth [50% female, age 15.3 ± 2 yr, body mass index (BMI) 48%ile; diabetes duration 73 ± 52 months, hemoglobin A1c (HbA1c) 8.3 ± 1.4%] and 17 non-diabetic controls (47% female, age: 15.0 ± 2 yr, BMI 49%ile) prior to a hyperinsulinemic euglycemic clamp. Lipoproteins were fractionated by fast protein liquid chromatography (FPLC) and lipoprotein cholesterol distribution determined. Outcome measures were IR assessed by glucose infusion rate (GIR) and FPLC lipoprotein subfraction cholesterol distribution.T1D youth were more IR (GIR 9.1 ± 3.6 vs. 14.7 ± 3.9 mg/kg/min, p < 0.0001) and had more cholesterol distributed as small dense low density lipoprotein-cholesterol (LDL-C) and less as large buoyant high density lipoprotein-cholesterol (HDL-C) than controls (p < 0.05), despite no differences in the fasting lipid panel. T1D girls lacked the typical female less-atherogenic profile, whereas control girls tended to have a shift toward less dense LDL-C and HDL-C vs. control boys. Among T1D, IR but not HbA1c was associated with a more atherogenic lipoprotein profile.Normal weight T1D youth, especially females, had more atherogenic LDL-C and HDL-C distributions which correlated with lower insulin sensitivity. IR may contribute to the increased CVD burden in T1D.

    View details for DOI 10.1111/pedi.12277

    View details for Web of Science ID 000379831900004

    View details for PubMedID 26080650

    View details for PubMedCentralID PMC4887262

  • Automated hybrid closed-loop control with a proportional-integral-derivative based system in adolescents and adults with type 1 diabetes: individualizing settings for optimal performance. Pediatric diabetes Ly, T. T., Weinzimer, S. A., Maahs, D. M., Sherr, J. L., Roy, A., Grosman, B., Cantwell, M., Kurtz, N., Carria, L., Messer, L., von Eyben, R., Buckingham, B. A. 2016

    Abstract

    Automated insulin delivery systems, utilizing a control algorithm to dose insulin based upon subcutaneous continuous glucose sensor values and insulin pump therapy, will soon be available for commercial use. The objective of this study was to determine the preliminary safety and efficacy of initialization parameters with the Medtronic hybrid closed-loop controller by comparing percentage of time in range, 70-180 mg/dL (3.9-10 mmol/L), mean glucose values, as well as percentage of time above and below target range between sensor-augmented pump therapy and hybrid closed-loop, in adults and adolescents with type 1 diabetes.We studied an initial cohort of 9 adults followed by a second cohort of 15 adolescents, using the Medtronic hybrid closed-loop system with the proportional-integral-derivative with insulin feed-back (PID-IFB) algorithm. Hybrid closed-loop was tested in supervised hotel-based studies over 4-5 days.The overall mean percentage of time in range (70-180 mg/dL, 3.9-10 mmol/L) during hybrid closed-loop was 71.8% in the adult cohort and 69.8% in the adolescent cohort. The overall percentage of time spent under 70 mg/dL (3.9 mmol/L) was 2.0% in the adult cohort and 2.5% in the adolescent cohort. Mean glucose values were 152 mg/dL (8.4 mmol/L) in the adult cohort and 153 mg/dL (8.5 mmol/L) in the adolescent cohort.Closed-loop control using the Medtronic hybrid closed-loop system enables adaptive, real-time basal rate modulation. Initializing hybrid closed-loop in clinical practice will involve individualizing initiation parameters to optimize overall glucose control.

    View details for DOI 10.1111/pedi.12399

    View details for PubMedID 27191182

  • Estimated insulin sensitivity predicts incident micro- and macrovascular complications in adults with type 1 diabetes over 6 years: the coronary artery calcification in type 1 diabetes study JOURNAL OF DIABETES AND ITS COMPLICATIONS Bjornstad, P., Maahs, D. M., Duca, L. M., Pyle, L., Rewers, M., Johnson, R. J., Snell-Bergeon, J. K. 2016; 30 (4): 586-590

    Abstract

    Reduced insulin sensitivity (IS) is well documented in type 1 diabetes (T1D) and may contribute to vascular complications. We examined the association of estimated IS (eIS) with incident macro- and microvascular complications in adults with T1D in the prospective CACTI study.Participants (N=652) were 19-56 years old at baseline and re-examined 6.2±0.6years later. Urinary albumin excretion was measured, and categorized as microalbuminuria or greater. Diabetic retinopathy (DR) was based on self-reported history, proliferative DR (PDR) as history of laser eye therapy and coronary artery calcium (CAC) was measured using electron-beam CT. Progression of CAC was defined as a change in the square root transformed CAC volume score of ≥2.5. IS was estimated (eIS) by an equation derived from clamp studies. Predictors of each complication were examined using stepwise logistic regression and subjects with complications at baseline excluded. Age, T1D duration, sex, HbA1c, SBP, LDL-C, and eIS were considered for inclusion.Greater eIS at baseline predicted lower odds of developing albuminuria (OR: 0.67, 95% CI 0.51-0.88), DR (OR 0.79, 0.64-0.97), PDR (OR: 0.76, 0.57-0.99) and CACp (OR: 0.71, 0.60-0.85) in multivariable models.Greater eIS conferred protection from the development of vascular complications over 6-years in T1D.

    View details for DOI 10.1016/j.jdiacomp.2016.02.011

    View details for Web of Science ID 000374916200004

    View details for PubMedID 26936306

    View details for PubMedCentralID PMC4834265

  • Hyperfiltration and uricosuria in adolescents with type 1 diabetes PEDIATRIC NEPHROLOGY Bjornstad, P., Roncal, C., Milagres, T., Pyle, L., Lanaspa, M. A., Bishop, F. K., Snell-Bergeon, J. K., Johnson, R. J., Wadwa, R. P., Maahs, D. M. 2016; 31 (5): 787-793

    Abstract

    Urine uric acid (UUA) has been implicated in the pathogenesis of diabetic nephropathy via its effect on tubular cells. We hypothesized that the UUA level would be higher in adolescents with type 1 diabetes (T1D) than in those without T1D. We also hypothesized that UUA and fractional uric acid excretion (FeUA) would be higher in adolescents with T1D and hyperfiltration [estimated glomerular filtration rate (eGFR) ≥141 mL/min/1.73 m(2)] than in those without hyperfiltration.The UUA concentration was determined and FeUA calculated in adolescents with (n = 239) and without T1D (n = 75). The eGFR was calculated using the Zappitelli equation based on serum creatinine and cystatin C concentrations.Compared to the non-diabetic adolescents enrolled in the study, those with T1D had a higher eGFR (mean ± standard deviation: 120 ± 22 vs. 112 ± 16 mL/min/1.73 m(2); p = 0.0006), lower urine pH (6.2 ± 0.8 vs. 6.5 ± 1.0; p = 0.01), and higher UUA (37.7 ± 18.6 vs. 32.8 ± 18.1 mg/dL; p  = 0.049) and FeUA (median [interquartile range]: 6.2 [4.3-8.7] vs. 5.2 [3.6-7.0] %; p = 0.02). Among adolescents with T1D, those with hyperfiltration had higher median FeUA (8.6 [5.2-9.9] vs. 6.0 [4.2-8.3] %; p = 0.02) than those without hyperfiltration.The adolescents with T1D enrolled in the study had higher eGFR, higher UUA and more acidic urine than the non-diabetic controls, which may have increased their risk of UUA crystallization. Adolescents with T1D and hyperfiltration had higher FeUA than those without hyperfiltration. These hypothesis-generating observations may suggest a potential pathophysiologic association between uricosuria and hyperfiltration.

    View details for DOI 10.1007/s00467-015-3299-8

    View details for Web of Science ID 000373305100012

    View details for PubMedID 26701836

    View details for PubMedCentralID PMC4808359

  • In-home nighttime predictive low glucose suspend experience in children and adults with type 1 diabetes. Pediatric diabetes Messer, L. H., Calhoun, P., Buckingham, B., Wilson, D. M., Hramiak, I., Ly, T. T., Driscoll, M., Clinton, P., Maahs, D. M. 2016: -?

    Abstract

    Overnight predictive low glucose suspend (PLGS) reduces hypoglycemia across all ages; however, there are no reports on behavior or experience differences across age groups, especially in pediatrics. As run-in for a subsequent randomized clinical trial (RCT), 127 subjects (50% male) ages 4-45 yr utilized the experimental PLGS system nightly for 5-10 nights (PLGS active phase). We analyzed the number of blood glucose (BG) checks and boluses given per age group. During the subsequent 42 night RCT phase, we analyzed sensor use, skin reactions, errors, and reasons why the experimental system was not used. In 821 nights of active PLGS, subjects ages 4-6 yr (and their parents) tested BG levels 75% of nights compared with 65% of nights (7-10 yr), 53% of nights (11-14 yr), 33% of nights (15-25 yr), and 28% of nights (26-45 yr), respectively (p < 0.001). Likewise, youngest subjects (and parents) administered insulin boluses 56% of nights during active PLGS use compared with 48%, 33%, 20%, and 25%, respectively (p < 0.001). This was unrelated to study requirements. During the RCT phase, subjects 4-6 yr experienced more frequent and severe skin reactions (p = 0.02), while adult subjects (26-45 yr) wore individual sensors a median of 26 h longer than the youngest subjects (p < 0.001). Technical problems with the sensor (errors, miscalibrations, etc.), traveling, and BG levels >270 at bedtime (study requirement) were primary contributors to non-system use. Understanding the different use patterns and challenges in pediatrics and adolescence is needed to direct patient education to optimize use of PLGS and future artificial pancreas systems.

    View details for DOI 10.1111/pedi.12395

    View details for PubMedID 27125223

    View details for PubMedCentralID PMC5086306

  • Measuring glomerular filtration rate by iohexol clearance on filter paper is feasible in adolescents with type 1 diabetes in the ambulatory setting ACTA DIABETOLOGICA Bjornstad, P., Anderson, P. L., Maahs, D. M. 2016; 53 (2): 331-333

    View details for DOI 10.1007/s00592-015-0764-6

    View details for Web of Science ID 000373951300018

    View details for PubMedID 25959420

    View details for PubMedCentralID PMC4643415

  • Prevalence of cardiovascular risk factors in youth with type 1 diabetes and elevated body mass index. Acta diabetologica Redondo, M. J., Foster, N. C., Libman, I. M., Mehta, S. N., Hathway, J. M., Bethin, K. E., Nathan, B. M., Ecker, M. A., Shah, A. C., DuBose, S. N., Tamborlane, W. V., Hoffman, R. P., Wong, J. C., Maahs, D. M., Beck, R. W., Dimeglio, L. A. 2016; 53 (2): 271-277

    Abstract

    The prevalence of cardiovascular risk factors in children with type 1 diabetes and elevated BMI in the USA is poorly defined. We aimed to test the hypothesis that children with type 1 diabetes who are overweight or obese have increased frequencies of hypertension, dyslipidemia, and micro-/macroalbuminuria compared to their healthy weight peers.We studied 11,348 children 2 to <18 years of age enrolled in T1D Exchange between September 2010 and August 2012 with type 1 diabetes for ≥1 year and BMI ≥ 5th age-/sex-adjusted percentile (mean age 12 years, 49 % female, 78 % non-Hispanic White). Overweight and obesity were defined based on Centers for Disease Control and Prevention criteria. Diagnoses of hypertension, dyslipidemia, and micro-/macroalbuminuria were obtained from medical records. Logistic and linear regression models were used to assess factors associated with weight status.Of the 11,348 participants, 22 % were overweight and 14 % obese. Hypertension and dyslipidemia were diagnosed in 1.0 % and 3.8 % of participants, respectively; micro-/macroalbuminuria was diagnosed in 3.8 % of participants with available data (n = 7,401). The odds of either hypertension or dyslipidemia were higher in obese than healthy weight participants [OR 3.5, 99 % confidence interval (CI) 2.0-6.1 and 2.2, 99 % CI 1.6-3.1, respectively]. Obese participants tended to be diagnosed with micro-/macroalbuminuria less often than healthy weight participants (OR 0.6, 99 % CI 0.4-1.0).Obese children with type 1 diabetes have a higher prevalence of hypertension and dyslipidemia than healthy weight children with type 1 diabetes. The possible association of obesity with lower micro-/macroalbuminuria rates warrants further investigation.

    View details for DOI 10.1007/s00592-015-0785-1

    View details for PubMedID 26077171

  • Periodontal Microorganisms and Cardiovascular Risk Markers in Youth With Type 1 Diabetes and Without Diabetes JOURNAL OF PERIODONTOLOGY Merchant, A. T., Nahhas, G. J., Wadwa, R. P., Zhang, J., Tang, Y., Johnson, L. R., Maahs, D. M., Bishop, F., Teles, R., Morrato, E. H. 2016; 87 (4): 376-384

    Abstract

    A subset of periodontal microorganisms has been associated with cardiovascular disease (CVD), which is the leading complication of type 1 diabetes (t1DM). The authors therefore evaluated the association between periodontal microorganism groups and early markers of CVD in youth with t1DM.A cross-sectional analysis was conducted among youth aged 12 to 19 years at enrollment; 105 had t1DM for ≥5 years and were seeking care at the Barbara Davis Center, University of Colorado, from 2009 to 2011, and 71 did not have diabetes. Subgingival plaque samples were assessed for counts of 41 periodontal microorganisms using DNA-DNA hybridization. Microorganisms were classified using cluster analysis into four groups named red-orange, orange-green, blue/other, and yellow/other, modified from Socransky's color scheme for periodontal microorganisms. Subsamples (54 with t1DM and 48 without diabetes) also received a periodontal examination at the University of Colorado School of Dental Medicine.Participants were ≈15 years old on average, and 74% were white. Mean periodontal probing depth was 2 mm (SE 0.02), and 17% had bleeding on probing. In multivariable analyses, glycated hemoglobin (HbA1c) was inversely associated with the yellow/other cluster (microorganisms that are not associated with periodontal disease) among youth with t1DM. Blood pressure, triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol were not associated with microorganism clusters in this group. HbA1c was not associated with periodontal microorganism clusters among youth without diabetes.Among youth with t1DM who had good oral health, periodontal microorganisms were not associated with CVD risk factors.

    View details for DOI 10.1902/jop.2015.150531

    View details for Web of Science ID 000375842800008

    View details for PubMedID 26616842

  • Progress in Diabetes Technology: Developments in Insulin Pumps, Continuous Glucose Monitors, and Progress towards the Artificial Pancreas JOURNAL OF PEDIATRICS Forlenza, G. P., Buckingham, B., Maahs, D. M. 2016; 169: 13-20

    View details for DOI 10.1016/j.jpeds.2015.10.015

    View details for Web of Science ID 000368595300006

    View details for PubMedID 26547403

  • Development and Validation of a Method to Estimate Insulin Sensitivity in Patients With and Without Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Duca, L. M., Maahs, D. M., Schauer, I. E., Bergman, B. C., Nadeau, K. J., Bjornstad, P., Rewers, M., Snell-Bergeon, J. K. 2016; 101 (2): 686-695

    Abstract

    People with type 1 diabetes (T1D) have markedly reduced insulin sensitivity (IS) compared to their nondiabetic counterparts, and reduced IS is linked to higher cardiovascular risk.This study aimed to develop and validate an improved method for estimating IS in people with T1D.Prospective cohort.Adults (36 with T1D, 41 nondiabetic) were recruited from the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study for measurement of IS by hyperinsulinemic-euglycemic clamp to develop a clinically useful IS prediction equation (eIS) for T1D and nondiabetic individuals. These equations were then compared with previously published equations from the SEARCH and Pittsburgh Epidemiology of Diabetes Complications studies for the ability to predict measured IS in test sets of adults and adolescents from independent clamp studies.None.Comparison of clamp-measured IS to estimated IS.The best-fit prediction model (eIS) differed by diabetes status and included waist circumference, triglycerides, adiponectin, and diastolic blood pressure in all CACTI adults and insulin dose in adults with T1D (adjusted R(2) = 0.64) or fasting glucose and hemoglobin A1c (HbA1c) in nondiabetic adults (adjusted R(2) = 0.63). The eIS highly correlated with clamp-measured IS in all of the non-CACTI comparison populations (r = 0.83, P = .0002 in T1D adults; r = 0.71, P = .01 in nondiabetic adults; r = 0.44, P = .008 in T1D adolescents; r = 0.44, P = .006 in nondiabetic adolescents).eIS performed better than previous equations for estimating IS in individuals with and without T1D. These equations could simplify point-of-care assessment of IS to identify patients who could benefit from targeted intervention.

    View details for DOI 10.1210/jc.2015-3272

    View details for Web of Science ID 000378642700039

    View details for PubMedID 26672636

    View details for PubMedCentralID PMC4880115

  • Diabetes Technology and Therapy in the Pediatric Age Group DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Shalitin, S. 2016; 18: S86-S100

    View details for DOI 10.1089/dia.2016.2509

    View details for Web of Science ID 000369672600011

    View details for PubMedID 26836433

  • Therapeutic inertia: underdiagnosed and undertreated hypertension in children participating in the T1D Exchange Clinic Registry PEDIATRIC DIABETES Nambam, B., DuBose, S. N., Nathan, B. M., Beck, R. W., Maahs, D. M., Wadwa, R. P., Tamborlane, W. V., Foster, N. C., Miller, K. M., Haller, M. J. 2016; 17 (1): 15-20

    Abstract

    Reduction of cardiovascular risk in children with type 1 diabetes requires aggressive management of hypertension (HTN). However, the frequency of diagnosing and effectively treating HTN in youth with type 1 diabetes has not been established. To address this question, we used the data collected in >9000 youth with type 1 diabetes who enrolled in the T1D Exchange Clinic Registry.This analysis included data from medical records of 9362 individuals with enrolment and 1-yr follow-up visits (age 3 to <18 yr, disease duration ≥ 1 yr at follow-up). Data included the prevalence of a documented diagnosis of HTN, elevated blood pressure (BP) (systolic or diastolic ≥95th percentile for age, gender, and height), and treatment with angiotensin converting enzyme (ACE)-receptor inhibitor (ACE-I)/angiotensin receptor blocker (ARB) therapy.HTN was diagnosed in only 1% (113/9362) of participants; yet, elevated BP was recorded at one of the two visits in 17% and at both visits in 4%. Among those with diagnosed HTN, only 52% (59/113) were receiving ACE-I/ARB therapy and only 32% (19 of 59) of those treated were at goal BP. Children with diagnosed HTN had higher HbA1c (adjusted p < 0.001) and higher BMI (p < 0.001) when compared with children without HTN.HTN is likely under diagnosed and undertreated even in pediatric diabetes clinics. The relatively low proportion of hypertensive children receiving ACE-I therapy and reaching BP goals probably identifies an important area for improving care in children with type 1 diabetes.

    View details for DOI 10.1111/pedi.12231

    View details for Web of Science ID 000367723000002

    View details for PubMedID 25330905

  • Diabetic Kidney Disease in Adolescents With Type 2 Diabetes: New Insights and Potential Therapies CURRENT DIABETES REPORTS Bjornstad, P., Cherney, D. Z., Maahs, D. M., Nadeau, K. J. 2016; 16 (2)

    Abstract

    Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) and dialysis in the Western world. Early DKD, including microalbuminuria and renal hyperfiltration, is common in adolescents with type 2 diabetes (T2D). Furthermore, youth-onset T2D carries a higher risk of progressive DKD than adult-onset T2D of similar diabetes duration. DKD is characterized by a long clinically silent period without signs of disease. Therefore, a major challenge in preventing DKD is the difficulty in identifying high-risk T2D patients at an early stage. The Type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated a high initial prevalence that increased over time, irrespective of treatment arm. This key observation underscores the importance of discovering new therapeutic targets to supplement conventional management, in order to reduce DKD risk. In this review, we focus on early DKD in T2D and summarize potential novel biomarkers and therapeutic targets.

    View details for DOI 10.1007/s11892-015-0708-0

    View details for Web of Science ID 000370358200001

    View details for PubMedID 26803647

  • Profound hypokalemia associated with severe diabetic ketoacidosis PEDIATRIC DIABETES Davis, S. M., Maddux, A. B., Alonso, G. T., Okada, C. R., Mourani, P. M., Maahs, D. M. 2016; 17 (1): 61-65

    Abstract

    Hypokalemia is common during the treatment of diabetic ketoacidosis (DKA); however, severe hypokalemia at presentation prior to insulin treatment is exceedingly uncommon. A previously healthy 8-yr-old female presented with new onset type 1 diabetes mellitus, severe DKA (pH = 6.98), and profound hypokalemia (serum K = 1.3 mmol/L) accompanied by cardiac dysrhythmia. Insulin therapy was delayed for 9 h to allow replenishment of potassium to safe serum levels. Meticulous intensive care management resulted in complete recovery. This case highlights the importance of measuring serum potassium levels prior to initiating insulin therapy in DKA, judicious fluid and electrolyte management, as well as delaying and/or reducing insulin infusion rates in the setting of severe hypokalemia.

    View details for DOI 10.1111/pedi.12246

    View details for Web of Science ID 000367723000008

    View details for PubMedID 25430801

    View details for PubMedCentralID PMC4896141

  • Influences of gender on cardiovascular disease risk factors in adolescents with and without type 1 diabetes. International journal of pediatric endocrinology Brown, T. L., Maahs, D. M., Bishop, F. K., Snell-Bergeon, J. K., Wadwa, R. P. 2016; 2016: 8-?

    Abstract

    Women with type 1 diabetes (T1D) have a four-fold increased risk for cardiovascular disease (CVD) compared to non-diabetic (non-DM) women, as opposed to double the risk in T1D men compared to non-DM men. It is unclear how early in life CVD risk differences begin in T1D females. Therefore, our objective was to compare CVD risk factors in adolescents with and without T1D to determine the effects of gender on CVD risk factors.The study included 300 subjects with T1D (age 15.4±2.1 years, 50 % male, 80 % non-Hispanic White (NHW), glycated hemoglobin (A1c) 8.9±1.6 %, diabetes duration 8.8±3.0 years, BMI Z-score 0.62±0.77) and 100non-DM controls (age 15.4±2.1 years, 47 % male, 69 % NHW, BMI Z-score 0.29±1.04). CVD risk factors were compared by diabetes status and gender. Multivariate linear regression analyses were used to determine if relationships between diabetes status and CVD risk factors differed by gender independent of differences in A1c and BMI.Differences in CVD risk factors between T1D subjects and non-DM controls were more pronounced in girls. Compared to boys with T1D and non-DM girls, T1D girls had higher A1c (9.0 % vs. 8.6 % and 5.1 %, respectively), BMI Z-score (0.70 vs. 0.47 and 0.27), LDL-c (95 vs. 82 and 81 mg/dL), total cholesterol (171 vs. 153 and 150 mg/dL), DBP (68 vs. 67 and 63 mmHg), and hs-CRP (1.15 vs. 0.57 and 0.54 mg/dL) after adjusting for Tanner stage, smoking status, and race/ethnicity (p <0.05 for all). In T1D girls, differences in lipids, DBP, and hs-CRP persisted even after adjusting for centered A1c and BMI Z-score. Testing interactions between gender and T1D with CVD risk factors indicated that differences were greater between girls with T1D and non-DM compared to differences between boys with T1D and non-DM. Overall, observed increases in CVD risk factors in T1D girls remained after further adjustment for centered A1c or BMI Z-score.Interventions targeting CVD risk factors in addition to lowering HbA1c and maintaining healthy BMI are needed for youth with T1D. The increased CVD risk factors seen in adolescent girls with T1D in particular argues for earlier intervention to prevent later increased risk of CVD in women with T1D.

    View details for DOI 10.1186/s13633-016-0026-6

    View details for PubMedID 27099615

    View details for PubMedCentralID PMC4837565

  • Insulin delivery methods: Past, present and future. International journal of pharmaceutical investigation Shah, R. B., Patel, M., Maahs, D. M., Shah, V. N. 2016; 6 (1): 1-9

    Abstract

    Many patients with advanced type 2 diabetes mellitus (T2DM) and all patients with T1DM require insulin to keep blood glucose levels in the target range. The most common route of insulin administration is subcutaneous insulin injections. There are many ways to deliver insulin subcutaneously such as vials and syringes, insulin pens, and insulin pumps. Though subcutaneous insulin delivery is the standard route of insulin administration, it is associated with injection pain, needle phobia, lipodystrophy, noncompliance and peripheral hyperinsulinemia. Therefore, the need exists for delivering insulin in a minimally invasive or noninvasive and in most physiological way. Inhaled insulin was the first approved noninvasive and alternative way to deliver insulin, but it has been withdrawn from the market. Technologies are being explored to make the noninvasive delivery of insulin possible. Some of the routes of insulin administration that are under investigation are oral, buccal, nasal, peritoneal and transdermal. This review article focuses on the past, present and future of various insulin delivery techniques. This article has focused on different possible routes of insulin administration with its advantages and limitation and possible scope for the new drug development.

    View details for DOI 10.4103/2230-973X.176456

    View details for PubMedID 27014614

    View details for PubMedCentralID PMC4787057

  • Comparing Two Waist-to-Height Ratio Measurements with Cardiometabolic Risk Factors among Youth with Diabetes. International journal of child health and nutrition Liu, L. L., Kahn, H. S., Pettitt, D. J., Fino, N. F., Morgan, T., Maahs, D. M., Crimmins, N. A., Lamichhane, A. P., Liese, A. D., D'Agostino, R. B., Bell, R. A. 2016; 5 (3): 87-94

    Abstract

    Waist circumference (WC) is commonly measured by either the World Health Organization (WHO) or National Health and Nutrition Examination Survey (NHANES) protocol.Compare the associations of WHO vs. NHANES WC-to-height ratio (WHtR) protocols with cardiometabolic risk factors (CMRFs) in a sample of youth with diabetes.For youth (10-19 years old with type 1 [N=3082] or type 2 [N=533] diabetes) in the SEARCH for Diabetes in Youth Study, measurements were obtained of WC (by two protocols), weight, height, fasting lipids (total cholesterol, triglycerides, HDL cholesterol, Non-HDL cholesterol) and blood pressures. Associations of CMRFs with WHO and NHANES WHtR were modeled stratified by body mass index (BMI) percentiles for age/sex: lower BMI (<85(th) BMI percentile; N=2071) vs. higher BMI (≥85(th) percentile; N=1594).Among lower-BMI participants, both NHANES and WHO WHtR were associated (p<0.005) with all CMRFs except blood pressure. Among higher-BMI participants, both NHANES and WHO WHtR were associated (p<0.05) with all CMRFs. WHO WHtR was more strongly associated (p<0.05) than NHANES WHtR with triglycerides, non-HDL cholesterol, and systolic blood pressure in lower-BMI participants. Among high-BMI participants, WHO WHtR was more strongly associated (p<0.05) than NHANES WHtR with triglycerides and systolic blood pressure.Among youth with diabetes, WHtR calculated from either WC protocol captures cardiometabolic risk. The WHO WC protocol may be preferable to NHANES WC.

    View details for PubMedID 28232855

    View details for PubMedCentralID PMC5319429

  • Use of insulin pump therapy in children and adolescents with type 1 diabetes and its impact on metabolic control: comparison of results from three large, transatlantic paediatric registries DIABETOLOGIA Sherr, J. L., Hermann, J. M., Campbell, F., Foster, N. C., Hofer, S. E., Allgrove, J., Maahs, D. M., Kapellen, T. M., Holman, N., Tamborlane, W. V., Holl, R. W., Beck, R. W., Warner, J. T. 2016; 59 (1): 87-91

    Abstract

    While the use of insulin pumps in paediatrics has expanded dramatically, there is still considerable variability among countries in the use of pump technology. The present study sought to describe differences in metabolic control and pump use in young people with type 1 diabetes using data collected in three multicentre registries.Data for the years 2011 and 2012 from 54,410 children and adolescents were collected from the Prospective Diabetes Follow-up Registry (DPV; n = 26,198), T1D Exchange (T1DX; n = 13,755) and the National Paediatric Diabetes Audit (NPDA; n = 14,457). The modality of insulin delivery, based on age, sex and ethnic minority status, and the impact of pump use on HbA1c levels were compared.The overall mean HbA1c level was higher in the NPDA (8.9 ± 1.6% [74 ± 17.5 mmol/mol]) than in the DPV (8.0 ± 1.6% [64 ± 17.0 mmol/mol], p < 0.001) and T1DX (8.3 ± 1.4% [68 ± 15.4 mmol/mol], p < 0.001). Conversely, pump use was much lower in the NPDA (14%) than in the DPV (41%, p < 0.001) and T1DX (47%, p < 0.001). In a pooled analysis, pump use was associated with a lower mean HbA1c (pump: 8.0 ± 1.2% [64 ± 13.3 mmol/mol] vs injection: 8.5 ± 1.7% [69 ± 18.7 mmol/mol], p < 0.001). In all three registries, those with an ethnic minority status were less likely to be treated with a pump (p < 0.001) and boys were treated with a pump less often compared with girls (p < 0.001).Despite similar clinical characteristics and proportion of minority participants, substantial differences in metabolic control exist across the three large transatlantic registries of paediatric patients with type 1 diabetes, which appears to be due in part to the frequency of insulin pump therapy.

    View details for DOI 10.1007/s00125-015-3790-6

    View details for Web of Science ID 000365804500011

    View details for PubMedID 26546085

  • Rates of Diabetic Ketoacidosis: International Comparison With 49,859 Pediatric Patients With Type 1 Diabetes From England, Wales, the US, Austria, and Germany DIABETES CARE Maahs, D. M., Hermann, J. M., Holman, N., Foster, N. C., Kapellen, T. M., Allgrove, J., Schatz, D. A., Hofer, S. E., Campbell, F., Steigleder-Schweiger, C., Beck, R. W., Warner, J. T., Holl, R. W. 2015; 38 (10): 1876-1882

    Abstract

    Diabetic ketoacidosis (DKA) in children and adolescents with established type 1 diabetes is a major problem with considerable morbidity, mortality, and associated costs to patients, families, and health care systems. We analyzed data from three multinational type 1 diabetes registries/audits with similarly advanced, yet differing, health care systems with an aim to identify factors associated with DKA admissions.Data from 49,859 individuals <18 years with type 1 diabetes duration ≥1 year from the Prospective Diabetes Follow-up Registry (DPV) initiative (n = 22,397, Austria and Germany), the National Paediatric Diabetes Audit (NPDA; n = 16,314, England and Wales), and the T1D Exchange (T1DX; n = 11,148, U.S.) were included. DKA was defined as ≥1 hospitalization for hyperglycemia with a pH <7.3 during the prior year. Data were analyzed using multivariable logistic regression models.The frequency of DKA was 5.0% in DPV, 6.4% in NPDA, and 7.1% in T1DX, with differences persisting after demographic adjustment (P < 0.0001). In multivariable analyses, higher odds of DKA were found in females (odds ratio [OR] 1.23, 99% CI 1.10-1.37), ethnic minorities (OR 1.27, 99% CI 1.11-1.44), and HbA1c ≥7.5% (≥58 mmol/mol) (OR 2.54, 99% CI 2.09-3.09 for HbA1c from 7.5 to <9% [58 to <75 mmol/mol] and OR 8.74, 99% CI 7.18-10.63 for HbA1c ≥9.0% [≥75 mmol/mol]).These multinational data demonstrate high rates of DKA in childhood type 1 diabetes across three registries/audits and five nations. Females, ethnic minorities, and HbA1c above target were all associated with an increased risk of DKA. Targeted DKA prevention programs could result in substantial health care cost reduction and reduced patient morbidity and mortality.

    View details for DOI 10.2337/dc15-0780

    View details for Web of Science ID 000361840500023

    View details for PubMedID 26283737

  • Relation of Combined Non-High-Density Lipoprotein Cholesterol and Apolipoprotein B With Atherosclerosis in Adults With Type 1 Diabetes Mellitus AMERICAN JOURNAL OF CARDIOLOGY Bjornstad, P., Eckel, R. H., Pyle, L., Rewers, M., Maahs, D. M., Snell-Bergeon, J. K. 2015; 116 (7): 1057-1062

    Abstract

    Apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) are cardiovascular disease risk markers, although data in adults with type 1 diabetes mellitus (DM) are limited. We hypothesized that elevated apoB and non-HDL-C would be associated with greater odds of coronary artery calcification progression (CACp), a measure of coronary atherosclerosis, than either category alone in adults with type 1 DM. We grouped subjects with type 1 DM (n = 652) into 4 groups: elevated apoB (≥90 mg/dl) and elevated non-HDL-C (≥130 mg/dl), elevated non-HDL-C alone, elevated apoB alone, and normal apoB and non-HDL-C. We used logistic regression to examine the associations between the groups and CACp for a period of 6 years. We performed sensitivity analyses with elevated apoB and non-HDL-C redefined as at or more than the cohort means (91.4 and 119.0 mg/dl, respectively). Subjects with elevated apoB and non-HDL-C had greater odds of CACp compared with those with normal apoB and non-HDL-C (odds ratio 1.90, 95% confidence interval 1.15 to 3.15) and compared with subjects with elevated apoB alone (odds ratio 2.86, 95% confidence interval 1.43 to 5.74) adjusting for age, gender, duration, hemoglobin A1c, and statins. Similar results were obtained with elevated apoB and non-HDL-C defined as at or more than the cohort means. In conclusion, elevated apoB and non-HDL-C carry a greater risk of atherosclerosis than elevated apoB in the absence of elevated non-HDL-C in adults with type 1 DM. These data suggest that apoB and non-HDL-C should be viewed as complementary rather than competitive indexes of cardiovascular disease risk in type 1 DM.

    View details for DOI 10.1016/j.amjcard.2015.07.020

    View details for Web of Science ID 000362382400011

    View details for PubMedID 26251001

    View details for PubMedCentralID PMC4567927

  • Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with Type 1 diabetes NEPHROLOGY DIALYSIS TRANSPLANTATION Bjornstad, P., Cherney, D. Z., Snell-Bergeon, J. K., Pyle, L., Rewers, M., Johnson, R. J., Maahs, D. M. 2015; 30 (10): 1706-1711

    Abstract

    Rapid glomerular filtration rate (GFR) decline (>3 mL/min/1.73 m(2)) is an increasingly recognized high-risk diabetic nephropathy (DN) phenotype in Type 1 diabetes. Rapid GFR decline is a recognized predictor of impaired GFR (<60 mL/min/1.73 m(2)). However, the association between rapid GFR decline and renal hyperfiltration is not well described in Type 1 diabetes. We hypothesized that renal hyperfiltration (estimated glomerular filtration rate, eGFR ≥ 120 mL/min/1.73 m(2)) would predict rapid GFR decline over 6 years and that rapid GFR decline would predict impaired GFR at 6 years in adults with Type 1 diabetes.GFR was calculated by chronic kidney disease epidemiology (CKD-EPI) creatinine in 646 adults with Type 1 diabetes in the coronary artery calcification in Type 1 diabetes study. Logistic multivariable models were employed to investigate the relationships between renal hyperfiltration and rapid GFR decline, and rapid GFR decline and incident impaired GFR over 6 years.Renal hyperfiltration predicted greater odds of rapid GFR decline over 6 years [odds ratio (OR): 5.00, 95% confidence interval (CI): 3.03-8.25, P < 0.0001] adjusting for hemoglobin A1c (HbA1c), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), sex, duration, log of albumin/creatinine ratio and estimated insulin sensitivity. Furthermore, rapid GFR decline predicted greater odds of incident impaired eGFR (OR: 15.99, 95% CI 2.34-114.37, P = 0.006) in a similarly adjusted model. Sensitivity analyses with GFR calculated by CKD-EPI combined creatinine and cystatin C, and renal hyperfiltration defined as ≥135 mL/min/1.73 m(2) yielded similar results.In adults with Type 1 diabetes, rapid GFR decline over 6 years was associated with baseline renal hyperfiltration and incident GFR impairment. These observations may suggest an intermediate and predictive role of rapid GFR decline in the progression of DN.

    View details for DOI 10.1093/ndt/gfv121

    View details for Web of Science ID 000363171900015

    View details for PubMedID 26050268

    View details for PubMedCentralID PMC4838003

  • Update on Estimation of Kidney Function in Diabetic Kidney Disease CURRENT DIABETES REPORTS Bjornstad, P., Cherney, D. Z., Maahs, D. M. 2015; 15 (9)

    Abstract

    The American Diabetes Association recommends annual assessment of glomerular filtration rate (GFR) to screen for diabetic nephropathy. GFR is measured indirectly using markers that, ideally, are eliminated only by glomerular filtration. Measured GFR, although the gold standard, remains cumbersome and expensive. GFR is therefore routinely estimated using creatinine and/or cystatin C and clinical variables. In pediatrics, the Schwartz creatinine-based equation is most frequently used even though combined creatinine and cystatin C-based equations demonstrate stronger agreement with measured GFR. In adults, the CKD Epidemiology Collaboration (CKD-EPI) equations with creatinine and/or cystatin C are the most accurate and precise estimating equations. Despite recent advances, current estimates of GFR lack precision and accuracy before chronic kidney disease stage 3 (GFR < 60 mL/min/1.73 m(2)). There is therefore an urgent need to improve the methods for estimating and measuring GFR. In this review, we examine the current literature and data addressing measurement and estimation of GFR in diabetes.

    View details for DOI 10.1007/s11892-015-0633-2

    View details for Web of Science ID 000377953300001

    View details for PubMedID 26188736

  • Erratum. Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis. Diabetes Care 2015;38:1197-1204. Diabetes care Buckingham, B. A., Raghinaru, D., Cameron, F., Bequette, B. W., Chase, H. P., Maahs, D. M., Slover, R., Wadwa, R. P., Wilson, D. M., Ly, T., Aye, T., Hramiak, I., Clarson, C., Stein, R., Gallego, P. H., Lum, J., Sibayan, J., Kollman, C., Beck, R. W. 2015; 38 (9): 1813-?

    View details for DOI 10.2337/dc15-er09

    View details for PubMedID 26294776

  • Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis (vol 38, pg 1197, 2015) DIABETES CARE Buckingham, B. A., Raghinaru, D., Cameron, F., Bequette, B. W., Chase, H. P., Maahs, D. M., Slover, R., Wadwa, R. P., Wilson, D. M., Ly, T., Aye, T., Hramiak, I., Clarson, C., Stein, R., Gallego, P. H., Lum, J., Sibayan, J., Kollman, C., Beck, R. W. 2015; 38 (9): 1813-1813

    View details for DOI 10.2337/dc15-er09

    View details for Web of Science ID 000363416500037

  • Obesity in Youth with Type 1 Diabetes in Germany, Austria, and the United States JOURNAL OF PEDIATRICS Dubose, S. N., Hermann, J. M., Tamborlane, W. V., Beck, R. W., Dost, A., Dimeglio, L. A., Schwab, K. O., Holl, R. W., Hofer, S. E., Maahs, D. M. 2015; 167 (3): 627-?

    Abstract

    To examine the current extent of the obesity problem in 2 large pediatric clinical registries in the US and Europe and to examine the hypotheses that increased body mass index (BMI) z-scores (BMIz) are associated with greater hemoglobin A1c (HbA1c) and increased frequency of severe hypoglycemia in youth with type 1 diabetes (T1D).International (World Health Organization) and national (Centers for Disease Control and Prevention/German Health Interview and Examination Survey for Children and Adolescents) BMI references were used to calculate BMIz in participants (age 2-<18 years and ≥ 1 year duration of T1D) enrolled in the T1D Exchange (n = 11,435) and the Diabetes Prospective Follow-up (n = 21,501). Associations between BMIz and HbA1c and severe hypoglycemia were assessed.Participants in both registries had median BMI values that were greater than international and their respective national reference values. BMIz was significantly greater in the T1D Exchange vs the Diabetes Prospective Follow-up (P < .001). After stratification by age-group, no differences in BMI between registries existed for children 2-5 years, but differences were confirmed for 6- to 9-, 10- to 13-, and 14- to 17-year age groups (all P < .001). Greater BMIz were significantly related to greater HbA1c levels and more frequent occurrence of severe hypoglycemia across the registries, although these associations may not be clinically relevant.Excessive weight is a common problem in children with T1D in Germany and Austria and, especially, in the US. Our data suggest that obesity contributes to the challenges in achieving optimal glycemic control in children and adolescents with T1D.

    View details for DOI 10.1016/j.jpeds.2015.05.046

    View details for Web of Science ID 000363540200027

    View details for PubMedID 26164381

  • Fructose and uric acid in diabetic nephropathy DIABETOLOGIA Bjornstad, P., Lanaspa, M. A., Ishimoto, T., Kosugi, T., Kume, S., Jalal, D., Maahs, D. M., Snell-Bergeon, J. K., Johnson, R. J., Nakagawa, T. 2015; 58 (9): 1993-2002

    Abstract

    Clinical studies have reported associations between serum uric acid levels and the development of diabetic nephropathy, but the underlying mechanisms remain elusive. There is evidence from animal studies that blocking uric acid production protects the kidney from tubulointerstitial injury, which may suggest a causal role for uric acid in the development of diabetic tubular injury. In turn, when fructose, which is endogenously produced in diabetes via the polyol pathway, is metabolised, uric acid is generated from a side-chain reaction driven by ATP depletion and purine nucleotide turnover. For this reason, uric acid derived from endogenous fructose could cause tubulointerstitial injury in diabetes. Accordingly, our research group recently demonstrated that blocking fructose metabolism in a diabetic mouse model mitigated the development of tubulointerstitial injury by lowering tubular uric acid production. In this review we discuss the relationship between uric acid and fructose as a novel mechanism for the development of diabetic tubular injury.

    View details for DOI 10.1007/s00125-015-3650-4

    View details for Web of Science ID 000359268800004

    View details for PubMedID 26049401

    View details for PubMedCentralID PMC4826347

  • Adiponectin-SOGA Dissociation in Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Combs, T. P., Snell-Bergeon, J. K., Maahs, D. M., Bergman, B. C., Lamarche, M., Iberkleid, L., Abdelbaky, O., Tisch, R., Scherer, P. E., Marliss, E. B. 2015; 100 (8): E1065-E1073

    Abstract

    Circulating adiponectin is elevated in human type 1 diabetes (T1D) and nonobese diabetic (NOD) mice without the expected indications of adiponectin action, consistent with tissue resistance.Adiponectin stimulates hepatocyte production of the suppressor of glucose from autophagy (SOGA), a protein that inhibits glucose production. We postulated that due to tissue resistance, the elevation of adiponectin in T1D should fail to increase the levels of a surrogate marker for liver SOGA, the circulating C-terminal SOGA fragment.Liver and plasma SOGA were measured in NOD mice (n = 12) by Western blot. Serum adiponectin and SOGA were measured in T1D and control (Ctrl) participants undergoing a three-stage insulin clamp for the Coronary Artery Calcification in T1D study (n = 20). Glucose turnover was measured using 6,6[(2)H2]glucose (n = 12).In diabetic NOD mice, the 13%-29% decrease of liver SOGA (P = .003) and the 30%-37% reduction of circulating SOGA (P < .001) were correlated (r = 0.826; P = .001). In T1D serum, adiponectin was 50%-60% higher than Ctrl, SOGA was 30%-50% lower and insulin was 3-fold higher (P < .05). At the low insulin infusion rate (4 mU/m(2)·min), the resulting glucose appearance correlated negatively with adiponectin in T1D (r = -0.985, P = .002) and SOGA in Ctrl and T1D (r = -0.837, P = .001). Glucose disappearance correlated with adiponectin in Ctrl (r = -0.757, P = .049) and SOGA in Ctrl and T1D (r = -0.709, P = .010). At 40 mU/m(2)·min, the lowered glucose appearance was similar in Ctrl and T1D. Glucose disappearance increased only in Ctrl (P = .005), requiring greater glucose infusion to maintain euglycemia (8.58 ± 1.29 vs 3.09 ± 0.87 mg/kg·min; P = .009).The correlation between liver and plasma SOGA in NOD mice supports the use of the latter as surrogate marker for liver concentration. Reduced SOGA in diabetic NOD mice suggests resistance to adiponectin. The dissociation between adiponectin and SOGA in T1D raises the possibility that restoring adiponectin signaling and SOGA might improve the metabolic response to insulin therapy.

    View details for DOI 10.1210/jc.2015-1275

    View details for Web of Science ID 000364855900007

    View details for PubMedID 26052615

    View details for PubMedCentralID PMC4524989

  • Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Schanstra, J. P., Zuerbig, P., Alkhalaf, A., Argiles, A., Bakker, S. J., Beige, J., Bilo, H. J., Chatzikyrkou, C., Dakna, M., Dawson, J., Delles, C., Haller, H., Haubitz, M., Husi, H., Jankowski, J., Jerums, G., Kleefstra, N., Kuznetsova, T., Maahs, D. M., Menne, J., Mullen, W., Ortiz, A., Persson, F., Rossing, P., Ruggenenti, P., Rychlik, I., Serra, A. L., Siwy, J., Snell-Bergeon, J., Spasovski, G., Staessen, J. A., Vlahou, A., Mischak, H., Vanholder, R. 2015; 26 (8): 1999-2010

    Abstract

    Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.

    View details for DOI 10.1681/ASN.2014050423

    View details for Web of Science ID 000358895100024

    View details for PubMedID 25589610

    View details for PubMedCentralID PMC4520165

  • ISPAD Clinical Practice Consensus Guidelines 2014 Compendium: Type 2 diabetes in the child and adolescent (vol 15, pg 26, 2014) PEDIATRIC DIABETES Zeitler, P., Fu, J., Tandon, N., Nadeau, K., Urakami, T., Barrett, T., Maahs, D. 2015; 16 (5): 392-392

    View details for DOI 10.1111/pedi.12239

    View details for Web of Science ID 000357833800011

  • Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis DIABETES CARE Buckingham, B. A., Raghinaru, D., Cameron, F., Bequette, B. W., Chase, H. P., Maahs, D. M., Slover, R., Wadwa, R. P., Wilson, D. M., Ly, T., Aye, T., Hramiak, I., Clarson, C., Stein, R., Gallego, P. H., Lum, J., Sibayan, J., Kollman, C., Beck, R. W. 2015; 38 (7): 1197-1204

    Abstract

    Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system.In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight.Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis.In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher.

    View details for DOI 10.2337/dc14-3053

    View details for Web of Science ID 000356933600012

    View details for PubMedID 26049549

    View details for PubMedCentralID PMC4477332

  • Current State of Type 1 Diabetes Treatment in the US: Updated Data From the T1D Exchange Clinic Registry DIABETES CARE Miller, K. M., Foster, N. C., Beck, R. W., Bergenstal, R. M., DuBose, S. N., Dimeglio, L. A., Maahs, D. M., Tamborlane, W. V. 2015; 38 (6): 971-978

    Abstract

    To examine the overall state of metabolic control and current use of advanced diabetes technologies in the U.S., we report recent data collected on individuals with type 1 diabetes participating in the T1D Exchange clinic registry. Data from 16,061 participants updated between 1 September 2013 and 1 December 2014 were compared with registry enrollment data collected from 1 September 2010 to 1 August 2012. Mean hemoglobin A1c (HbA1c) was assessed by year of age from <4 to >75 years. The overall average HbA1c was 8.2% (66 mmol/mol) at enrollment and 8.4% (68 mmol/mol) at the most recent update. During childhood, mean HbA1c decreased from 8.3% (67 mmol/mol) in 2-4-year-olds to 8.1% (65 mmol/mol) at 7 years of age, followed by an increase to 9.2% (77 mmol/mol) in 19-year-olds. Subsequently, mean HbA1c values decline gradually until ∼30 years of age, plateauing at 7.5-7.8% (58-62 mmol/mol) beyond age 30 until a modest drop in HbA1c below 7.5% (58 mmol/mol) in those 65 years of age. Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) remain all too common complications of treatment, especially in older (SH) and younger patients (DKA). Insulin pump use increased slightly from enrollment (58-62%), and use of continuous glucose monitoring (CGM) did not change (7%). Although the T1D Exchange registry findings are not population based and could be biased, it is clear that there remains considerable room for improving outcomes of treatment of type 1 diabetes across all age-groups. Barriers to more effective use of current treatments need to be addressed and new therapies are needed to achieve optimal metabolic control in people with type 1 diabetes.

    View details for DOI 10.2337/dc15-0078

    View details for Web of Science ID 000362969000015

    View details for PubMedID 25998289

  • Diabetes Complications in Childhood Diabetes-New Biomarkers and Technologies. Current pediatrics reports Bjornstad, P., Maahs, D. M. 2015; 3 (2): 177-186

    Abstract

    A major challenge in preventing vascular complications in diabetes is the inability to identify high-risk patients at an early stage, emphasizing the importance of discovering new risk factors, technologies and therapeutic targets to reduce the development and progression of complications. Promising biomarkers which may improve risk stratification and serve as therapeutic targets, include: uric acid, insulin sensitivity, copeptin, SGLT-2 and Klotho/FGF-23. Non-invasive measures of macrovasuclar disease in youth, include: 1) pulse wave velocity to examine arterial stiffness; 2) carotid intima-media thickness to evaluate arterial thickness; 3) cardiac MRI to investigate cardiac function and structure. Novel microvascular measures include: GFR by iohexol clearance using filter paper to directly measure GFR, retinal vascular geometry to predict early retinal changes and corneal confocal microscopy to improve detection of early nerve loss to better predict diabetic neuropathy. Herein we will review technologies, novel biomarkers, and therapeutic targets in relation to vascular complications of diabetes.

    View details for PubMedID 26425403

    View details for PubMedCentralID PMC4584153

  • Flexible Lifestyles for Youth (FL3X) behavioural intervention for at-risk adolescents with Type 1 diabetes: a randomized pilot and feasibility trial DIABETIC MEDICINE Mayer-Davis, E. J., Seid, M., CRANDELL, J., Dolan, L., Lagarde, W. H., Letourneau, L., Maahs, D. M., Marcovina, S., Nachreiner, J., Standiford, D., Thomas, J., Wysocki, T. 2015; 32 (6): 829-833

    Abstract

    To determine the potential effect sizes for the Flexible Lifestyle for Youth (FL3X) behavioural intervention to improve glycaemic control (HbA(1c)) and quality of life for at-risk adolescents with Type 1 diabetes.Participants [n = 61; age 12-16 years, HbA(1c) 64-119 mmol/mol (8-13%)] were randomized to FL3X (minimum three sessions) or usual care. Effect sizes (Cohen's d), comparing the mean difference between the groups, were calculated.Study retention (95%), attendance at intervention sessions (87% attended all three sessions) and acceptability were high (100% of the adolescents and 91% of parents would recommend the programme to others). Overall, 41% of participants in the intervention group and 24% of participants in the control group were 'responders' [HbA(1c) decreased by > 6 mmol/mol (0.5%); d = 0.37]. HbA(1c) levels decreased (d = -0.18), diabetes-specific quality of life increased (d = 0.29), but generic quality of life decreased (d = -0.23) in the intervention compared with the control group.The FL3X programme merits further study for improving HbA(1c) and diabetes-specific quality of life in adolescents with Type 1 diabetes. (Clinical trials registry no.: NCT01286350).

    View details for DOI 10.1111/dme.12641

    View details for Web of Science ID 000354637600019

    View details for PubMedID 25424501

    View details for PubMedCentralID PMC4437823

  • Change in adiposity minimally affects the lipid profile in youth with recent onset type 1 diabetes PEDIATRIC DIABETES Shah, A. S., Dolan, L. M., Dabelea, D., Stafford, J. M., D'Agostino, R. B., Mayer-Davis, E. J., Marcovina, S., Imperatore, G., Wadwa, R. P., Daniels, S. R., Reynolds, K., Hamman, R. F., Bowlby, D. A., Maahs, D. M. 2015; 16 (4): 280-286

    Abstract

    Dyslipidemia contributes to the increased risk of cardiovascular disease in persons with type 1 diabetes (T1D). Weight control is commonly recommended as a treatment for dyslipidemia. However, the extent to which decreases in weight affect the lipid profile in youth with T1D is not known. Therefore, we tested the hypothesis that decreases in body mass index z-score (BMIz) were associated with concomitant changes in the lipid profile in youth with T1D.We studied 1142 youth with incident T1D, who had at least two fasting lipid measurements over 2 yr (initial visit mean: age = 10.8 ± 3.9 yr, BMIz = 0.55 ± 0.97, T1D duration = 10.7 ± 7.6 months; 47.5% female, 77.9% non-Hispanic white) in the SEARCH for Diabetes in Youth Study. Longitudinal mixed models were used to examine the relationships between changes in BMIz and changes in total, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, and log triglycerides (TG) adjusted for initial age, sex, race/ethnicity, clinical site, season of study visit, T1D duration, and glycated hemoglobin A1c (HbA1c).We found that over 2 yr all lipid levels, except LDL-C, increased significantly (p < 0.05). Decreases in BMIz were associated with favorable changes in HDL-C and TG only and the magnitude of these changes depended on the initial BMIz value (interaction p < 0.05), so that greater improvements were seen in those with higher BMIz.Our data suggest that weight loss may be an effective, but limited, therapeutic approach for dyslipidemia in youth with T1D.

    View details for DOI 10.1111/pedi.12162

    View details for Web of Science ID 000354123300006

    View details for PubMedID 25099744

    View details for PubMedCentralID PMC4320680

  • Association of apolipoprotein B, LDL-C and vascular stiffness in adolescents with type 1 diabetes ACTA DIABETOLOGICA Bjornstad, P., Nhung Nguyen, N., Reinick, C., Maahs, D. M., Bishop, F. K., Clements, S. A., Snell-Bergeon, J. K., Lieberman, R., Pyle, L., Daniels, S. R., Wadwa, R. P. 2015; 52 (3): 611-619

    Abstract

    LDL cholesterol (LDL-C) is the current lipid standard for cardiovascular disease (CVD)-risk assessment in type 1 diabetes. Apolipoprotein B (apoB) may be helpful to further stratify CVD risk. We explored the association between apoB and pulse wave velocity (PWV) to determine if apoB would improve CVD-risk stratification, especially in type 1 diabetes adolescents with borderline LDL-C (100-129 mg/dL). We hypothesized that type 1 diabetes adolescents with borderline LDL-C and elevated apoB (≥90 mg/dL) would have increased PWV compared to those with borderline LDL-C and normal apoB (<90 mg/dL), and that apoB would explain more of the variability of PWV than alternative lipid indices.Fasting lipids, including apoB, were collected in 267 adolescents, age 12-19 years, with diabetes duration >5 years and HbA1c 8.9 ± 1.6 %. Triglyceride to HDL-C ratio (TG/HDL-C) and nonHDL-cholesterol (nonHDL-C) were calculated. PWV was measured in the carotid-femoral segment.ApoB, nonHDL-C and TG/HDL-C correlated with PWV (p < 0.0001). ApoB, nonHDL-C and TG/HDL-C remained significantly associated with PWV in fully adjusted models. In adolescents with borderline LDL-C (n = 61), PWV was significantly higher in those with elevated apoB than in those with normal apoB (5.6 ± 0.6 vs. 5.2 ± 0.6 m/s, p < 0.01) and also remained significant after adjustment for CVD-risk factors (p = 0.0002). Moreover, in those with borderline LDL-C, apoB explained more of the variability of PWV than nonHDL-C and TG/HDL-C.Elevated apoB is associated with increased arterial stiffness in type 1 diabetes adolescents. Measurement of apoB in addition to LDL-C may be helpful in stratifying CVD risk in type 1 diabetes adolescents, especially in those with borderline LDL-C.

    View details for DOI 10.1007/s00592-014-0693-9

    View details for Web of Science ID 000355233500021

    View details for PubMedID 25539881

    View details for PubMedCentralID PMC4449793

  • Factors Associated with Nocturnal Hypoglycemia in At-Risk Adolescents and Young Adults with Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Wilson, D. M., Calhoun, P. M., Maahs, D. M., Chase, H. P., Messer, L., Buckingham, B. A., Aye, T., Clinton, P. K., Hramiak, I., Kollman, C., Beck, R. W. 2015; 17 (6): 385-391

    Abstract

    Hypoglycemia remains an impediment to good glycemic control, with nocturnal hypoglycemia being particularly dangerous. Information on major contributors to nocturnal hypoglycemia remains critical for understanding and mitigating risk.Continuous glucose monitoring (CGM) data for 855 nights were studied, generated by 45 subjects 15-45 years of age with hemoglobin A1c (HbA1c) levels of ≤8.0% who participated in a larger randomized study. Factors assessed for potential association with nocturnal hypoglycemia (CGM measurement of <60 mg/dL for ≥30 min) included bedtime blood glucose (BG), exercise intensity, bedtime snack, insulin on board, day of the week, previous daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal insulin, and daily insulin dose.Hypoglycemia occurred during 221 of 885 (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend for lower bedtime BG levels to be associated with more frequent nocturnal hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend versus weekday, gender, and daily basal and bolus insulin were not associated with nocturnal hypoglycemia.Awareness that HbA1c level, exercise, bedtime BG level, and daytime hypoglycemia are all modifiable factors associated with nocturnal hypoglycemia may help patients and providers decrease the risk of hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear fashion across the range of variables, with no clear-cut thresholds to guide clinicians or patients for any particular night.

    View details for DOI 10.1089/dia.2014.0342

    View details for Web of Science ID 000354168400005

    View details for PubMedID 25761202

    View details for PubMedCentralID PMC4432491

  • Refining the Closed Loop in the Data Age: Research-to-Practice Transitions in Diabetes Technology DIABETES TECHNOLOGY & THERAPEUTICS Forlenza, G. P., Sankaranarayanan, S., Maahs, D. M. 2015; 17 (5): 304-306

    View details for DOI 10.1089/dia.2015.0055

    View details for Web of Science ID 000353485700002

    View details for PubMedID 25844981

  • Response to comment on Wong et al. Real-time continuous glucose monitoring among participants in the T1D exchange clinic registry. Diabetes Care 2014;37:2702-2709. Diabetes care Wong, J. C., Foster, N. C., Maahs, D. M., Raghinaru, D., Bergenstal, R. M., Ahmann, A. J., Peters, A. L., Bode, B. W., Aleppo, G., Hirsch, I. B., Kleis, L., Chase, H. P., DuBose, S. N., Miller, K. M., Beck, R. W., Adi, S. 2015; 38 (4)

    View details for DOI 10.2337/dc14-2782

    View details for PubMedID 25805875

  • DIABETES Elevated risk of mortality in type 1 diabetes mellitus NATURE REVIEWS ENDOCRINOLOGY Snell-Bergeon, J. K., Maahs, D. M. 2015; 11 (3): 136-137

    View details for DOI 10.1038/nrendo.2014.245

    View details for Web of Science ID 000349892000004

    View details for PubMedID 25583696

  • Insulin sensitivity and complications in type 1 diabetes: New insights. World journal of diabetes Bjornstad, P., Snell-Bergeon, J. K., Nadeau, K. J., Maahs, D. M. 2015; 6 (1): 8-16

    Abstract

    Despite improvements in glucose, lipids and blood pressure control, vascular complications remain the most important cause of morbidity and mortality in patients with type 1 diabetes. For that reason, there is a need to identify additional risk factors to utilize in clinical practice or translate to novel therapies to prevent vascular complications. Reduced insulin sensitivity is an increasingly recognized component of type 1 diabetes that has been linked with the development and progression of both micro- and macrovascular complications. Adolescents and adults with type 1 diabetes have reduced insulin sensitivity, even when compared to their non-diabetic counterparts of similar adiposity, serum triglycerides, high-density lipoprotein cholesterol, level of habitual physical activity, and in adolescents, pubertal stage. Reduced insulin sensitivity is thought to contribute both to the initiation and progression of macro- and microvascular complications in type 1 diabetes. There are currently clinical trials underway examining the benefits of improving insulin sensitivity with regards to vascular complications in type 1 diabetes. Reduced insulin sensitivity is an increasingly recognized component of type 1 diabetes, is implicated in the pathogenesis of vascular complications and is potentially an important therapeutic target to prevent vascular complications. In this review, we will focus on the pathophysiologic contribution of insulin sensitivity to vascular complications and summarize related ongoing clinical trials.

    View details for DOI 10.4239/wjd.v6.i1.8

    View details for PubMedID 25685274

    View details for PubMedCentralID PMC4317319

  • Achieving International Society for Pediatric and Adolescent Diabetes and American Diabetes Association clinical guidelines offers cardiorenal protection for youth with type 1 diabetes. Pediatric diabetes Bjornstad, P., Pyle, L., Nguyen, N., Snell-Bergeon, J. K., Bishop, F. K., Wadwa, R. P., Maahs, D. M. 2015; 16 (1): 22-30

    Abstract

    Most youth with type 1 diabetes do not meet the American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) targets for hemoglobin A1c (HbA1c), blood pressure (BP), lipids, and body mass index (BMI). We hypothesized that ISPAD/ADA goal achievement at baseline would be associated with cardiorenal risk factors at baseline and 2 yr follow-up in adolescents with type 1 diabetes.We assessed the cross-sectional and longitudinal relationships between ISPAD/ADA goal achievement at baseline and cardiorenal health at baseline and 2-yr follow-up (n = 297; 15.4 ± 2.1 yr at baseline) in adolescents with type 1 diabetes. Goal achievement was defined as HbA1c < 7.5%, BP < 90th percentile for age, sex, and height, low density lipoprotein-cholesterol (LDL-C) <100 mg/dL, high density lipoprotein-cholesterol (HDL-C) >35 mg/dL, triglycerides (TG) <150 mg/dL and BMI <85th percentile for age and sex. Cardiorenal outcomes included pulse-wave velocity (PWV), brachial distensibility (BrachD), augmentation index (AIx), and epidermal growth factor receptor (eGFR) continuously and categorically as hyperfiltration (eGFR ≥ 135 mL/min/1.73 m(2)).Adolescents with type 1 diabetes who met 1-3 goals, had significantly greater (P < 0.05) baseline PWV (5.1 ± 0.1 vs. 5.4 ± 0.1 m/s), follow-up PWV (5.5 ± 0.1 vs. 5.7 ± 0.1 m/s), greater follow-up eGFR (104 ± 2 vs. 116 ± 3 mL/min/1.73 m(2)), and greater odds of renal hyperfiltration at follow-up (odds ratio (OR): 20.0, 95% confidence interval (CI): 3.8-105.2) compared to those who met 4-6 goals after adjusting for Tanner stage, sex, age, and diabetes duration. No statistically significant differences in the cardiorenal outcomes were observed between adolescents with type 1 diabetes who met 4-6 goals and non-diabetic controls (n = 96).In adolescents with type 1 diabetes, baseline ADA/ISPAD goal achievement was associated with cardiorenal protection at baseline and 2-yr follow-up.

    View details for DOI 10.1111/pedi.12252

    View details for PubMedID 25604668

  • Achieving International Society for Pediatric and Adolescent Diabetes and American Diabetes Association clinical guidelines offers cardiorenal protection for youth with type 1 diabetes PEDIATRIC DIABETES Bjornstad, P., Pyle, L., Nhung Nguyen, N., Snell-Bergeon, J. K., Bishop, F. K., Wadwa, R. P., Maahs, D. M. 2015; 16 (1): 22-30

    View details for DOI 10.1111/pedi.12252

    View details for Web of Science ID 000348768500004

  • Estimated insulin sensitivity predicts regression of albuminuria in Type 1 diabetes DIABETIC MEDICINE Bjornstad, P., Maahs, D. M., JOHNSON, R. J., Rewers, M., Snell-Bergeon, J. K. 2015; 32 (2): 257-261

    Abstract

    To test the hypothesis that greater baseline insulin sensitivity would predict regression of albuminuria over 6 years in adults with Type 1 diabetes.We enrolled 81 people aged 30-48 years with albuminuria at baseline in the present study and re-examined them 6 years later. Urinary albumin excretion rate was measured and albuminuria was defined as urinary albumin excretion rate ≥ 20 μg/min. Regression of albuminuria was defined as normoalbuminuria (urinary albumin excretion rate < 20 μg/min) at follow-up. Predictors of regression of albuminuria were examined in stepwise logistic regression. The variables age, diabetes duration, sex, serum uric acid, HbA1c , systolic blood pressure, LDL cholesterol, HDL cholesterol, BMI, baseline albumin excretion rate, estimated insulin sensitivity at baseline, change in estimated insulin sensitivity from baseline to follow-up and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were considered for inclusion in the model.Estimated insulin sensitivity was significantly higher at both baseline (4.6 ± 1.2 vs 3.4 ± 1.7; P = 0.002) and follow-up (5.2 ± 1.9 vs. 3.5 ± 1.7; P < 0.0001) in people who had regression of albuminuria vs those who did not. HbA1c (odds ratio 0.4, 95% CI 0.2-0.8; P = 0.006), estimated insulin sensitivity (odds ratio 2.5, 95% CI 1.3-4.9; P = 0.006) at baseline and change in estimated insulin sensitivity from baseline to follow-up (odds ratio 2.7, 95% CI 1.4-5.3; P = 0.003) were independently associated with regression of albuminuria in a multivariable stepwise model.In conclusion, over 6 years, higher baseline estimated insulin sensitivity and change in estimated insulin sensitivity independently predicted regression of albuminuria. Improving insulin sensitivity in people with Type 1 diabetes is a potential therapeutic target to increase rates of regression of albuminuria.

    View details for DOI 10.1111/dme.12572

    View details for Web of Science ID 000348515500017

    View details for PubMedID 25303233

    View details for PubMedCentralID PMC4301993

  • Renal Function Is Associated With Peak Exercise Capacity in Adolescents With Type 1 Diabetes DIABETES CARE Bjornstad, P., Cree-Green, M., Baumgartner, A., Maahs, D. M., Cherney, D. Z., Pyle, L., Regensteiner, J. G., Reusch, J. E., Nadeau, K. J. 2015; 38 (1): 126-131

    Abstract

    Diabetic nephropathy and cardiovascular disease are strongly related in adults with type 1 diabetes, yet little is known about this relationship in adolescents prior to the onset of detectable clinical disease. We hypothesized that cardiopulmonary fitness would be directly associated with albumin-to-creatinine ratio (ACR) and inversely related to estimated glomerular filtration rate (eGFR) in adolescents with type 1 diabetes.Sixty-nine adolescents with type 1 diabetes and 13 nondiabetic control subjects of similar pubertal stage and BMI had insulin sensitivity (glucose infusion rate [GIR]), measured by hyperinsulinemic-euglycemic clamp, and lean body mass, measured by DEXA. Cardiopulmonary fitness was measured by cycle ergometry to obtain peak volume of oxygen (VO2peak), and renal function was measured by eGFR using the Bouvet equation (measuring creatinine and cystatin C levels) and ACR.Adolescents (15.5 ± 2.2 years of age) with type 1 diabetes (6.3 ± 3.8 years diabetes duration) had reduced VO2peak (31.5 ± 6.3 vs. 36.2 ± 7.9 mL/kg ⋅ min, P = 0.046) and VO2peak/lean kg (43.7 ± 7.0 vs. 51.0 ± 8.6 mL/lean kg ⋅ min, P = 0.007) compared with nondiabetic control subjects. eGFR was inversely associated with VO2peak and VO2peak/lean kg after adjusting for sex, Tanner stage, GIR, HbA1c level, systolic blood pressure, and LDL cholesterol level (β ± SE, VO2peak: -0.19 ± 0.07, P = 0.02; VO2peak/lean kg: -0.19 ± 0.09, P = 0.048). Moreover, participants in the highest tertile for eGFR had significantly lower sex- and Tanner-adjusted VO2peak and VO2peak/lean kg compared with participants in the lowest tertile.Adolescents with type 1 diabetes had reduced exercise capacity, which was strongly associated with renal health, independent of insulin sensitivity. Future studies should examine the underlying interrelated pathophysiology in order to identify probable targets for treatment to reduce cardiovascular and renal complications.

    View details for DOI 10.2337/dc14-1742

    View details for Web of Science ID 000346762300024

    View details for PubMedID 25414156

    View details for PubMedCentralID PMC4274775

  • Towards a Verified Artificial Pancreas: Challenges and Solutions for Runtime Verification RUNTIME VERIFICATION, RV 2015 Cameron, F., Fainekos, G., Maahs, D. M., Sankaranarayanan, S. 2015; 9333: 3-17
  • Plasma triglycerides predict incident albuminuria and progression of coronary artery calcification in adults with type 1 diabetes: The Coronary Artery Calcification in Type 1 Diabetes Study JOURNAL OF CLINICAL LIPIDOLOGY Bjornstad, P., Maahs, D. M., Wadwa, R. P., Pyle, L., Rewers, M., Eckel, R. H., Snell-Bergeon, J. K. 2014; 8 (6): 576-583

    Abstract

    Coronary artery disease and diabetic nephropathy, which are thought to share pathogenic mechanisms, remain the most common causes of mortality in type 1 diabetes (T1D). Data from basic and clinical studies indicate that hypertriglyceridemia plays an important role in the pathogenesis of vascular complications, but the role of triglycerides (TG) in the normal range remains unresolved in T1D.We hypothesized that fasting TG would independently predict cardiorenal disease in adults with T1D and normal-to-low levels of TG.Subjects (N = 652) were 19 to 56 years old at baseline and reexamined 6 years later. Urinary albumin excretion was measured, and categorized as microalbuminuria or greater. Progression of coronary artery calcification (CACp), measured using electron beam computed tomography, was defined as a change in the square root transformed CAC volume ≥2.5. The association of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, non-HDL-C, natural log triglyceride (lnTG), ln(TG/HDL-C) ratio with CACp and incident albuminuria were examined in logistic regression. The models were adjusted for age, sex, T1D duration, hemoglobin A1c, systolic blood pressure, diastolic blood pressure, blood pressure medications, statins, and smoking status. Integrated discrimination index and net reclassification improvement were used to examine prediction performance.Incident albuminuria was independently associated with CACp. lnTG independently predicted both incident albuminuria (odds ratio: 1.53, 1.02-2.30, P = .04) and CACp (1.41, 1.11-1.80, P = .006). The addition of lnTG to ABC risk factors (HbA1c, systolic blood pressure, diastolic blood pressure, and LDL-C) moderately improved discrimination and reclassification of CACp and incident albuminuria.In adults with T1D, fasting TG independently predicted cardiorenal disease over 6 years and improved reclassification of risk by conventional risk factors.

    View details for DOI 10.1016/j.jacl.2014.08.008

    View details for Web of Science ID 000346880900008

    View details for PubMedID 25499940

    View details for PubMedCentralID PMC4268486

  • Insulin Sensitivity Is an Important Determinant of Renal Health in Adolescents With Type 2 Diabetes DIABETES CARE Bjornstad, P., Maahs, D. M., Cherney, D. Z., Cree-Green, M., West, A., Pyle, L., Nadeau, K. J. 2014; 37 (11): 3033-3039

    Abstract

    Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease and is a major cause of mortality in type 2 diabetes. Insulin sensitivity is an important determinant of renal health in adults with type 2 diabetes, but limited data exist in adolescents. We hypothesized that measured insulin sensitivity (glucose infusion rate [GIR]) would be associated with early markers of DN reflected by estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in adolescents with type 2 diabetes.Type 2 diabetic (n = 46), obese (n = 29), and lean (n = 19) adolescents (15.1 ± 2.2 years) had GIR measured by hyperinsulinemic-euglycemic clamps. ACR was measured and GFR was estimated by the Bouvet equation (combined creatinine and cystatin C).Adolescents with type 2 diabetes had significantly lower GIR, and higher eGFR and ACR than obese or lean adolescents. Moreover, 34% of type 2 diabetic adolescents had albuminuria (ACR ≥30 mg/g), and 24% had hyperfiltration (≥135 mL/min/1.73 m2). Stratifying ACR and eGFR into tertiles, adolescents with type 2 diabetes in the highest tertiles of ACR and eGFR had respectively lower GIR than those in the mid and low tertiles, after adjusting for age, sex, Tanner stage, BMI, and HbA1c (P = 0.02 and P = 0.04). GIR, but not HbA1c, LDL, or systolic blood pressure, was also associated with eGFR after adjusting for sex and Tanner stage (β ± SE: -2.23 ± 0.87; P = 0.02).A significant proportion of adolescents with type 2 diabetes showed evidence of early DN, and insulin sensitivity, rather than HbA1c, blood pressure, or lipid control, was the strongest determinant of renal health.

    View details for DOI 10.2337/dc14-1331

    View details for Web of Science ID 000343588500032

    View details for PubMedID 25071077

    View details for PubMedCentralID PMC4207204

  • ABC goal achievement predicts microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes: The Coronary Artery Calcification in Type 1 Diabetes Study JOURNAL OF DIABETES AND ITS COMPLICATIONS Bjornstad, P., Maahs, D. M., Rewers, M., Johnson, R. J., Snell-Bergeon, J. K. 2014; 28 (6): 762-766

    Abstract

    Vascular complications of type 1 diabetes are thought to cluster. We examined the prevalence and incidence of vascular complications and American Diabetes Association's ABC goal achievements in a prospective cohort of adults with type 1 diabetes. We hypothesized that ABC achievement at baseline would predict both micro- and macrovascular complications over 6-years.Participants (N=652) were 19-56 year old at baseline and re-examined 6-years later. Microvascular complications included diabetic nephropathy (DN), defined as incident albuminuria (AER≥20 μg/min) or rapid GFR decline (>3.3%/year) by CKD-EPI cystatin C and proliferative diabetic retinopathy (PDR), defined as laser eye-therapy. Macrovascular complications were defined as coronary artery calcium progression (CACp), measured by electron-beam computed-tomography. ABC goals were defined as HbA1c<7.0%, BP<130/80 mmHg and LDL-C<100mg/dL.ABC control was suboptimal with only 6% meeting all goals. Meeting no ABC goals at baseline compared to meeting all goals was associated with increased odds of developing microvascular complications (OR: 8.5, 2.3-31.5, p=0.001), but did not reach significance for CACp (OR: 1.7, 0.8-3.9, p=0.19).ABC achievement at baseline strongly predicted microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes, suggesting a need for novel therapeutic targets to complement conventional risk factors in treating macrovascular complications.

    View details for DOI 10.1016/j.jdiacomp.2014.06.017

    View details for Web of Science ID 000344981200004

    View details for PubMedID 25270733

    View details for PubMedCentralID PMC4252593

  • A novel method to detect pressure-induced sensor attenuations (PISA) in an artificial pancreas. Journal of diabetes science and technology Baysal, N., Cameron, F., Buckingham, B. A., Wilson, D. M., Chase, H. P., Maahs, D. M., Bequette, B. W. 2014; 8 (6): 1091-1096

    Abstract

    Continuous glucose monitors (CGMs) provide real-time interstitial glucose concentrations that are essential for automated treatment of individuals with type 1 diabetes. Miscalibration, noise spikes, dropouts, or pressure applied to the site (e.g., lying on the site while sleeping) can cause inaccurate glucose signals, which could lead to inappropriate insulin dosing decisions. These studies focus on the problem of pressure-induced sensor attenuations (PISAs) that occur overnight and can cause undesirable pump shut-offs in a predictive low glucose suspend system. The algorithm presented here uses real-time CGM readings without knowledge of meals, insulin doses, activity, sensor recalibrations, or fingerstick measurements. The real-time PISA detection technique was tested on outpatient "in-home" data from a predictive low-glucose suspend trial with over 1125 nights of data. A total of 178 sets were created by using different parameters for the PISA detection algorithm to illustrate its range of available performance. The tracings were reviewed via a web-based analysis tool by an engineer with an extensive expertise on analyzing clinical datasets and ~3% of the CGM readings were marked as PISA events which were used as the gold standard. It is shown that 88.34% of the PISAs were successfully detected by the algorithm, and the percentage of false detections could be reduced to 1.70% by altering the algorithm parameters. Use of the proposed PISA detection method can result in a significant decrease in undesirable pump suspensions overnight, and may lead to lower overnight mean glucose levels while still achieving a low risk of hypoglycemia.

    View details for DOI 10.1177/1932296814553267

    View details for PubMedID 25316716

    View details for PubMedCentralID PMC4455457

  • Predicting major outcomes in type 1 diabetes: a model development and validation study DIABETOLOGIA Soedamah-Muthu, S. S., Vergouwe, Y., Costacou, T., Miller, R. G., Zgibor, J., Chaturvedi, N., Snell-Bergeon, J. K., Maahs, D. M., Rewers, M., Forsblom, C., Harjutsalo, V., Groop, P., Fuller, J. H., Moons, K. G., Orchard, T. J. 2014; 57 (11): 2304-2314

    Abstract

    Type 1 diabetes is associated with a higher risk of major vascular complications and death. A reliable method that predicted these outcomes early in the disease process would help in risk classification. We therefore developed such a prognostic model and quantified its performance in independent cohorts.Data were analysed from 1,973 participants with type 1 diabetes followed for 7 years in the EURODIAB Prospective Complications Study. Strong prognostic factors for major outcomes were combined in a Weibull regression model. The performance of the model was tested in three different prospective cohorts: the Pittsburgh Epidemiology of Diabetes Complications study (EDC, n = 554), the Finnish Diabetic Nephropathy study (FinnDiane, n = 2,999) and the Coronary Artery Calcification in Type 1 Diabetes study (CACTI, n = 580). Major outcomes included major CHD, stroke, end-stage renal failure, amputations, blindness and all-cause death.A total of 95 EURODIAB patients with type 1 diabetes developed major outcomes during follow-up. Prognostic factors were age, HbA1c, WHR, albumin/creatinine ratio and HDL-cholesterol level. The discriminative ability of the model was adequate, with a concordance statistic (C-statistic) of 0.74. Discrimination was similar or even better in the independent cohorts, the C-statistics being: EDC, 0.79; FinnDiane, 0.82; and CACTI, 0.73.Our prognostic model, which uses easily accessible clinical features can discriminate between type 1 diabetes patients who have a good or a poor prognosis. Such a prognostic model may be helpful in clinical practice and for risk stratification in clinical trials.

    View details for DOI 10.1007/s00125-014-3358-x

    View details for Web of Science ID 000344630300007

    View details for PubMedID 25186291

    View details for PubMedCentralID PMC4399797

  • Cardiovascular Disease Risk Factors in Youth With Diabetes Mellitus A Scientific Statement From the American Heart Association CIRCULATION Maahs, D. M., Daniels, S. R., de Ferranti, S. D., Dichek, H. L., Flynn, J., Goldstein, B. I., Kelly, A. S., Nadeau, K. J., Martyn-Nemeth, P., Osganian, S. K., Quinn, L., Shah, A. S., Urbina, E. 2014; 130 (17): 1532-U224

    View details for DOI 10.1161/CIR.0000000000000094

    View details for Web of Science ID 000344064500019

    View details for PubMedID 25170098

  • Multicenter Closed-Loop/Hybrid Meal Bolus Insulin Delivery with Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Chase, H. P., Doyle, F. J., Zisser, H., Renard, E., Nimri, R., Cobelli, C., Buckingham, B. A., Maahs, D. M., Anderson, S., Magni, L., Lum, J., Calhoun, P., Kollman, C., Beck, R. W. 2014; 16 (10): 623-632

    Abstract

    This study evaluated meal bolus insulin delivery strategies and associated postprandial glucose control while using an artificial pancreas (AP) system.This study was a multicenter trial in 53 patients, 12-65 years of age, with type 1 diabetes for at least 1 year and use of continuous subcutaneous insulin infusion for at least 6 months. Four different insulin bolus strategies were assessed: standard bolus delivered with meal (n=51), standard bolus delivered 15 min prior to meal (n=40), over-bolus of 30% delivered with meal (n=40), and bolus purposely omitted (n=46). Meal carbohydrate (CHO) intake was 1 g of CHO/kg of body weight up to a maximum of 100 g for the first three strategies or up to a maximum of 50 g for strategy 4.Only three of 177 meals (two with over-bolus and one with standard bolus 15 min prior to meal) had postprandial blood glucose values of <60 mg/dL. Postprandial hyperglycemia (blood glucose level >180 mg/dL) was prolonged for all four bolus strategies but was shorter for the over-bolus (41% of the 4-h period) than the two standard bolus strategies (73% for each). Mean postprandial blood glucose level was 15.9 mg/dL higher for the standard bolus with meal compared with the prebolus (baseline-adjusted, P=0.07 for treatment effect over the 4-h period).The AP handled the four bolus situations safely, but at the expense of having elevated postprandial glucose levels in most subjects. This was most likely secondary to suboptimal performance of the algorithm.

    View details for DOI 10.1089/dia.2014.0050

    View details for Web of Science ID 000342561100003

    View details for PubMedID 25188375

    View details for PubMedCentralID PMC4183919

  • Serum uric acid predicts vascular complications in adults with type 1 diabetes: the coronary artery calcification in type 1 diabetes study ACTA DIABETOLOGICA Bjornstad, P., Maahs, D. M., Rivard, C. J., Pyle, L., Rewers, M., Johnson, R. J., Snell-Bergeon, J. K. 2014; 51 (5): 783-791

    Abstract

    Epidemiologic evidence supports a link between serum uric acid (SUA) and vascular complications in diabetes, but it remains unclear whether SUA improves the ability of conventional risk factor to predict complications. We hypothesized that SUA at baseline would independently predict the development of vascular complications over 6 years and that the addition of SUA to American Diabetes Association's ABC risk factors (HbA1c, BP, LDL-C) would improve vascular complication prediction over 6 years in adults with type 1 diabetes. Study participants (N = 652) were 19-56 year old at baseline and re-examined 6 years later. Diabetic nephropathy was defined as incident albuminuria or rapid GFR decline (>3.3 %/year) estimated by the CKD-EPI cystatin C. Diabetic retinopathy (DR) was based on self-reported history, and proliferative diabetic retinopathy (PDR) was defined as laser eye therapy; coronary artery calcium (CAC) was measured using electron-beam computed tomography. Progression of CAC (CACp) was defined as a change in the square-root-transformed CAC volume ≥2.5. Predictors of each complication were examined in stepwise logistic regression with subjects with complications at baseline excluded from analyses. C-statistics, integrated discrimination indices and net-reclassification improvement were utilized for prediction performance analyses. SUA independently predicted development of incident albuminuria (OR 1.8, 95 % CI 1.2-2.7), rapid GFR decline (1.9, 1.1-3.3), DR (1.4, 1.1-1.9), PDR (2.1, 1.4-3.0) and CACp (1.5, 1.1-1.9). SUA improved the discrimination and net-classification risk of vascular complications over 6 years. SUA independently predicted the development of vascular complications in type 1 diabetes and also improved the reclassification of vascular complications.

    View details for DOI 10.1007/s00592-014-0611-1

    View details for Web of Science ID 000342427800011

    View details for PubMedID 24929955

    View details for PubMedCentralID PMC4399796

  • FREQUENCY OF CONTINUOUS GLUCOSE MONITORING USE AND CHANGE IN HEMOGLOBIN A1C FOR ADULTS WITH TYPE 1 DIABETES IN A CLINICAL PRACTICE SETTING ENDOCRINE PRACTICE McQueen, R. B., Ellis, S. L., Maahs, D. M., Anderson, H. D., Nair, K. V., Campbell, J. D. 2014; 20 (10): 1007-1015

    Abstract

    To estimate the frequency of continuous glucose monitoring (CGM) use and change in hemoglobin A1c (HbA1c) compared to self-monitoring of blood glucose (SMBG) alone in adults with type 1 diabetes in a clinical practice setting.We retrospectively identified 66 adult type 1 diabetes patients at the Barbara Davis Center for Diabetes (BDC) who first initiated CGM between 2006 and 2011 and 67 controls using SMBG. The frequency of CGM use was estimated from survey recall and defined as the mean number of days/month of CGM use during a maximum follow-up of 10 months. Change in HbA1c was calculated as the difference between the baseline value and the lowest follow-up value.The mean change in HbA1c for CGM users was -0.48% (95% confidence interval [CI]: -0.67, -0.28) and for SMBG users was -0.37% (95% CI: -0.56, -0.18). The between-group mean difference in change in HbA1c, adjusted for patient characteristics, was -0.11% (95% CI: -0.38, 0.16), whereas the subgroup with a baseline HbA1c ≥7.0% and users of CGM ≥21 days/month was -0.36% (95% CI: -0.78, 0.05). Nearly half (n = 32, 48%) used CGM <21 days/month. The reasons for low frequency of CGM use or discontinuation included sensor costs, frequency of alarms, inaccuracy, and discomfort.These CGM data from clinical practice suggest a trend toward decreasing HbA1c for adults with type 1 diabetes, especially in patients with higher baseline HbA1c and higher frequency of CGM use. Future studies are needed to assess the use of CGM in larger populations of clinical practice adult type 1 diabetes patients.

    View details for DOI 10.4158/EP14027.OR

    View details for Web of Science ID 000350028200007

    View details for PubMedID 24793924

  • Real-Time Continuous Glucose Monitoring Among Participants in the T1D Exchange Clinic Registry DIABETES CARE Wong, J. C., Foster, N. C., Maahs, D. M., Raghinaru, D., Bergenstal, R. M., Ahmann, A. J., Peters, A. L., Bode, B. W., Aleppo, G., Hirsch, I. B., Kleis, L., Chase, H. P., DuBose, S. N., Miller, K. M., Beck, R. W., Adi, S. 2014; 37 (10): 2702-2709

    Abstract

    To assess the frequency of continuous glucose monitoring (CGM) device use, factors associated with its use, and the relationship of CGM with diabetes outcomes (HbA1c, severe hypoglycemia [SH], and diabetic ketoacidosis [DKA]).Survey questions related to CGM device use 1 year after enrollment in the T1D Exchange clinic registry were completed by 17,317 participants. Participants were defined as CGM users if they indicated using real-time CGM during the prior 30 days.Nine percent of participants used CGM (6% of children <13 years old, 4% of adolescents 13 to <18 years, 6% of young adults 18 to <26 years, and 21% of adults ≥26 years). CGM use was more likely with higher education, higher household income, private health insurance, longer duration of diabetes, and use of insulin pump (P < 0.01 all factors). CGM use was associated with lower HbA1c in children (8.3% vs. 8.6%, P < 0.001) and adults (7.7% vs. 7.9%, P < 0.001). In adults, more frequent use of CGM (≥6 days/week) was associated with lower mean HbA1c. Only 27% of users downloaded data from their device at least once per month, and ≤15% of users reported downloading their device at least weekly. Among participants who used CGM at baseline, 41% had discontinued within 1 year.CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently. Factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use.

    View details for DOI 10.2337/dc14-0303

    View details for Web of Science ID 000343582400022

    View details for PubMedID 25011947

    View details for PubMedCentralID PMC4392936

  • ISPAD Clinical Practice Consensus Guidelines 2014. Assessment and monitoring of glycemic control in children and adolescents with diabetes. Pediatric diabetes Rewers, M. J., Pillay, K., De Beaufort, C., Craig, M. E., Hanas, R., Acerini, C. L., Maahs, D. M. 2014; 15: 102-114

    View details for DOI 10.1111/pedi.12190

    View details for PubMedID 25182311

  • Introduction to ISPAD Clinical Practice Consensus Guidelines 2014 Compendium PEDIATRIC DIABETES Acerini, C., Craig, M. E., De Beaufort, C., Maahs, D. M., Hanas, R. 2014; 15: 1-3

    View details for DOI 10.1111/pedi.12182

    View details for Web of Science ID 000341716900001

    View details for PubMedID 25182304

  • Introduction to the limited care guidance appendix PEDIATRIC DIABETES Acerini, C. L., Craig, M. E., De Beaufort, C., Maahs, D. M., Pillay, K., Hanas, R. 2014; 15: 279-280

    View details for DOI 10.1111/pedi.12185

    View details for Web of Science ID 000341716900021

  • The delivery of ambulatory diabetes care to children and adolescents with diabetes PEDIATRIC DIABETES Pihoker, C., Forsander, G., Fantahun, B., Virmani, A., Luo, X., Hallman, M., Wolfsdorf, J., Maahs, D. M. 2014; 15: 86-101

    View details for DOI 10.1111/pedi.12181

    View details for Web of Science ID 000341716900008

  • A practical method to measure GFR in people with type 1 diabetes JOURNAL OF DIABETES AND ITS COMPLICATIONS Maahs, D. M., Bushman, L., Kerr, B., Ellis, S. L., Pyle, L., McFann, K., Bouffard, A., Bishop, F. K., Nguyen, N., Anderson, P. L. 2014; 28 (5): 667-673

    Abstract

    Improved early diagnostic methods are needed to identify risk for kidney disease in people with type 1 diabetes. We hypothesized that glomerular filtration rate (GFR) measured by iohexol clearance in dried blood spots (DBS) on filter paper would be comparable to plasma (gold-standard) and superior to estimated GFR (eGFR) and, second, that adjustment for ambient blood glucose would improve accuracy and precision of GFR measurement.GFR was measured by iohexol clearance in plasma, DBS, and as estimated by the CKD-Epidemiology Collaboration equations in 15 adults with type 1 diabetes at two visits, one euglycemic and one hyperglycemic.GFR measured by DBS was more comparable and less biased than GFR cystatin C, serum creatinine, and both combined. GFR was higher during hyperglycemia. Correction for between visit glycemia statistically significantly reduced bias and mean squared error for GFR measured by DBS as compared to gold-standard during euglycemia.Iohexol clearance measured with DBS performed better than eGFR methods. Correction for ambient blood glucose improved precision and accuracy of GFR measurement. This method is more convenient than the gold-standard GFR method and may improve screening and diagnostic capabilities in people with type 1 diabetes, especially when GFR is >60ml/min/1.73m(2).

    View details for DOI 10.1016/j.jdiacomp.2014.06.001

    View details for Web of Science ID 000341746800017

    View details for PubMedID 25027389

  • Assessment and monitoring of glycemic control in children and adolescents with diabetes PEDIATRIC DIABETES Rewers, M. J., Pillay, K., De Beaufort, C., Craig, M. E., Hanas, R., Acerini, C. L., Maahs, D. M. 2014; 15: 102-114

    View details for DOI 10.1111/pedi.12190

    View details for Web of Science ID 000341716900009

  • Assessment and management of hypoglycemia in children and adolescents with diabetes PEDIATRIC DIABETES Ly, T. T., Maahs, D. M., Rewers, A., Dunger, D., Oduwole, A., Jones, T. W. 2014; 15: 180-192

    View details for DOI 10.1111/pedi.12174

    View details for Web of Science ID 000341716900013

    View details for PubMedID 25040141

  • ISPAD Clinical Practice Consensus Guidelines 2014. Type 2 diabetes in the child and adolescent. Pediatric diabetes Zeitler, P., Fu, J., Tandon, N., Nadeau, K., Urakami, T., Barrett, T., Maahs, D. 2014; 15: 26-46

    View details for DOI 10.1111/pedi.12179

    View details for PubMedID 25182306

  • ISPAD Clinical Practice Consensus Guidelines 2014. Assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatric diabetes Ly, T. T., Maahs, D. M., Rewers, A., Dunger, D., Oduwole, A., Jones, T. W. 2014; 15: 180-192

    View details for DOI 10.1111/pedi.12174

    View details for PubMedID 25040141

  • ISPAD Clinical Practice Consensus Guidelines 2014. The delivery of ambulatory diabetes care to children and adolescents with diabetes. Pediatric diabetes Pihoker, C., Forsander, G., Fantahun, B., Virmani, A., Luo, X., Hallman, M., Wolfsdorf, J., Maahs, D. M. 2014; 15: 86-101

    View details for DOI 10.1111/pedi.12181

    View details for PubMedID 25182310

  • Type 2 diabetes in the child and adolescent PEDIATRIC DIABETES Zeitler, P., Fu, J., Tandon, N., Nadeau, K., Urakami, T., Barrett, T., Maahs, D. 2014; 15: 26-46

    View details for DOI 10.1111/pedi.12179

    View details for Web of Science ID 000341716900004

  • Contrasting the clinical care and outcomes of 2,622 children with type 1 diabetes less than 6 years of age in the United States T1D Exchange and German/Austrian DPV registries DIABETOLOGIA Maahs, D. M., Hermann, J. M., DuBose, S. N., Miller, K. M., Heidtmann, B., Dimeglio, L. A., Rami-Merhar, B., Beck, R. W., Schober, E., Tamborlane, W. V., Kapellen, T. M., Holl, R. W. 2014; 57 (8): 1578-1585

    Abstract

    The study aimed to compare participant characteristics, treatment modalities and clinical outcomes in registry participants less than 6 years old.Participant characteristics, treatment modalities and clinical outcomes (HbA1c, severe hypoglycaemia [SH] and diabetic ketoacidosis [DKA]) as well as frequencies of attaining HbA1c goals in line with the International Society for Pediatric and Adolescent Diabetes (<7.5% [<58 mmol/mol]) and ADA (<8.5% [<69 mmol/mol]) were compared.Insulin pump use was more frequent (74% vs 50%, p < 0.001) and HbA1c levels lower in the Prospective Diabetes Follow-up Registry (DPV) than in the T1D Exchange (T1DX) (mean 7.4% vs 8.2%, p < 0.001). A lower HbA1c level was seen in the DPV compared with the T1DX for both pump users (p < 0.001) and injection users (p < 0.001). More children from DPV were meeting the recommended HbA1c goals, compared with children from T1DX (HbA1c <7.5%: 56% vs 22%, p < 0.001; HbA1c <8.5%: 90% vs 66%, p < 0.001). The adjusted odds of having an HbA1c level <7.5% or <8.5% were 4.2 (p < 0.001) and 3.6 (p < 0.001) higher for the DPV than the T1DX, respectively. The frequency of SH did not differ between registries or by HbA1c, whereas the frequency of DKA was higher for the T1DX and greater in those with higher HbA1c levels.DPV data indicate that an HbA1c of <7.5% can frequently be achieved in children with type 1 diabetes who are under 6 years old. An improved metabolic control of type 1 diabetes in young patients appears to decrease the risk of DKA without increasing SH. The greater frequency of suboptimal control in young patients in the T1DX compared with the DPV is not fully explained by a less frequent use of insulin pumps and may relate to the higher HbA1c targets that are recommended for this age group in the USA.

    View details for DOI 10.1007/s00125-014-3272-2

    View details for Web of Science ID 000338997500008

    View details for PubMedID 24893863

  • Early diabetic nephropathy in type 1 diabetes: new insights CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY Bjornstad, P., Cherney, D., Maahs, D. M. 2014; 21 (4): 279-286

    Abstract

    Despite improvements in glycemic and blood pressure control in patients with type 1 diabetes, diabetic nephropathy remains the most common cause of chronic kidney disease worldwide. A major challenge in preventing diabetic nephropathy is the inability to identify high-risk patients at an early stage, emphasizing the importance of discovering new therapeutic targets and implementation of clinical trials to reduce diabetic nephropathy risk.Limitations of managing patients with diabetic nephropathy with renin-angiotensin-aldosterone system blockade have been identified in recent clinical trials, including the failure of primary prevention studies in T1D and the demonstration of harm with dual renin-angiotensin-aldosterone system blockade. Fortunately, several new targets, including serum uric acid, insulin sensitivity, vasopressin, and sodium-glucose cotransporter-2 inhibition, are promising in the prevention and treatment of diabetic nephropathy.Diabetic nephropathy is characterized by a long clinically silent period without signs or symptoms of disease. There is an urgent need for improved methods of detecting early mediators of renal injury, to ultimately prevent the initiation and progression of diabetic nephropathy. In this review, we will focus on early diabetic nephropathy and summarize potential new therapeutic targets.

    View details for DOI 10.1097/MED.0000000000000074

    View details for Web of Science ID 000338130600005

    View details for PubMedID 24983394

    View details for PubMedCentralID PMC4138314

  • Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy NEPHROLOGY DIALYSIS TRANSPLANTATION Siwy, J., Schanstra, J. P., Argiles, A., Bakker, S. J., Beige, J., Boucek, P., Brand, K., Delles, C., Duranton, F., Fernandez-Fernandez, B., Jankowski, M., Al Khatib, M., Kunt, T., Lajer, M., Lichtinghagen, R., Lindhardt, M., Maahs, D. M., Mischak, H., Mullen, W., Navis, G., Noutsou, M., Ortiz, A., Persson, F., Petrie, J. R., Roob, J. M., Rossing, P., Ruggenenti, P., Rychlik, I., Serra, A. L., Snell-Bergeon, J., Spasovski, G., Stojceva-Taneva, O., Trillini, M., von der Leyen, H., Winklhofer-Roob, B. M., Zuerbig, P., Jankowski, J. 2014; 29 (8): 1563-1570

    Abstract

    Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273).In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier.We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found.We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.

    View details for DOI 10.1093/ndt/gfu039

    View details for Web of Science ID 000339948100019

    View details for PubMedID 24589724

    View details for PubMedCentralID PMC4118140

  • A Randomized Trial of a Home System to Reduce Nocturnal Hypoglycemia in Type 1 Diabetes DIABETES CARE Maahs, D. M., Calhoun, P., Buckingham, B. A., Chase, H. P., Hramiak, I., Lum, J., Cameron, F., Bequette, B. W., Aye, T., Paul, T., Slover, R., Wadwa, R. P., Wilson, D. M., Kollman, C., Beck, R. W. 2014; 37 (7): 1885-1891

    Abstract

    Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels.Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred.Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm.Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis.

    View details for DOI 10.2337/dc13-2159

    View details for Web of Science ID 000338020400022

    View details for PubMedCentralID PMC4067393

  • A randomized trial of a home system to reduce nocturnal hypoglycemia in type 1 diabetes. Diabetes care Maahs, D. M., Calhoun, P., Buckingham, B. A., Chase, H. P., Hramiak, I., Lum, J., Cameron, F., Bequette, B. W., Aye, T., Paul, T., Slover, R., Wadwa, R. P., Wilson, D. M., Kollman, C., Beck, R. W. 2014; 37 (7): 1885-1891

    Abstract

    Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels.Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred.Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm.Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis.

    View details for DOI 10.2337/dc13-2159

    View details for PubMedID 24804697

    View details for PubMedCentralID PMC4067393

  • Depression in Adults in the T1D Exchange Clinic Registry DIABETES CARE Trief, P. M., Xing, D., Foster, N. C., Maahs, D. M., Kittelsrud, J. M., Olson, B. A., Young, L. A., Peters, A. L., Bergenstal, R. M., Miller, K. M., Beck, R. W., Weinstock, R. S. 2014; 37 (6): 1563-1572

    Abstract

    Little is known about the frequency of depression in adults with type 1 diabetes (T1D) or its relationship to diabetes outcomes. The T1D Exchange clinic registry allowed us to explore depression in a large, heterogeneous sample.Participants ≥18 years old (N = 6,172; median age 34 years; median diabetes duration 16 years; 55% female; and 89% non-Hispanic white) completed the eight-item Patient Health Questionnaire (PHQ-8), a validated, reliable measure of current depression. Probable major depression was defined in four ways: PHQ-8 ≥10, PHQ-8 ≥12, per diagnostic algorithm, and as a continuous variable. Characteristics and clinical outcomes of those with and without depression were compared using logistic and linear regression models.A total of 4.6-10.3% of participants were classified as probable major depression depending on how defined. Participants classified as depressed were more likely female, nonwhite race/ethnicity, to have a lower household income and lower education level, to exercise less often, to miss insulin doses, and to have one or more complications (neuropathy, nephropathy, treatment for retinopathy, or cardiovascular/cerebrovascular disease) (all P < 0.01). HbA1c was higher in the depressed versus not depressed groups (8.4 ± 1.7% [68 ± 8.6 mmol/mol] vs. 7.8 ± 1.4% [62 ± 15.3 mmol/mol]; P < 0.001). Occurrence of one or more diabetic ketoacidosis events (11 vs. 4%; P < 0.001) and one or more severe hypoglycemic events (18 vs. 9%; P < 0.001) in the past 3 months was higher among depressed participants.In the T1D Exchange clinic registry, adults with probable major depression have worse clinical outcomes than those not depressed. Whether identification and treatment of depression improves diabetes outcomes requires study. Depression is common in T1D, and better identification and treatment of this comorbid condition is needed.

    View details for DOI 10.2337/dc13-1867

    View details for Web of Science ID 000337746100030

    View details for PubMedID 24855157

  • Association Between Glycated Hemoglobin and Health Utility for Type 1 Diabetes PATIENT-PATIENT CENTERED OUTCOMES RESEARCH McQueen, R. B., Ellis, S. L., Maahs, D. M., Anderson, H. D., Nair, K. V., Libby, A. M., Campbell, J. D. 2014; 7 (2): 197-205

    Abstract

    Cost-effectiveness models for diabetes link glycated hemoglobin (HbA1c) to diabetes-related complications. Independent of diabetes-related complications, there is little known on the association between HbA1c and health utility scores. This link can alter the cost effectiveness of interventions designed to improve HbA1c. The cross-sectional relationship between HbA1c and health utility scores in adult type 1 diabetes patients was estimated after adjusting for diabetes-related complications.The EuroQoL-5 dimension (EQ-5D) questionnaire and an ad hoc survey requesting demographic information and adherence to glucose monitoring therapies was administered to adult type 1 diabetes patients during a clinic visit and combined with clinical medical record data. Health utility scores were derived using the US time-tradeoff valuation of the EQ-5D. Linear regression was used to estimate the relationship between HbA1c and utility, adjusting for treatments, demographics, and diabetes-related complications.Among 176 patients, mean (standard deviation [SD]) age was 38 (12.2) years, duration of disease was 22 (12.1) years, and number of chronic conditions other than type 1 diabetes was 2.7 (2.0). Unadjusted mean (SD) utility was 0.94 (0.09) for those with HbA1c levels <7 % (n = 54), 0.89 (0.15) for those with HbA1c ≥ 7 % (n = 122), and 0.91 (0.14) for all patients. After adjustment, a 1 % absolute increase in HbA1c was associated with a disutility of -0.03 (95 % confidence interval [CI] -0.049, -0.006).Findings suggest that, after adjusting for diabetes-related complications, higher HbA1c levels are associated with a significant health disutility. Pending additional data from longitudinal studies, these findings could be used in cost-effectiveness evaluations of type 1 diabetes interventions that impact HbA1c.

    View details for DOI 10.1007/s40271-014-0045-4

    View details for Web of Science ID 000344366900008

    View details for PubMedID 24458545

  • Frequency of Morning Ketosis After Overnight Insulin Suspension Using an Automated Nocturnal Predictive Low Glucose Suspend System DIABETES CARE Beck, R. W., Raghinaru, D., Wadwa, R. P., Chase, H. P., Maahs, D. M., Buckingham, B. A. 2014; 37 (5): 1224-1229

    Abstract

    To assess the effect of overnight insulin pump suspension in an automated predictive low glucose suspend system on morning blood glucose and ketone levels in an attempt to determine whether routine measurement of ketone levels is useful when a closed-loop system that suspends insulin delivery overnight is being used.Data from an in-home randomized trial of 45 individuals with type 1 diabetes (age range 15-45 years) were analyzed, evaluating an automated predictive low glucose pump suspension system in which blood glucose, blood ketone, and urine ketone levels were measured on 1,954 mornings.One or more pump suspensions occurred during 744 of the 977 intervention nights (76%). The morning blood ketone level was ≥0.6 mmol/L after 11 of the 744 nights (1.5%) during which a pump suspension occurred and 2 of the 233 nights (0.9%) during which there was no suspension compared with 11 of 977 control nights (1.1%). The morning blood ketone level was ≥0.6 mmol/L after only 2 of 159 nights (1.3%) with a pump suspension exceeding 2 h. Morning fasting blood glucose level was not a good predictor of the presence of blood ketones.Routine measurement of blood or urine ketones during use of an automated pump suspension system using continuous glucose monitoring, whether threshold based or predictive, is not necessary. Recommendations for checking ketone levels should be no different when a patient is using a system with automated insulin suspension than it is for conventional diabetes self-management.

    View details for DOI 10.2337/dc13-2775

    View details for Web of Science ID 000334840100034

    View details for PubMedID 24757229

    View details for PubMedCentralID PMC3994933

  • The Effects of Lowering Nighttime and Breakfast Glucose Levels with Sensor-Augmented Pump Therapy on Hemoglobin A1c Levels in Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Chase, H. P., Westfall, E., Slover, R., Huang, S., Shin, J. J., Kaufman, F. R., Pyle, L., Snell-Bergeon, J. K. 2014; 16 (5): 284-291

    Abstract

    This study determined the association of continuous glucose monitoring glucose (CGM-glucose) levels at different times of the day with improvement in glycated hemoglobin (HbA1c) levels. The potential application of these data is to focus effort to improve glucose control in patients with type 1 diabetes.Data were analyzed from 196 patients with type 1 diabetes who were randomized to receive sensor-augmented pump therapy in the 1-year STAR 3 trial. CGM-glucose values and HbA1c levels from baseline and after 1 year were evaluated to determine associations of improvement in CGM-glucose at different times of the day with longitudinal improvement in HbA1c.Improvement in HbA1c levels after 1 year was related to improvement in mean CGM-glucose levels in daytime (6 a.m.-midnight), overnight (midnight-6 a.m.), and each mealtime period (P<0.0001 for each). In multivariable analysis, only improvement in breakfast meal period was associated with improvement in HbA1c after 1 year, explaining 59% of the HbA1c improvement using the partial R(2) test. Moreover, among those patients who only improved CGM-glucose in the overnight period there was an associated improvement in breakfast meal period CGM-glucose of 26 ± 22 mg/dL (P<0.01).Breakfast period glucose improvement had the greatest effect on lowering HbA1c levels in patients with type 1 diabetes. Improving glucose control overnight resulted in subsequent improvement in the breakfast period. Although glucose control should be improved at all times, methods to improve overnight and post-breakfast glucose levels may be of primary importance in improving glucose control in patients with type 1 diabetes.

    View details for DOI 10.1089/dia.2013.0227

    View details for Web of Science ID 000336894100003

    View details for PubMedID 24450776

  • Update: Ambulatory Blood Pressure Monitoring in Children and Adolescents A Scientific Statement From the American Heart Association HYPERTENSION Flynn, J. T., Daniels, S. R., Hayman, L. L., Maahs, D. M., McCrindle, B. W., Mitsnefes, M., Zachariah, J. P., Urbina, E. M. 2014; 63 (5): 1116-1135

    View details for DOI 10.1161/HYP.0000000000000007

    View details for Web of Science ID 000334320900044

    View details for PubMedID 24591341

    View details for PubMedCentralID PMC4146525

  • Serum uric acid and insulin sensitivity in adolescents and adults with and without type 1 diabetes JOURNAL OF DIABETES AND ITS COMPLICATIONS Bjornstad, P., Snell-Bergeon, J. K., McFann, K., Wadwa, R. P., Rewers, M., Rivard, C. J., Jalal, D., Chonchol, M. B., Johnson, R. J., Maahs, D. M. 2014; 28 (3): 298-304

    Abstract

    Decreased insulin sensitivity (IS) exists in type 1 diabetes. Serum uric acid (SUA), whose concentration is related to renal clearance, predicts vascular complications in type 1 diabetes. SUA is also inversely associated with IS in non-diabetics, but has not been examined in type 1 diabetes. We hypothesized SUA would be associated with reduced IS in adolescents and adults with type 1 diabetes.The cross-sectional and longitudinal associations of SUA with IS were investigated in 254 adolescents with type 1 diabetes and 70 without in the Determinants of Macrovascular Disease in Adolescents with Type 1 Diabetes Study, and in 471 adults with type 1 diabetes and 571 without in the Coronary Artery Calcification in Type 1 diabetes (CACTI) study.SUA was lower in subjects with type 1 diabetes (p<0.0001), but still remained inversely associated with IS after multivariable adjustments in adolescents (β±SE: -1.99±0.62, p=0.001, R2 =2%) and adults (β±SE: -0.91±0.33, p=0.006, R2 = 6%) with type 1 diabetes, though less strongly than in non-diabetic controls (adolescents: β±SE: -2.70±1.19, p=0.03, R2 = 15%, adults: β±SE: -5.99±0.75, p<0.0001, R2 =39%).We demonstrated a significantly weaker relationship between SUA and reduced IS in subjects with type 1 diabetes than non-diabetic controls.

    View details for DOI 10.1016/j.jdiacomp.2013.12.007

    View details for Web of Science ID 000335717800010

    View details for PubMedID 24461546

    View details for PubMedCentralID PMC4004676

  • Fasting Blood Glucose-A Missing Variable for GFR-Estimation in Type 1 Diabetes? PLOS ONE Bjornstad, P., McQueen, R. B., Snell-Bergeon, J. K., Cherney, D., Pyle, L., Perkins, B., Rewers, M., Maahs, D. M. 2014; 9 (4)

    Abstract

    Estimation of glomerular filtration rate (eGFR) is one of the current clinical methods for identifying risk for diabetic nephropathy in subjects with type 1 diabetes (T1D). Hyperglycemia is known to influence GFR in T1D and variability in blood glucose at the time of eGFR measurement could introduce bias in eGFR. We hypothesized that simultaneously measured blood glucose would influence eGFR in adults with T1D.Longitudinal multivariable mixed-models were employed to investigate the relationships between blood glucose and eGFR by CKD-EPI eGFRCYSTATIN C over 6-years in the Coronary Artery Calcification in Type 1 diabetes (CACTI) study. All subjects with T1D and complete data including blood glucose and cystatin C for at least one of the three visits (n = 616, 554, and 521, respectively) were included in the longitudinal analyses.In mixed-models adjusting for sex, HbA1c, ACEi/ARB, protein and sodium intake positive associations were observed between simultaneous blood glucose and eGFRCYSTATIN C (β±SE:0.14±0.04 per 10 mg/dL of blood glucose, p<0.0001), and hyperfiltration as a dichotomous outcome (OR: 1.04, 95% CI: 1.01-1.07 per 10 mg/dL of blood glucose, p = 0.02).In our longitudinal data in subjects with T1D, simultaneous blood glucose has an independent positive effect on eGFRCYSTATIN C. The associations between blood glucose and eGFRCYSTATIN C may bias the accurate detection of early diabetic nephropathy, especially in people with longitudinal variability in blood glucose.

    View details for DOI 10.1371/journal.pone.0096264

    View details for Web of Science ID 000335504900027

    View details for PubMedID 24781861

    View details for PubMedCentralID PMC4004575

  • Serum Uric Acid and Hypertension in Adults: A Paradoxical Relationship in Type 1 Diabetes JOURNAL OF CLINICAL HYPERTENSION Bjornstad, P., Wadwa, R. P., Sirota, J. C., Snell-Bergeon, J. K., McFann, K., Rewers, M., Rivard, C. J., Jalal, D., Chonchol, M. B., Johnson, R. J., Maahs, D. M. 2014; 16 (4): 283-288

    Abstract

    Adults with type 1 diabetes have lower serum uric acid levels compared with nondiabetic adults. Little is known about the relationship between serum uric acid and blood pressure in type 1 diabetes and whether it differs from the positive relationship found in nondiabetic adults. The authors assessed the cross-sectional and longitudinal relationships over 6 years between serum uric acid and blood pressure in adults with (35±9 years [n=393]) and without (38±9 years [n=685]) type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study. In nondiabetic adults, serum uric acid was associated with systolic blood pressure in multivariable models adjusted for cardiovascular risk factors. In adults with type 1 diabetes, a negative association was observed between serum uric acid and systolic blood pressure after multivariable adjustments. A positive association was observed between serum uric acid and systolic blood pressure in nondiabetic adults. In contrast, an inverse relationship was demonstrated after multivariable adjustments in type 1 diabetes.

    View details for DOI 10.1111/jch.12305

    View details for Web of Science ID 000334290700014

    View details for PubMedID 24667019

    View details for PubMedCentralID PMC3989383

  • Ideal Cardiovascular Health and the Prevalence and Progression of Coronary Artery Calcification in Adults With and Without Type 1 Diabetes DIABETES CARE Alman, A. C., Maahs, D. M., Rewers, M. J., Snell-Bergeon, J. K. 2014; 37 (2): 521-528

    Abstract

    In 2010, the American Heart Association defined seven metrics (smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting plasma glucose) for ideal cardiovascular health (ICH). Subsequent studies have shown that the prevalence of achieving these metrics is very low in the general population. Adults with type 1 diabetes are at increased risk of cardiovascular disease (CVD), but no studies to date have been published on the prevalence of ICH in this population.Data for this analysis were collected as part of the prospective Coronary Artery Calcification in Type 1 Diabetes study. This analysis involved 546 subjects with type 1 diabetes and 631 subjects without diabetes who had complete information for calculating the ICH metrics.Overall, the prevalence of ICH was low in this population, with none meeting the ideal criteria for all seven metrics. The prevalence of ideal physical activity (10.0%) and diet (1.1%) were particularly low. ICH was significantly associated with both decreased prevalence (odds ratio [OR] 0.70; 95% CI 0.62-0.80) and progression (OR 0.77; 95% CI 0.66-0.90) of coronary artery calcification (CAC).ICH is significantly associated with decreased prevalence and progression of CAC; however, prevalence of ICH metrics was low in adults both with and without type 1 diabetes. Efforts to increase the prevalence of ICH could have a significant impact on reducing the burden of CVD.

    View details for DOI 10.2337/dc13-0997

    View details for Web of Science ID 000331072800043

    View details for PubMedID 24130360

    View details for PubMedCentralID PMC3898750

  • Changes in diet and physical activity in adolescents with and without type 1 diabetes over time. International journal of pediatric endocrinology Bishop, F. K., Wadwa, R. P., Snell-Bergeon, J., Nguyen, N., Maahs, D. M. 2014; 2014 (1): 17-?

    Abstract

    Diet and physical activity (PA) are fundamental aspects of care in type 1 diabetes, but scant longitudinal data exist on these behaviors in adolescents with type 1 diabetes, especially compared to non-diabetic controls.Data in 211 adolescents with type 1 diabetes (baseline age = 15.3 ± 2.2 years, diabetes duration = 8.8 ± 3.1 years, A1c = 9.0 ± 1.5%, 51% male) and 67 non-diabetic (age = 14.9 ± 1.7 years, 52% male) controls were collected at baseline (V1) and again at 2-year follow-up (V2) (mean follow up = 2.2 ± 0.4 years). Diet data (meals/day, snacks/day, and weekly consumption of breakfast, fruit, vegetables and fried foods), and PA were collected using interviewer administered questionnaires. T-tests and chi-squared tests were used for comparisons.Both adolescents with type 1 diabetes and non-diabetic controls reported increased vegetable (2.8 v. 3.6 and 3.1 v. 3.8 times weekly, respectively, p < 0.0001) and fruit (2.9 v. 3.8, both groups, p < 0.0001) intake (times per week) and increased PA (hours/day; 1.8 v. 2.2, p = 0.005 and 1.5 v. 1.9, p = 0.008, respectively) from V1 to V2. Adolescents with type 1 diabetes reported eating breakfast (3.3 v. 3.8 weekly, p = 0.0002) but also fried foods (1.9 v. 2.3, p = 0.0005) weekly more often from V1 to V2. Adolescents with and without type 1 diabetes met PA recommendations of 60 minutes or more of moderate-to-hard PA daily at both V1 (74% v. 70%, respectively, p = 0.58) and V2 (70% v. 78%, respectively, p = 0.78).Over 2 years, adolescents with and without type 1 diabetes had a healthier diet with increased fruit and vegetable intake and increased PA. However, neither group met the guidelines of daily breakfast, fruit and vegetable intake. Some diet and PA improvements were seen in adolescents with type 1 diabetes over a 2-year period. Therefore, adolescence could be a beneficial time to target diet and lifestyle interventions to take advantage of this time period when behaviors are being modified.

    View details for DOI 10.1186/1687-9856-2014-17

    View details for PubMedID 25191342

    View details for PubMedCentralID PMC4154618

  • The effect of insurance status and parental education on glycemic control and cardiovascular disease risk profile in youth with Type 1 Diabetes. Journal of diabetes and metabolic disorders Majidi, S., Wadwa, R. P., Bishop, F. K., Klingensmith, G. J., Rewers, M., McFann, K., Maahs, D. M. 2014; 13: 59-?

    Abstract

    Adult studies have shown a correlation between low socioeconomic status and Type 1 Diabetes complications, but studies have not been done in children to examine the effect of socioeconomic status on risk for future complications. This study investigates the relationship between insurance status and parental education and both glycemic control and cardiovascular disease (CVD) risk factors in youth with type 1 diabetes.A cross-sectional study of 295 youth with established type 1 diabetes who underwent examination with fasting blood draw and reported insurance status and parental education.Youth with type 1 diabetes and public insurance had higher hemoglobin A1c (HbA1c), body mass index, hs-CRP, and blood pressure (p < 0.05) than those with private insurance. Insulin regimen varied between insurance groups, and differences in HbA1c and CVD risk factors, except for diastolic blood pressure (DBP), were no longer evident after controlling for insulin regimen. Parental education was not associated with HbA1c or CVD risk factors.Youth with type 1 diabetes and public insurance have worse glycemic control and elevated CVD risk factors compared to those with private insurance, but this was no longer seen when insulin regimen was controlled for. Further research is needed to look at differences between those with public insurance and private insurance that contribute to differences in type 1 diabetes outcomes, and to identify modifiable risk factors in pediatric patients in order to focus earlier interventions to decrease and prevent future diabetes complications.

    View details for DOI 10.1186/2251-6581-13-59

    View details for PubMedID 24955334

    View details for PubMedCentralID PMC4064822

  • Early Diabetic Nephropathy A complication of reduced insulin sensitivity in type 1 diabetes DIABETES CARE Bjornstad, P., Snell-Bergeon, J. K., Rewers, M., Jalal, D., Chonchol, M. B., Johnson, R. J., Maahs, D. M. 2013; 36 (11): 3678-3683

    Abstract

    Diabetic nephropathy (DN) is a major cause of mortality in type 1 diabetes. Reduced insulin sensitivity is a well-documented component of type 1 diabetes. We hypothesized that baseline insulin sensitivity would predict development of DN over 6 years.We assessed the relationship between insulin sensitivity at baseline and development of early phenotypes of DN-microalbuminuria (albumin-creatinine ratio [ACR] ≥30 mg/g) and rapid renal function decline (glomerular filtration rate [GFR] loss >3 mL/min/1.73 m2 per year)-with three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations over 6 years. Subjects with diabetes (n = 449) and without diabetes (n = 565) in the Coronary Artery Calcification in Type 1 Diabetes study had an estimated insulin sensitivity index (ISI) at baseline and 6-year follow-up.The ISI was lower in subjects with diabetes than in those without diabetes (P < 0.0001). A higher ISI at baseline predicted a lower odds of developing an ACR ≥30 mg/g (odds ratio 0.65 [95% CI 0.49-0.85], P = 0.003) univariately and after adjusting for HbA1c (0.69 [0.51-0.93], P = 0.01). A higher ISI at baseline conferred protection from a rapid decline of GFR as assessed by CKD-EPI cystatin C (0.77 [0.64-0.92], P = 0.004) and remained significant after adjusting for HbA1c and age (0.80 [0.67-0.97], P = 0.02). We found no relation between ISI and rapid GFR decline estimated by CKD-EPI creatinine (P = 0.38) or CKD-EPI combined cystatin C and creatinine (P = 0.50).Over 6 years, a higher ISI independently predicts a lower odds of developing microalbuminuria and rapid GFR decline as estimated with cystatin C, suggesting a relationship between insulin sensitivity and early phenotypes of DN.

    View details for DOI 10.2337/dc13-0631

    View details for Web of Science ID 000326274100052

    View details for PubMedID 24026551

    View details for PubMedCentralID PMC3816872

  • Correlates of Medical Nutrition Therapy and Cardiovascular Outcomes in Youth With Type 1 Diabetes JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR The, N. S., Crandell, J. L., Thomas, J., Couch, S. C., Shah, A. S., Maahs, D. M., Dabelea, D., Marcovina, S. M., D'Agostino, R. B., Mayer-Davis, E. J. 2013; 45 (6): 661-668

    Abstract

    To examine whether the types of medical nutrition therapies (MNTs) taught to and used by youth with type 1 diabetes (T1D) vary by sociodemographic characteristics and cardiovascular (CVD) risk factors.Cross-sectional study.The SEARCH for Diabetes in Youth study is a population-based cohort of individuals with clinical diagnosed diabetes.A total of 1,191 individuals with T1D.Types of MNTs and frequency of use.Bivariate analysis and multivariate linear regression (P < .05) RESULTS: More race/ethnic minorities (vs whites), individuals with parents with less than a high school education (vs high school or higher education), and overweight/obese (vs underweight/normal weight) were taught additional MNTs. For underweight/normal weight individuals exclusively taught carbohydrate counting, those who used this approach "often" had lower hemoglobin A1c (8.6% vs 8.9%) and triglycerides (73.5 vs 84.1 mg/dL) than those who used it "sometimes/never." "Often" use of additional MNTs beyond carbohydrate counting was not associated with better mean values for CVD risk factors.In individuals with T1D, race/ethnic minorities, individuals with parents with less than a high school education, and overweight/obese individuals are taught more MNTs. Further research is needed to understand the effectiveness of the various MNTs on CVD risk factors, and to identify how to translate nutrition knowledge to behavior and metabolic status.

    View details for DOI 10.1016/j.jneb.2013.06.003

    View details for Web of Science ID 000326596800024

    View details for PubMedID 23891147

    View details for PubMedCentralID PMC3825757

  • Albuminuria According to Status of Autoimmunity and Insulin Sensitivity Among Youth With Type 1 and Type 2 Diabetes DIABETES CARE Mottl, A. K., Lauer, A., Dabelea, D., Maahs, D. M., D'Agostino, R. B., Dolan, L. M., Gilliam, L. K., Lawrence, J. M., Rodriguez, B., Marcovina, S. M., Imperatore, G., Shankar, R. K., Afkarian, M., Reynolds, K., Liese, A. D., Mauer, M., Mayer-Davis, E. J. 2013; 36 (11): 3633-3638

    Abstract

    To evaluate whether etiologic diabetes type is associated with the degree of albuminuria in children with diabetes. RESEARCH DESIGN AND METHODS SEARCH: is an observational, longitudinal study of children with diabetes. Youth with newly diagnosed diabetes were classified according to diabetes autoantibody (DAA) status and presence of insulin resistance. We defined insulin resistance as an insulin sensitivity score <25th percentile for the United States general youth population. DAA status was based on positivity for the 65-kD isoform of glutamate decarboxylase and insulinoma-associated protein 2 antigens. The four etiologic diabetes type groups were as follows: DAA(+)/insulin-sensitive (IS) (n = 1,351); DAA(+)/insulin-resistant (IR) (n = 438); DAA(-)/IR (n = 379); and DAA(-)/IS (n = 233). Urinary albumin:creatinine ratio (UACR) was measured from a random urine specimen. Multivariable regression analyses assessed the independent relationship between the four diabetes type groups and magnitude of UACR.Adjusted UACR means across the four groups were as follows: DAA(+)/IS = 154 μg/mg; DAA(+)/IR = 137 μg/mg; DAA(-)/IR = 257 μg/mg; and DAA(-)/IS = 131 μg/mg (P < 0.005). Only DAA(-)/IR was significantly different. We performed post hoc multivariable regression analysis restricted to the two IR groups to explore the contribution of DAA status and insulin sensitivity (continuous) to the difference in UACR between the IR groups. Only insulin sensitivity was significantly associated with UACR (β = -0.54; P < 0.0001).In youth with diabetes, the DAA(-)/IR group had a greater UACR than all other groups, possibly because of the greater magnitude of insulin resistance. Further exploration of the relationships between severity of insulin resistance, autoimmunity, and albuminuria in youth with diabetes is warranted.

    View details for DOI 10.2337/dc13-0568

    View details for Web of Science ID 000326274100045

    View details for PubMedID 23846811

    View details for PubMedCentralID PMC3816857

  • The Association between Vitamin D and Vascular Stiffness in Adolescents with and without Type 1 Diabetes PLOS ONE Lieberman, R., Wadwa, R. P., Nhung Nguyen, N., Bishop, F. K., Reinick, C., Snell-Bergeon, J. K., Maahs, D. M. 2013; 8 (10)
  • Factors Associated With Microalbuminuria in 7,549 Children and Adolescents With Type 1 Diabetes in the T1D Exchange Clinic Registry DIABETES CARE Daniels, M., DuBose, S. N., Maahs, D. M., Beck, R. W., Fox, L. A., Gubitosi-Klug, R., Laffel, L. M., Miller, K. M., Speer, H., Tamborlane, W. V., Tansey, M. J. 2013; 36 (9): 2639-2645

    Abstract

    To examine factors associated with clinical microalbuminuria (MA) diagnosis in children and adolescents in the T1D Exchange clinic registry.T1D Exchange participants <20 years of age with type 1 diabetes ≥ 1 year and urinary albumin-to-creatinine ratio (ACR) measured within the prior 2 years were included in the analysis. MA diagnosis required all of the following: 1) a clinical diagnosis of sustained MA or macroalbuminuria, 2) confirmation of MA diagnosis by either the most recent ACR being ≥ 30 mg/g or current treatment with an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB), and 3) no known cause for nephropathy other than diabetes. Logistic regression was used to assess factors associated with MA.MA was present in 329 of 7,549 (4.4%) participants, with a higher frequency associated with longer diabetes duration, higher mean glycosylated hemoglobin (HbA1c) level, older age, female sex, higher diastolic blood pressure (BP), and lower BMI (P ≤ 0.01 for each in multivariate analysis). Older age was most strongly associated with MA among participants with HbA1c ≥ 9.5% (≥ 80 mmol/mol). MA was uncommon (<2%) among participants with HbA1c <7.5% (<58 mmol/mol). Of those with MA, only 36% were receiving ACEI/ARB treatment.Our results emphasize the importance of good glycemic and BP control, particularly as diabetes duration increases, in order to reduce the risk of nephropathy. Since age and diabetes duration are important nonmodifiable factors associated with MA, the importance of routine screening is underscored to ensure early diagnosis and timely treatment of MA.

    View details for DOI 10.2337/dc12-2192

    View details for Web of Science ID 000323420200051

    View details for PubMedID 23610082

    View details for PubMedCentralID PMC3747908

  • Impaired Renal Function Further Increases Odds of 6-Year Coronary Artery Calcification Progression in Adults With Type 1 Diabetes: The CACTI study DIABETES CARE Maahs, D. M., Jalal, D., Chonchol, M., Johnson, R. J., Rewers, M., Snell-Bergeon, J. K. 2013; 36 (9): 2607-2614

    Abstract

    To determine whether baseline estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) independently predict coronary artery calcification (CAC) progression, and to determine how eGFR changes over 6 years in adults with type 1 diabetes compared with nondiabetic adults.The Coronary Artery Calcification in Type 1 Diabetes study participants (n = 1,066) with complete data for eGFR assessment at baseline and 6 years were included. Three Chronic Kidney Disease Epidemiology Collaboration equations (serum creatinine, cystatin C, and both) were used to estimate eGFR. The association of baseline ACR and eGFR with CAC progression was analyzed using multiple logistic regression.Increasing categorical baseline ACR (<10, 10-30, and >30 µg/mg) predicted CAC progression in participants with type 1 diabetes (odds ratio [OR], 2.15; 95% CI, 1.50-3.09; 7.19 [3.90-13.26]; and 18.09 [8.48-38.62]), respectively, compared with nondiabetic subjects. Baseline eGFR <60 mL/min/1.73 m(2) also predicted CAC progression (OR, 5-7, compared with nondiabetic participants). ORs for CAC progression were higher in women than in men when using the cystatin C-based Chronic Kidney Disease Epidemiology Collaboration equations. Participants with type 1 diabetes had greater eGFR decreases over 6 years than nondiabetic participants using cystatin C-based equations.Although increasing ACR or decreasing eGFR predicts CAC progression, coronary atherosclerosis progresses faster in people with type 1 diabetes even in the absence of diabetic kidney disease. These findings emphasize the interaction between kidney disease and cardiovascular disease in type 1 diabetes and highlight the public health importance of lowering cardiorenal risk in people with type 1 diabetes.

    View details for DOI 10.2337/dc12-2538

    View details for Web of Science ID 000323420200047

    View details for PubMedID 23835686

    View details for PubMedCentralID PMC3747879

  • Outpatient Safety Assessment of an In-Home Predictive Low-Glucose Suspend System with Type 1 Diabetes Subjects at Elevated Risk of Nocturnal Hypoglycemia DIABETES TECHNOLOGY & THERAPEUTICS Buckingham, B. A., Cameron, F., Calhoun, P., Maahs, D. M., Wilson, D. M., Chase, H. P., Bequette, B. W., Lum, J., Sibayan, J., Beck, R. W., Kollman, C. 2013; 15 (8): 622-627

    Abstract

    Abstract Objective: Nocturnal hypoglycemia is a common problem with type 1 diabetes. In the home setting, we conducted a pilot study to evaluate the safety of a system consisting of an insulin pump and continuous glucose monitor communicating wirelessly with a bedside computer running an algorithm that temporarily suspends insulin delivery when hypoglycemia is predicted. Research Design and Methods: After the run-in phase, a 21-night randomized trial was conducted in which each night was randomly assigned 2:1 to have either the predictive low-glucose suspend (PLGS) system active (intervention night) or inactive (control night). Three predictive algorithm versions were studied sequentially during the study for a total of 252 intervention and 123 control nights. The trial included 19 participants 18-56 years old with type 1 diabetes (hemoglobin A1c level of 6.0-7.7%) who were current users of the MiniMed Paradigm(®) REAL-Time Revel™ System and Sof-sensor(®) glucose sensor (Medtronic Diabetes, Northridge, CA). Results: With the final algorithm, pump suspension occurred on 53% of 77 intervention nights. Mean morning glucose level was 144±48 mg/dL on the 77 intervention nights versus 133±57 mg/dL on the 37 control nights, with morning blood ketones >0.6 mmol/L following one intervention night. Overnight hypoglycemia was lower on intervention than control nights, with at least one value ≤70 mg/dL occurring on 16% versus 30% of nights, respectively, with the final algorithm. Conclusions: This study demonstrated that the PLGS system in the home setting is safe and feasible. The preliminary efficacy data appear promising with the final algorithm reducing nocturnal hypoglycemia by almost 50%.

    View details for DOI 10.1089/dia.2013.0040

    View details for Web of Science ID 000323203600003

    View details for PubMedID 23883408

  • Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study CURRENT DIABETES REPORTS Maahs, D. M., Caramori, L., Cherney, D. Z., Galecki, A. T., Gao, C., Jalal, D., Perkins, B. A., Pop-Busui, R., Rossing, P., Mauer, M., Doria, A. 2013; 13 (4): 550-559

    Abstract

    Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

    View details for DOI 10.1007/s11892-013-0381-0

    View details for Web of Science ID 000321517000011

    View details for PubMedID 23649945

    View details for PubMedCentralID PMC3703487

  • Severe Hypoglycemia and Diabetic Ketoacidosis in Adults With Type 1 Diabetes: Results From the T1D Exchange Clinic Registry JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Weinstock, R. S., Xing, D., Maahs, D. M., Michels, A., Rickels, M. R., Peters, A. L., Bergenstal, R. M., Harris, B., DuBose, S. N., Miller, K. M., Beck, R. W. 2013; 98 (8): 3411-3419

    Abstract

    Few studies have assessed factors associated with severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D).Our objective was to determine frequency of and factors associated with the occurrence of SH and DKA in adults with T1D.We conducted a cross-sectional analysis from the T1D Exchange clinic registry at 70 U.S. endocrinology centers.Analysis included 7012 participants in the T1D Exchange clinic registry aged 26 to 93 years old with T1D for ≥2 years.Higher frequencies of SH and DKA were associated with lower socioeconomic status (P < .001). SH was strongly associated with diabetes duration (P < .001), with 18.6% of those with diabetes ≥40 years having an event in the past 12 months. SH frequency was lowest in those with hemoglobin A1c (HbA1c) levels of 7.0% (53 mmol/mol) to 7.5% (58 mmol/mol), being higher in those with HbA1c levels <7.0% (<53 mmol/mol) or >7.5% (>58 mmol/mol). DKA frequency increased with higher HbA1c levels (P < .001), with 21.0% of those with HbA1c ≥10.0% (≥86 mmol/mol) having an event in the past 12 months.SH and DKA are more common in those with lower socioeconomic status. DKA, most common in those with HbA1c ≥10.0% (≥86 mmol/mol), should be largely preventable. In contrast, SH, most frequent with diabetes ≥40 years duration, cannot be abolished given the limitation of current therapies. To reduce SH in adults with longstanding diabetes, consideration should be given to modifying HbA1c goals, particularly in patients with very low HbA1c levels.

    View details for DOI 10.1210/jc.2013-1589

    View details for Web of Science ID 000322781300060

    View details for PubMedID 23760624

  • Renal Hyperfiltration and Systemic Blood Pressure in Patients with Uncomplicated Type 1 Diabetes Mellitus PLOS ONE Yang, G. K., Maahs, D. M., Perkins, B. A., Cherney, D. Z. 2013; 8 (7)

    Abstract

    Patients with type 1 diabetes mellitus (DM) and renal hyperfiltration also exhibit systemic microvascular abnormalities, including endothelial dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP) is less clear. We therefore measured BP, renal hemodynamic function and circulating renin angiotensin aldosterone system (RAAS) mediators in type 1 DM patients with hyperfiltration (n = 36, DM-H, GFR≥135 ml/min/1.73 m(2)) or normofiltration (n = 40, DM-N), and 56 healthy controls (HC). Since renal hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized that hyperfiltration would be associated with higher BP and elevated levels of circulating RAAS mediators.BP, glomerular filtration rate (GFR - inulin), effective renal plasma flow (paraaminohippurate) and circulating RAAS components were measured in DM-H, DM-N and HC during clamped euglycemia (4-6 mmol/L). Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9-11 mmol/L).Baseline GFR was elevated in DM-H vs. DM-N and HC (167±6 vs. 115±2 and 115±2 ml/min/1.73 m(2), p<0.0001). Baseline systolic BP (SBP, 117±2 vs. 111±2 vs. 109±1, p = 0.004) and heart rate (76±1 vs. 67±1 vs. 61±1, p<0.0001) were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM-H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42±5 vs. 86±14 vs. 276±41 ng/dl, p = 0.01). GFR (p<0.0001) and SBP (p<0.0001) increased during hyperglycemia in DM-N but not in DM-H.DM-H was associated with higher heart rate and SBP values and an exaggerated suppression of systemic aldosterone. Future work should focus on the mechanisms that explain this paradox in diabetes of renal hyperfiltration coupled with systemic RAAS suppression.

    View details for DOI 10.1371/journal.pone.0068908

    View details for Web of Science ID 000323350700107

    View details for PubMedID 23861950

    View details for PubMedCentralID PMC3701674

  • Most Youth With Type 1 Diabetes in the T1D Exchange Clinic Registry Do Not Meet American Diabetes Association or International Society for Pediatric and Adolescent Diabetes Clinical Guidelines DIABETES CARE Wood, J. R., Miller, K. M., Maahs, D. M., Beck, R. W., Dimeglio, L. A., Libman, I. M., Quinn, M., Tamborlane, W. V., Woerner, S. E. 2013; 36 (7): 2035-2037

    Abstract

    To assess the proportion of youth with type 1 diabetes under the care of pediatric endocrinologists in the United States meeting targets for HbA1c, blood pressure (BP), BMI, and lipids.Data were evaluated for 13,316 participants in the T1D Exchange clinic registry younger than 20 years old with type 1 diabetes for ≥1 year.American Diabetes Association HbA1c targets of <8.5% for those younger than 6 years, <8.0% for those 6 to younger than 13 years old, and <7.5% for those 13 to younger than 20 years old were met by 64, 43, and 21% of participants, respectively. The majority met targets for BP and lipids, and two-thirds met the BMI goal of <85th percentile.Most children with type 1 diabetes have HbA1c values above target levels. Achieving American Diabetes Association goals remains a significant challenge for the majority of youth in the T1D Exchange registry.

    View details for DOI 10.2337/dc12-1959

    View details for Web of Science ID 000321472700038

    View details for PubMedID 23340893

    View details for PubMedCentralID PMC3687259

  • Prospective Association Between Inflammatory Markers and Progression of Coronary Artery Calcification in Adults With and Without Type 1 Diabetes DIABETES CARE Alman, A. C., Kinney, G. L., Tracy, R. P., Maahs, D. M., Hoicanson, J. E., Rewers, M. J., Snell-Bergeon, J. K. 2013; 36 (7): 1967-1973

    Abstract

    The role of inflammation in the increased risk of cardiovascular disease in type 1 diabetes is unclear. We examined the association of inflammation and progression of coronary artery calcification (CAC)-a marker of subclinical atherosclerosis-in adults with and without type 1 diabetes.A nested case-control study was performed within the prospective cohort of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. Participants underwent two CAC measurements ~2.5 years apart. Case subjects (n = 204) were those with significant progression of CAC. Control subjects (n = 258) were frequency-matched to case subjects on diabetes status, sex, age, and baseline CAC status. Inflammatory marker assessments were performed on stored blood samples from baseline. A principal components analysis (PCA) was performed and a composite score derived from that analysis. The composite score was constructed by assigning a value of 1 for each PCA component where at least one of the markers exceeded the 75th percentile (range 0-4). Conditional logistic regression was used for the matching strategy.The first two components of the PCA were modestly (odds ratio 1.38 [95% CI 1.08-1.77] and 1.27 [1.02-1.59], respectively) associated with CAC progression after adjustment for other risk factors. The composite score was more strongly associated with CAC progression for those with elevated markers in three or four of the principal components compared with those with none.Measures of inflammation were associated with progression of CAC in a population of adults with and without type 1 diabetes.

    View details for DOI 10.2337/dc12-1874

    View details for Web of Science ID 000321472700028

    View details for PubMedID 23340891

    View details for PubMedCentralID PMC3687315

  • Physical activity, sedentary behaviors, physical fitness, and their relation to health outcomes in youth with type 1 and type 2 diabetes: A review of the epidemiologic literature JOURNAL OF SPORT AND HEALTH SCIENCE Liese, A. D., Ma, X., Maahs, D. M., Trilk, J. L. 2013; 2 (1): 21-38
  • BENEFITS OF ACCELEROMETER AND HEART RATE DATA FOR HYPOGLYCEMIA MITIGATION Cameron, F., Stenerson, M., Wilson, D. M., Maahs, D. M., Mayer-Davis, E. J., Bequette, B. W., Buckingham, B. A. MARY ANN LIEBERT INC. 2013: A93–A93
  • Estimated Insulin Sensitivity and Cardiovascular Disease Risk Factors in Adolescents with and without Type 1 Diabetes JOURNAL OF PEDIATRICS Specht, B. J., Wadwa, R. P., Snell-Bergeon, J. K., Nadeau, K. J., Bishop, F. K., Maahs, D. M. 2013; 162 (2): 297-301

    Abstract

    To test the hypothesis that cardiovascular disease (CVD) risk factors are similar in nondiabetic (non-DM) adolescents compared with those with type 1 diabetes (T1D) in the most insulin-sensitive (IS) tertile, and that CVD risk factors are more atherogenic with decreasing IS in adolescents with T1D.IS for adolescents with T1D (n = 292; age = 15.4 ± 2.1 years; duration = 8.8 ± 3.0 years, hemoglobin A1c = 8.9% ± 1.6%) and non-DM controls (n = 89; age = 15.4 ± 2.1 years) was estimated using the model: log(e)IS = .64725 - 0.02032 (waist [cm]) - 0.09779 (hemoglobin A1c [%]) - 0.00235 (triglycerides [mg/dL]). CVD risk factors (blood pressure, fasting total and low- and high-density lipoprotein-cholesterol (HDL-c), high sensitivity C-reactive protein, and body mass index z score) were compared between all non-DM adolescents and those with T1D in the most IS tertile, and then examined for a linear trend by IS tertile in adolescents with T1D, adjusted for sex, race/ethnicity, and Tanner stage.Estimated IS was significantly lower in adolescents with T1D compared with those without (T1D = 7.8 ± 2.4, non-DM = 11.5 ± 2.9; P < .0001). CVD risk factors were similar for non-DM compared with the adolescents with T1D with the most IS, except for higher (HDL-c) and diastolic blood pressure in adolescents with T1D (P < .05). Among adolescents with T1D, all CVD risk factors except for (HDL-c), were more atherogenic across decreasing IS tertiles in linear regression analysis (P < .05).Adolescents with T1D who are the most IS have similar CVD risk factors compared with non-DM adolescents. CVD risk factors are inversely associated with IS in adolescents with T1D. IS may be an important therapeutic target for reducing CVD risk factors in adolescents with T1D.

    View details for DOI 10.1016/j.jpeds.2012.07.036

    View details for Web of Science ID 000313579900017

    View details for PubMedID 22921593

    View details for PubMedCentralID PMC3509245

  • USING ACTIVITY MONITORS TO IMPROVE CGM SENSOR ANOMALY DETECTION BAYSAL, N., Cameron, F., Stenerson, M., Buckingham, B. A., Wilson, D. M., Mayer-Davis, E. J., Maahs, D. M., Bequette, B. W. MARY ANN LIEBERT INC. 2013: A2–A2
  • Lower A1c among adolescents with lower perceived A1c goal: a cross-sectional survey. International journal of pediatric endocrinology Clements, S. A., Anger, M. D., Bishop, F. K., McFann, K. K., Klingensmith, G. J., Maahs, D. M., Wadwa, R. P. 2013; 2013 (1): 17-?

    Abstract

    The International Society for Pediatric and Adolescent Diabetes (ISPAD) and the American Diabetes Association (ADA) have established a hemoglobin A1c (A1c) target of less than 7.5% for adolescents with type 1 diabetes (T1D). However, many adolescents are unaware of their A1c target, and little data exist on how knowledge of this A1c target affects the actual A1c they achieve. We sought to evaluate the relationship between awareness of the A1c target and the actual A1c achieved in adolescents with T1D.In a cohort of 240 adolescents with T1D age 13-19 years, we measured A1c and administered a questionnaire to assess their knowledge of the ISPAD guideline for A1c target.Of the total cohort, 42 subjects (18%) had an A1c below target and 198 subjects (82%) had an A1c above target. Almost all subjects (98%) reported that they were told their A1c target by a healthcare provider, and most of those (88%) claimed to know their A1c target, but few (8%) were correct. More subjects with actual A1c below 7.5% thought their A1c goal was lower than the ISPAD target, compared to subjects with A1c above target (75% vs. 59%, p = 0.07), although this did not achieve statistical significance.In this cohort of adolescents with T1D, there was a trend toward a lower achieved A1c in those with a lower perceived A1c goal. Further studies should focus on identification of factors influencing an adolescent's ability to achieve a lower A1c.

    View details for DOI 10.1186/1687-9856-2013-17

    View details for PubMedID 24156395

    View details for PubMedCentralID PMC4015741

  • The Importance of Palmitoleic Acid to Adipocyte Insulin Resistance and Whole-Body Insulin Sensitivity in Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Bergman, B. C., Howard, D., Schauer, I. E., Maahs, D. M., Snell-Bergeon, J. K., Clement, T. W., Eckel, R. H., Perreault, L., Rewers, M. 2013; 98 (1): E40-E50

    Abstract

    Type 1 diabetes is an insulin-resistant state, but it is less clear which tissues are affected. Our previous report implicated skeletal muscle and liver insulin resistance in people with type 1 diabetes, but this occurred independently of generalized, visceral, or ectopic fat.The aim of the study was to measure adipose tissue insulin sensitivity and plasma triglyceride composition in individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose.Fifty subjects (25 individuals with type 1 diabetes and 25 controls without) were studied. After 3 d of dietary control and overnight insulin infusion, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Infusions of [1,1,2,3,3-(2)H(2)]glycerol and [1-(13)C]palmitate were used to quantify lipid metabolism.Basal glycerol and palmitate rates of appearance were similar between groups, decreased more in control subjects during the first two stages of the clamp, and similarly suppressed during the highest insulin dose. The concentration of insulin required for 50% inhibition of lipolysis was twice as high in individuals with type 1 diabetes. Plasma triglyceride saturation was similar between groups, but palmitoleic acid in plasma triglyceride was inversely related to adipocyte insulin sensitivity. Unesterified palmitoleic acid in plasma was positively related to insulin sensitivity in controls, but not in individuals with type 1 diabetes.Adipose tissue insulin resistance is a significant feature of type 1 diabetes. Palmitoleic acid is not related to insulin sensitivity in type 1 diabetes, as it was in controls, suggesting a novel mechanism for insulin resistance in this population.

    View details for DOI 10.1210/jc.2012-2892

    View details for Web of Science ID 000316210300006

    View details for PubMedID 23150678

    View details for PubMedCentralID PMC3537110

  • Glucose Control Predicts 2-Year Change in Lipid Profile in Youth with Type 1 Diabetes JOURNAL OF PEDIATRICS Maahs, D. M., Dabelea, D., D'Agostino, R. B., Andrews, J. S., Shah, A. S., Crimmins, N., Mayer-Davis, E. J., Marcovina, S., Imperatore, G., Wadwa, R. P., Daniels, S. R., Reynolds, K., Hamman, R. F., Dolan, L. M. 2013; 162 (1): 101-U127

    Abstract

    To test the hypothesis that a change in glycated hemoglobin (A1c) over a follow-up interval of approximately 2 years would be associated with concomitant changes in fasting lipids in individuals with type 1 diabetes (T1D).All subjects with T1D diagnosed in 2002-2005 in the SEARCH for Diabetes in Youth study with at least 2 study visits ∼12 and ∼24 months after an initial visit were included (age at initial visit, 10.6 ± 4.1 years; 48% female; diabetes duration, 10 ± 7 months; 76% non-Hispanic white; A1c = 7.7% ± 1.4%). Longitudinal mixed models were fit to examine the relationship between change in A1c and change in lipid levels (total cholesterol [TC], high-density lipoprotein-cholesterol [HDL-c], low-density lipoprotein-cholesterol [LDL-c], log triglycerides [TG], and non-HDL-c) with adjustment for possible confounders.Change in A1c over time was significantly associated with changes in TC, HDL-c, LDL-c, TG, and non-HDL-c over the range of A1c values. For example, for a person with an A1c of 10% and then a 2% decrease in A1c 2 years later (to 8%), the model predicted concomitant changes in TC (-0.29 mmol/L, -11.4 mg/dL), HDL-c (0.03 mmol/L, 1.3 mg/dL), LDL-c (-0.23 mmol/L, -9.0 mg/dL), and non-HDL-c (-0.32 mmol/L, -12.4 mg/dL) and an 8.5% decrease in TG (mmol/L).Improved glucose control over a 2-year follow-up was associated with a more favorable lipid profile but may be insufficient to normalize lipids in dyslipidemic T1D youth needing to decrease lipids to goal.

    View details for DOI 10.1016/j.jpeds.2012.06.006

    View details for Web of Science ID 000312915900024

    View details for PubMedID 22795314

    View details for PubMedCentralID PMC3807690

  • The association between vitamin D and vascular stiffness in adolescents with and without type 1 diabetes. PloS one Lieberman, R., Wadwa, R. P., Nguyen, N., Bishop, F. K., Reinick, C., Snell-Bergeon, J. K., Maahs, D. M. 2013; 8 (10)

    Abstract

    Vitamin D deficiency is common and associated with increased cardiovascular disease (CVD) risk. Pulse wave velocity (PWV) is a marker of vascular stiffness associated with CVD. We hypothesized that Vitamin D (25 (OH) D) levels would be inversely associated with PWV in youth with and without type 1 diabetes (T1D).Comparisons were made between adolescents with T1D (n = 211; age = 17.5 ± 2.3 years; diabetes duration = 10.9 ± 3.2 years; A1c = 9.1 ± 1.7%) and non-DM controls (n = 67; age = 16.9 ± 1.9 years). PWV was measured in the carotid-femoral segment (Sphygmocor Vx, AtCor Medical, Lisle, IL).Vitamin D levels were similar in adolescents with T1D and controls (27.7 ± 0.7 v. 26.0 ± 1.3 ng/ml; p = 0.26). Vitamin D was significantly inversely associated with PWV after adjusting for age, sex, quarter of the year, and race-ethnicity in adolescents with T1D (beta = -0.01 ± 0.004, p = 0.02) but not in the non-DM adolescents (beta = -0.008 ± 0.008, p = 0.32). Vitamin D remained significantly associated with PWV after additionally adjusting for hs-CRP in adolescents with T1D (-0.01 ± 0.004, p = 0.01). After adjusting for BMI z-score, lipids, or blood pressure, the relationship of Vitamin D with PWV was not significant.Vitamin D levels were inversely associated with PWV in adolescents with T1D, but not independently of BMI, lipids, or blood pressure. Our data contrast with other reports and suggest further research is indicated to determine if Vitamin D supplementation would be beneficial to lower CVD risk in adolescents with T1D with vitamin D insufficiency or deficiency.

    View details for DOI 10.1371/journal.pone.0077272

    View details for PubMedID 24204786

    View details for PubMedCentralID PMC3812200

  • Randomized Nutrition Education Intervention to Improve Carbohydrate Counting in Adolescents with Type 1 Diabetes Study: Is More Intensive Education Needed? JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS Spiegel, G., Bortsov, A., Bishop, F. K., Owen, D., Klingensmith, G. J., Mayer-Davis, E. J., Maahs, D. M. 2012; 112 (11): 1736-1746

    Abstract

    Youth with type 1 diabetes do not count carbohydrates accurately, yet it is an important strategy in blood glucose control.The study objective was to determine whether a nutrition education intervention would improve carbohydrate counting accuracy and glycemic control.We conducted a randomized, controlled nutrition intervention trial that was recruited from February 2009 to February 2010.Youth (12 to 18 years of age, n = 101) with type 1 diabetes were screened to identify those with poor carbohydrate counting accuracy, using a previously developed carbohydrate counting accuracy test covering commonly consumed foods and beverage items presented in six mixed meals and two snacks. All participants (n = 66, age = 15 ± 3 years, 41 male, diabetes duration = 6 ± 4 years, hemoglobin A1c [HbA1c] = 8.3% ± 1.1%) were randomized to the control or intervention group at the baseline visit. The intervention group attended a 90-minute class with a registered dietitian/certified diabetes educator and twice kept 3-day food records, which were used to review carbohydrate counting progress.Carbohydrate counting accuracy (measured as described) and HbA1c were evaluated at baseline and 3 months to determine the effectiveness of the intervention.t Tests, Spearman correlations, and repeated measures models were used.At baseline, carbohydrate content was over- and underestimated in 16 and 5 of 29 food items, respectively. When foods were presented as mixed meals, participants either significantly over- or underestimated 10 of the 9 meals and 4 snacks. After 3 months of follow-up, HbA1c decreased in both the intervention and control groups by -0.19% ± 0.12% (P = 0.12) and -0.08% ± 0.11% (P = 0.51), respectively; however, the overall intervention effect was not statistically significant for change in HbA1c or carbohydrate counting accuracy.More intensive intervention might be required to improve adolescents' carbohydrate counting accuracy and nutrition management of type 1 diabetes. Additional research is needed to translate nutrition education into improved health outcomes.

    View details for DOI 10.1016/j.jand.2012.06.001

    View details for Web of Science ID 000310819200006

    View details for PubMedID 22975086

    View details for PubMedCentralID PMC3487717

  • Implementation of proteomic biomarkers: making it work EUROPEAN JOURNAL OF CLINICAL INVESTIGATION Mischak, H., Ioannidis, J. P., Argiles, A., Attwood, T. K., Bongcam-Rudloff, E., Broenstrup, M., Charonis, A., Chrousos, G. P., Delles, C., Dominiczak, A., Dylag, T., Ehrich, J., Egido, J., Findeisen, P., Jankowski, J., Johnson, R. W., Julien, B. A., Lankisch, T., Leung, H. Y., Maahs, D., Magni, F., Manns, M. P., Manolis, E., Mayer, G., Navis, G., Novak, J., Ortiz, A., Persson, F., Peter, K., Riese, H. H., Rossing, P., Sattar, N., Spasovski, G., Thongboonkerd, V., Vanholder, R., Schanstra, J. P., Vlahou, A. 2012; 42 (9): 1027-1036

    Abstract

    While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare.

    View details for DOI 10.1111/j.1365-2362.2012.02674.x

    View details for Web of Science ID 000307473300014

    View details for PubMedID 22519700

    View details for PubMedCentralID PMC3464367

  • Inpatient studies of a Kalman-filter-based predictive pump shutoff algorithm. Journal of diabetes science and technology Cameron, F., Wilson, D. M., Buckingham, B. A., Arzumanyan, H., Clinton, P., Chase, H. P., Lum, J., Maahs, D. M., Calhoun, P. M., Bequette, B. W. 2012; 6 (5): 1142-1147

    Abstract

    An insulin pump shutoff system can prevent nocturnal hypoglycemia and is a first step on the pathway toward a closed-loop artificial pancreas. In previous pump shutoff studies using a voting algorithm and a 1 min continuous glucose monitor (CGM), 80% of induced hypoglycemic events were prevented.The pump shutoff algorithm used in previous studies was revised to a single Kalman filter to reduce complexity, incorporate CGMs with different sample times, handle sensor signal dropouts, and enforce safety constraints on the allowable pump shutoff time.Retrospective testing of the new algorithm on previous clinical data sets indicated that, for the four cases where the previous algorithm failed (minimum reference glucose less than 60 mg/dl), the mean suspension start time was 30 min earlier than the previous algorithm. Inpatient studies of the new algorithm have been conducted on 16 subjects. The algorithm prevented hypoglycemia in 73% of subjects. Suspension-induced hyperglycemia is not assessed, because this study forced excessive basal insulin infusion rates.The new algorithm functioned well and is flexible enough to handle variable sensor sample times and sensor dropouts. It also provides a framework for handling sensor signal attenuations, which can be challenging, particularly when they occur overnight.

    View details for PubMedID 23063041

    View details for PubMedCentralID PMC3570849

  • Outpatient Assessment of Determinants of Glucose Excursions in Adolescents with Type 1 Diabetes: Proof of Concept DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Mayer-Davis, E., Bishop, F. K., Wang, L., Mangan, M., McMurray, R. G. 2012; 14 (8): 658-664

    Abstract

    Abstract Objective: Controlled inpatient studies on the effects of food, physical activity (PA), and insulin dosing on glucose excursions exist, but such outpatient data are limited. We report here outpatient data on glucose excursions and its key determinants over 5 days in 30 adolescents with type 1 diabetes (T1D) as a proof-of-principle pilot study.Subjects (20 on insulin pumps, 10 receiving multiple daily injections; 15±2 years old; diabetes duration, 8±4 years; hemoglobin A1c, 8.1±1.0%) wore a continuous glucose monitor (CGM) and an accelerometer for 5 days. Subjects continued their existing insulin regimens, and time-stamped insulin dosing data were obtained from insulin pump downloads or insulin pen digital logs. Time-stamped cell phone photographs of food pre- and post-consumption and food logs were used to augment 24-h dietary recalls for Days 1 and 3. These variables were incorporated into regression models to predict glucose excursions at 1-4 h post-breakfast.CGM data on both Days 1 and 3 were obtained in 57 of the possible 60 subject-days with an average of 125 daily CGM readings (out of a possible 144). PA and dietary recall data were obtained in 100% and 93% of subjects on Day 1 and 90% and 100% of subjects on Day 3, respectively. All of these variables influenced glucose excursions at 1-4 h after waking, and 56 of the 60 subject-days contributed to the modeling analysis.Outpatient high-resolution time-stamped data on the main inputs of glucose variability in adolescents with T1D are feasible and can be modeled. Future applications include using these data for in silico modeling and for monitoring outpatient iterations of closed-loop studies, as well as to improve clinical advice regarding insulin dosing to match diet and PA behaviors.

    View details for DOI 10.1089/dia.2012.0053

    View details for Web of Science ID 000307125800004

    View details for PubMedID 22853720

    View details for PubMedCentralID PMC3409451

  • Early Detection of Kidney Disease in Type 1 Diabetes: What Do We Really Know? DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M. 2012; 14 (7): 541-544

    View details for DOI 10.1089/dia.2012.0089

    View details for Web of Science ID 000306245600001

    View details for PubMedID 22540522

  • Cardiovascular Disease (CVD) Limbo: How Soon and Low Should We Go to Prevent CVD in Diabetes? DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M. 2012; 14 (6): 449-452

    View details for DOI 10.1089/dia.2012.0078

    View details for Web of Science ID 000304788400001

    View details for PubMedID 22472062

  • Current Knowledge and Future Directions on Cardiovascular Disease in Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Snell-Bergeon, J. K. 2012; 14: S75-S76

    View details for DOI 10.1089/dia.2012.0106

    View details for Web of Science ID 000304752300010

    View details for PubMedID 22650228

    View details for PubMedCentralID PMC4971415

  • Cardiovascular Disease in Children and Adolescents with Diabetes: Where Are We, and Where Are We Going? DIABETES TECHNOLOGY & THERAPEUTICS Truong, U. T., Maahs, D. M., Daniels, S. R. 2012; 14: S11-S21

    Abstract

    The increasing prevalence of type 1 and type 2 diabetes mellitus combined with advancement in early detection of cardiovascular disease (CVD) has placed CVD as a significant concern for preventative pediatric medicine. The public health burden of type 2 diabetes is predicted to parallel increasing obesity in children with a projected increase of early CVD in adulthood. In this article, we review practice guidelines for cardiovascular health in children and adolescents with diabetes and data on which they are based. We then focus on imaging modalities that are promising tools to expand our understanding of the cardiovascular risk imposed on youths with diabetes.

    View details for DOI 10.1089/dia.2012.0018

    View details for Web of Science ID 000304752300003

    View details for PubMedID 22650220

    View details for PubMedCentralID PMC4239674

  • Features of Hepatic and Skeletal Muscle Insulin Resistance Unique to Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Bergman, B. C., Howard, D., Schauer, I. E., Maahs, D. M., Snell-Bergeon, J. K., Eckel, R. H., Perreault, L., Rewers, M. 2012; 97 (5): 1663-1672

    Abstract

    Type 1 diabetes is known to be a state of insulin resistance; however, the tissues involved in whole-body insulin resistance are less well known. It is unclear whether insulin resistance is due to glucose toxicity in the post-Diabetes Control and Complications Trial era of tighter glucose control.We performed this study to determine muscle and liver insulin sensitivity individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose concentration.Fifty subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes duration 22.9 ± 1.7 yr, without known end organ damage] were frequency matched on age and body mass index by group and studied. After 3 d of dietary control and overnight insulin infusion to normalize glucose, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Glucose metabolism was quantified using an infusion of [6,6-(2)H(2)]glucose. Hepatic insulin sensitivity was measured using the insulin IC(50) for glucose rate of appearance (Ra), whereas muscle insulin sensitivity was measured using the glucose rate of disappearance during the highest insulin dose.Throughout the study, glucose Ra was significantly greater in individuals compared with those without type 1 diabetes. The concentration of insulin required for 50% suppression of glucose Ra was 2-fold higher in subjects with type 1 diabetes. Glucose rate of disappearance was significantly lower in individuals with type 1 diabetes during the 8- and 40-mU/m(2) · min stages.Insulin resistance in liver and skeletal muscle was a significant feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was not explained by body mass index, percentage fat, plasma lipids, visceral fat, and physical activity and was also not fully explained by hyperglycemia.

    View details for DOI 10.1210/jc.2011-3172

    View details for Web of Science ID 000303915900059

    View details for PubMedID 22362823

    View details for PubMedCentralID PMC3339891

  • Adiponectin Dysregulation and Insulin Resistance in Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Pereira, R. I., Snell-Bergeon, J. K., Erickson, C., Schauer, I. E., Bergman, B. C., Rewers, M., Maahs, D. M. 2012; 97 (4): E642-E647

    Abstract

    Type 1 diabetes (T1D) is associated with insulin resistance despite elevated levels of the insulin-sensitizing protein adiponectin. Whether the expected positive correlation between adiponectin and insulin sensitivity is preserved in a T1D population is unknown.We measured the correlation between total and high-molecular-weight (HMW) adiponectin and insulin sensitivity in T1D patients and nondiabetic controls and identified determinants of adiponectin levels in patients with T1D.Fasting total and HMW adiponectin were measured in 86 subjects from the Coronary Artery Calcification in T1D (CACTI) cohort (39 T1D, 47 nondiabetic; age 45 ± 8 yr; 55% female). The association of adiponectin levels with insulin sensitivity was analyzed.The study was conducted at an academic research institute.Fasting total and HMW adiponectin were measured by RIA and ELISA, respectively. Insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp. Multivariate linear regression was used to identify determinants of adiponectin levels.Adiponectin levels positively correlated with insulin sensitivity in both subject groups (total adiponectin, r = 0.33 P < 0.05 for T1D, r = 0.29 P < 0.05 controls), but insulin sensitivity was lower in T1D subjects at any given level of total or HMW adiponectin. Adiponectin levels were independently associated with age, gender, and trunk fat, but these variables did not account for increased adiponectin in patients with T1D.Adiponectin levels are positively correlated with insulin sensitivity in T1D patients. However, T1D patients have decreased insulin sensitivity compared with controls at every level of adiponectin, suggesting an important adaptive change of adiponectin set point.

    View details for DOI 10.1210/jc.2011-2542

    View details for Web of Science ID 000302787800019

    View details for PubMedID 22278421

    View details for PubMedCentralID PMC3319187

  • Novel Urinary Protein Biomarkers Predicting the Development of Microalbuminuria and Renal Function Decline in Type 1 Diabetes DIABETES CARE Schlatzer, D., Maahs, D. M., Chance, M. R., Dazard, J., Li, X., Hazlett, F., Rewers, M., Snell-Bergeon, J. K. 2012; 35 (3): 549-555

    Abstract

    To define a panel of novel protein biomarkers of renal disease.Adults with type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study who were initially free of renal complications (n = 465) were followed for development of micro- or macroalbuminuria (MA) and early renal function decline (ERFD, annual decline in estimated glomerular filtration rate of ≥3.3%). The label-free proteomic discovery phase was conducted in 13 patients who progressed to MA by the 6-year visit and 11 control subjects, and four proteins (Tamm-Horsfall glycoprotein, α-1 acid glycoprotein, clusterin, and progranulin) identified in the discovery phase were measured by enzyme-linked immunosorbent assay in 74 subjects: group A, normal renal function (n = 35); group B, ERFD without MA (n = 15); group C, MA without ERFD (n = 16); and group D, both ERFD and MA (n = 8).In the label-free analysis, a model of progression to MA was built using 252 peptides, yielding an area under the curve (AUC) of 84.7 ± 5.3%. In the validation study, ordinal logistic regression was used to predict development of ERFD, MA, or both. A panel including Tamm-Horsfall glycoprotein (odds ratio 2.9, 95% CI 1.3-6.2, P = 0.008), progranulin (1.9, 0.8-4.5, P = 0.16), clusterin (0.6, 0.3-1.1, P = 0.09), and α-1 acid glycoprotein (1.6, 0.7-3.7, P = 0.27) improved the AUC from 0.841 to 0.889.A panel of four novel protein biomarkers predicted early renal damage in type 1 diabetes. These findings require further validation in other populations for prediction of renal complications and treatment monitoring.

    View details for DOI 10.2337/dc11-1491

    View details for Web of Science ID 000300801400020

    View details for PubMedID 22238279

    View details for PubMedCentralID PMC3322681

  • Update on care of children with type 1 diabetes. Advances in pediatrics Majidi, S., Maahs, D. M. 2012; 59 (1): 303-327

    View details for DOI 10.1016/j.yapd.2012.04.007

    View details for PubMedID 22789584

  • Is Carbohydrate Counting Enough? Towards Perfection or Unwanted Complexity? DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Higgins, J. 2012; 14 (1): 3-5

    View details for DOI 10.1089/dia.2011.0234

    View details for Web of Science ID 000298816300002

    View details for PubMedID 22066526

  • Lessons learned from a lipid lowering trial in adolescents with type 1 diabetes. International journal of pediatric endocrinology Bishop, F. K., Wadwa, R. P., Ellis, S., Rewers, M., Maahs, D. M. 2012; 2012 (1): 24-?

    Abstract

    Herein, we describe recruitment efforts for a trial of lipid-lowering medications in adolescents with type 1 diabetes, age 12-21 years. Based on our experience, future studies will require multiple centers to enroll a sufficient number of participants for adequate data to direct dyslipidemia medication treatment guidelines for adolescents with type 1 diabetes.

    View details for DOI 10.1186/1687-9856-2012-24

    View details for PubMedID 22846167

    View details for PubMedCentralID PMC3476991

  • Sugar-sweetened and diet beverage consumption is associated with cardiovascular risk factor profile in youth with type 1 diabetes ACTA DIABETOLOGICA Bortsov, A. V., Liese, A. D., Bell, R. A., Dabelea, D., D'Agostino, R. B., Hamman, R. F., Klingensmith, G. J., Lawrence, J. M., Maahs, D. M., McKeown, R., Marcovina, S. M., Thomas, J., Williams, D. E., Mayer-Davis, E. J. 2011; 48 (4): 275-282

    Abstract

    The prevalence of cardiovascular disease (CVD) risk factors among youth with type 1 diabetes is high and associated with age, gender, and race/ethnicity. It has also been shown that youth with type 1 diabetes often do not follow dietary recommendations. The objective of this cross-sectional observational study was to explore the association of sugar-sweetened and diet beverage intake with A1c, plasma lipids, adiponectin, leptin, systolic, and diastolic blood pressure in youth with type 1 diabetes. We examined data from 1,806 youth age 10-22 years with type 1 diabetes, of which 22% were minority (10% Hispanic, 8% African Americans, 4% other races) and 48% were female. Sugar-sweetened beverage, diet beverage, and mineral water intake was assessed with a food frequency questionnaire. After adjustment for socio-demographic and clinical covariates, physical activity and total energy intake, high sugar-sweetened beverage intake (at least one serving per day vs. none), was associated with higher levels of total cholesterol, LDL cholesterol, and plasma triglycerides, but not with A1c. High diet beverage intake was associated with higher A1c, total cholesterol, LDL cholesterol, and triglycerides. These associations were partially confounded by body mass index, saturated fat and total fiber intake. High sugar-sweetened beverage intake may have an adverse effect on CVD risk in youth with type 1 diabetes. Diet beverage intake may be a marker of unhealthy lifestyle which, in turn, is associated with worse metabolic control and CVD risk profile in these youth. Youth with diabetes should be encouraged to minimize sugar-sweetened beverage intake.

    View details for DOI 10.1007/s00592-010-0246-9

    View details for Web of Science ID 000297515600002

    View details for PubMedID 21249401

    View details for PubMedCentralID PMC4669040

  • Age and Sex Influence Cystatin C in Adolescents With and Without Type 1 Diabetes DIABETES CARE Maahs, D. M., Prentice, N., McFann, K., Snell-Bergeon, J. K., Jalal, D., Bishop, F. K., Aragon, B., Wadwa, R. P. 2011; 34 (11): 2360-2362

    Abstract

    To compare serum cystatin C levels, a novel biomarker of renal function, in adolescents with and without type 1 diabetes and to determine what factors affect cystatin C levels.Cystatin C was measured in youth 12-19 years of age with (n = 259, diabetes duration 9 ± 3 years, HbA(1c) 8.9 ± 1.6%) and without diabetes (n = 78). Data were compared by diabetes status, and linear regression was used to determine factors affecting cystatin C.Cystatin C (0.698 ± 0.083 vs. 0.688 ± 0.127 mg/L, P = 0.40) was similar by diabetes status. In multiple linear regression, cystatin C was associated with age and serum creatinine in nondiabetic subjects and sex, age, and serum creatinine in subjects with diabetes (P < 0.05).These data suggest sex differences and age-related changes in cystatin C in adolescents with type 1 diabetes. An understanding of these changes is needed to determine the potential role of cystatin C as a marker of renal function in this population.

    View details for DOI 10.2337/dc11-0829

    View details for Web of Science ID 000296955100005

    View details for PubMedID 21926294

    View details for PubMedCentralID PMC3198267

  • Childhood obesity and cardiovascular disease: links and prevention strategies NATURE REVIEWS CARDIOLOGY Nadeau, K. J., Maahs, D. M., Daniels, S. R., Eckel, R. H. 2011; 8 (9): 513-525

    Abstract

    The prevalence and severity of pediatric obesity have dramatically increased since the late 1980s, raising concerns about a subsequent increase in cardiovascular outcomes. Strong evidence, particularly from autopsy studies, supports the concept that precursors of adult cardiovascular disease (CVD) begin in childhood, and that pediatric obesity has an important influence on overall CVD risk. Lifestyle patterns also begin early and impact CVD risk. In addition, obesity and other CVD risk factors tend to persist over time. However, whether childhood obesity causes adult CVD directly, or does so by persisting as adult obesity, or both, is less clear. Regardless, sufficient data exist to warrant early implementation of both obesity prevention and treatment in youth and adults. In this Review, we examine the evidence supporting the impact of childhood obesity on adult obesity, surrogate markers of CVD, components of the metabolic syndrome, and the development of CVD. We also evaluate how obesity treatment strategies can improve risk factors and, ultimately, adverse clinical outcomes.

    View details for DOI 10.1038/nrcardio.2011.86

    View details for Web of Science ID 000294202200005

    View details for PubMedID 21670745

    View details for PubMedCentralID PMC4292916

  • Uric Acid as a Mediator of Diabetic Nephropathy SEMINARS IN NEPHROLOGY Jalal, D. I., Maahs, D. M., Hovind, P., Nakagawa, T. 2011; 31 (5): 459-465

    Abstract

    Despite advances in the management of patients with diabetes, diabetic nephropathy (DN) remains the most common cause of end-stage renal disease in the United States and worldwide. Inflammation and endothelial dysfunction appear to play a central role in the onset and the progression of DN. Recent evidence has emerged in the past decade to suggest uric acid is an inflammatory factor and may play a role in endothelial dysfunction. This has lead our group and others to explore the role of uric acid in the onset and progression of DN. In this review, we highlight some of the animal and human studies that implicate uric acid in DN. Based on the evidence we review, we conclude the need for properly planned randomized controlled studies to decrease uric acid levels and assess the impact of such therapy on diabetic kidney disease.

    View details for DOI 10.1016/j.semnephrol.2011.08.011

    View details for Web of Science ID 000296486700011

    View details for PubMedID 22000654

    View details for PubMedCentralID PMC3197214

  • Prevention of Overweight/Obesity as a Strategy to Optimize Cardiovascular Health CIRCULATION Cornier, M., Marshall, J. A., Hill, J. O., Maahs, D. M., Eckel, R. H. 2011; 124 (7): 840-850
  • Systematic Shifts in Cystatin C Between 2006 and 2010 CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Maahs, D. M., Jalal, D., McFann, K., Rewers, M., Snell-Bergeon, J. K. 2011; 6 (8): 1952-1955

    Abstract

    Cystatin C is used increasingly as a biomarker of renal function; however, cystatin C assays are not standardized. Our objective was to compare cystatin C results within the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study over time and in repeated measures to evaluate for assay drift.Serum samples were obtained at baseline (visit 1 [V1], 2000 to 2002) and follow-up (visit 2 [V2], 2003 to 2005; visit 3 [V3], 2006 to 2008) and were assayed in 2006 (V1), 2007 to 2008 (V2), and 2010 (V3) in the same laboratory.Mean cystatin C levels measured using the Dade-Behring assay decreased over time in subjects, with measures at all three visits (V1: 0.80 ± 0.19 [0.42 to 3.41], V2: 0.75 ± 0.22 [0.39 to 3.77], and V3: 0.69 ± 0.22 [0.39 to 3.79]). Cystatin C values were lower in V1 and V2 samples remeasured in 2010 (mean differences -0.13 ± 0.04 and -0.08 ± 0.04, P < 0.0001 for both). Correlations for original and re-run values were strong for V1 (r = 0.99) and V2 (r = 0.99). Deming regression equations and Bland-Altman plots suggest a systematic shift in the values over time.Systematic shifts in cystatin C levels, which can be corrected by regression adjustment, occurred in our laboratory in samples measured in 2006 and 2007 to 2008 as compared with 2010. Assay standardization and measurement reliability for cystatin C must be addressed.

    View details for DOI 10.2215/CJN.11271210

    View details for Web of Science ID 000293721400023

    View details for PubMedID 21784814

    View details for PubMedCentralID PMC3156426

  • Lipoprotein-Associated Phospholipase A(2) Activity Predicts Progression of Subclinical Coronary Atherosclerosis DIABETES TECHNOLOGY & THERAPEUTICS Kinney, G. L., Snell-Bergeon, J. K., Maahs, D. M., Eckel, R. H., Ehrlich, J., Rewers, M., Hokanson, J. E. 2011; 13 (3): 381-387

    Abstract

    Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a lipoprotein-associated enzyme that cleaves oxidized phosphatidylcholines, generating pro-atherosclerotic lysophosphatidylcholine and oxidized free fatty acids. Lp-PLA₂ is independently associated with cardiovascular disease (CVD) in a variety of populations. Coronary calcium is a measure of subclinical CVD, and progression of coronary calcification predicts future CVD events. In type 1 diabetes there is an increase in coronary calcium and CVD despite a favorable lipid profile. Levels of Lp-PLA₂ in type 1 diabetes are not known, nor is the relationship between Lp-PLA₂ and progression of coronary calcification.The Coronary Artery Calcification in Type 1 Diabetes study measured coronary calcium by electron-beam computed tomography twice over a 2.6 ± 0.3-year interval. Lp-PLA₂ mass and activity were measured at baseline (n = 1,097 subjects, 506 with and 591 without type 1 diabetes).In type 1 diabetes Lp-PLA₂ mass was marginally higher (285 ± 79 vs. 278 ± 78 ng/mL, P = 0.1), and Lp-PLA₂ activity was significantly lower (137 ± 30 vs. 146 ± 36 nmol/min/mL, P < 0.0001) than in those without diabetes. There was a greater proportion of those with progression of coronary calcification in type 1 diabetes compared with those without diabetes (24% vs. 10%, P < 0.0001). Lp-PLA₂ activity was independently associated with progression of coronary calcification in multivariate analysis (4th quartile verses bottom three quartiles, odds ratio = 1.77 [1.08-2.91], P = 0.02). LpPLA₂ mass was not significantly associated with progression of coronary calcification in this cohort (P = 0.09).Lp-PLA₂ activity predicts progression of subclinical atherosclerosis in individuals with and without type 1 diabetes.

    View details for DOI 10.1089/dia.2010.0175

    View details for Web of Science ID 000287798200013

    View details for PubMedID 21291330

    View details for PubMedCentralID PMC3101921

  • Correlates of Dietary Intake in Youth with Diabetes: Results from the SEARCH for Diabetes in Youth Study JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR Bortsov, A., Liese, A. D., Bell, R. A., Dabelea, D., D'Agostino, R. B., Hamman, R. F., Klingensmith, G. J., Lawrence, J. M., Maahs, D. M., McKeown, R., Marcovina, S. M., Thomas, J., Mayer-Davis, E. J. 2011; 43 (2): 123-129

    Abstract

    To explore demographic, socioeconomic, diabetes-related, and behavioral correlates of dietary intake of dairy, fruit, vegetables, sweetened soda, fiber, calcium, and saturated fat in youth with diabetes.Cross-sectional study of youth 10-22 years old with type 1 (T1DM, n = 2,176) and type 2 diabetes (T2DM, n = 365). Association of dietary intake, demographics, socioeconomic status, behavioral, and diabetes-related measures was explored with quantile regression.T1DM males had lower consumption of vegetables, fruit, and fiber, and higher consumption of soda and saturated fat than females (P < .01). African Americans had lower dairy and higher soda intake than non-Hispanic T1DM whites (P < .01). Soda consumption was higher in older T2DM youth than in younger participants (P < .01). Lifestyle and physical activity patterns were also significantly associated with dietary intake.Identified demographic and behavioral correlates may help dietitians to focus on groups of youth with diabetes who have lower adherence to a healthful diet. Diet counseling groups may be tailored according to these major determinants.

    View details for DOI 10.1016/j.jneb.2009.12.007

    View details for Web of Science ID 000288307200009

    View details for PubMedID 21276755

    View details for PubMedCentralID PMC3055946

  • Association of insulin sensitivity to lipids across the lifespan in people with Type 1 diabetes DIABETIC MEDICINE Maahs, D. M., Nadeau, K., Snell-Bergeon, J. K., Schauer, I., Bergman, B., West, N. A., Rewers, M., Daniels, S. R., Ogden, L. G., Hamman, R. F., Dabelea, D. 2011; 28 (2): 148-155

    Abstract

    Insulin resistance and dyslipidaemia both increase cardiovascular risk in Type 1 diabetes. However, little data exist on the associations of insulin resistance to lipids in Type 1 diabetes. Our objective was to explore the associations between insulin resistance (assessed by glucose infusion rate) and lipids in people with Type 1 diabetes and determine whether adiposity and/or average glycaemia influence these associations.Hyperinsulinaemic-euglycaemic clamp studies were performed in 60 subjects with Type 1 diabetes aged 12-19 years (age 15±2 years, 57% female, duration of diabetes 6.3±3.8 years, HbA(1c) 8.6±1.5%, IFCC=70 mmol/mol) and 40 subjects with Type 1 diabetes aged 27-61 years (age 45±9 years, 53% female, duration of diabetes 23±8 years, HbA(1c) 7.5±0.9%, IFCC=58 mmol/mol). Multiple linear regression models were fit to examine the association between glucose infusion rate and fasting lipid levels with adjustment for possible confounders.Lower glucose infusion rate was significantly associated with lower levels of HDL cholesterol in youths with Type 1 diabetes and with higher levels of triglycerides and higher triglyceride/HDL ratio in both youths and adults. The magnitude of the associations between glucose infusion rate and lipid levels translate into interquartile differences of 0.098 mmol/l for HDL cholesterol, 0.17 mmol/l for triglycerides and 1.06 for triglycerides/HDL in the adolescents and 0.20 mmol/l for triglycerides and 1.01 for triglycerides/HDL in the adults. The associations were attenuated and no longer statistically significant by adjustment for adiposity among adults, while adjustment for HbA(1c) had a small effect in youths and adults.Lower insulin sensitivity is associated with a more atherogenic lipid profile in both youths and adults with Type 1 diabetes.

    View details for DOI 10.1111/j.1464-5491.2010.03143.x

    View details for Web of Science ID 000286107000004

    View details for PubMedID 21219421

    View details for PubMedCentralID PMC3395467

  • Development, validation and use of an insulin sensitivity score in youths with diabetes: the SEARCH for Diabetes in Youth study DIABETOLOGIA Dabelea, D., D'Agostino, R. B., Mason, C. C., West, N., Hamman, R. F., Mayer-Davis, E. J., Maahs, D., Klingensmith, G., Knowler, W. C., Nadeau, K. 2011; 54 (1): 78-86

    Abstract

    The ability to measure insulin sensitivity across the phenotypic spectrum of diabetes may contribute to a more accurate characterisation of diabetes type. Our goal was to develop and validate an insulin sensitivity (IS) score using the euglycaemic-hyperinsulinaemic clamp in a subset (n = 85) of 12- to 19-year-old youths with diabetes participating in the SEARCH study in Colorado, USA.Youths with a diagnosis of type 1 (n = 60) or type 2 diabetes (n = 25) underwent a 3 h clamp to measure glucose disposal rate (GDR, mg kg⁻¹ min⁻¹). Demographic (age, sex, race), clinical (BMI, waist, Tanner stage) and metabolic characteristics (HbA₁(c), lipids, blood pressure, urine albumin:creatinine) were used to estimate log(e)IS score via stepwise linear regression on a model-development set (n = 53). Estimated IS score was evaluated for reproducibility on two validation sets: youths with diabetes (n = 33) and healthy control youths (n = 22).The best model included waist, triacylglycerol (TG) and HbA₁(c) levels (R² = 0.74). Diabetes type did not enter the model and there were no significant interactions between diabetes type and other predictors. Estimated IS score correlated well (r = 0.65, p < 0.0001; r = 0.62, p = 0.002) with GDR on the two validation sets. Based on this analysis, we propose the following formula to estimate insulin sensitivity in youths with diabetes: [Formula: see text].Insulin sensitivity can be estimated in adolescents with diabetes using routinely collected measures. This score can be applied to epidemiological studies of youths with diabetes to characterise relationships between dimensions of diabetes type.

    View details for DOI 10.1007/s00125-010-1911-9

    View details for Web of Science ID 000284896900014

    View details for PubMedID 20886205

  • Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes The CACTI Study DIABETES Schauer, I. E., Snell-Bergeon, J. K., Bergman, B. C., Maahs, D. M., Kretowski, A., Eckel, R. H., Rewers, M. 2011; 60 (1): 306-314

    Abstract

    To assess insulin action on peripheral glucose utilization and nonesterified fatty acid (NEFA) suppression as a predictor of coronary artery calcification (CAC) in patients with type 1 diabetes and nondiabetic controls.Insulin action was measured by a three-stage hyperinsulinemic-euglycemic clamp (4, 8, and 40 mU/m²/min) in 87 subjects from the Coronary Artery Calcification in Type 1 Diabetes cohort (40 diabetic, 47 nondiabetic; mean age 45 ± 8 years; 55% female).Peripheral glucose utilization was lower in subjects with type 1 diabetes compared with nondiabetic controls: glucose infusion rate (mg/kg FFM/min) = 6.19 ± 0.72 vs. 12.71 ± 0.66, mean ± SE, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and final clamp glucose and insulin. Insulin-induced NEFA suppression was also lower in type 1 diabetic compared with nondiabetic subjects: NEFA levels (μM) during 8 mU/m²/min insulin infusion = 370 ± 27 vs. 185 ± 25, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and time point insulin. Lower glucose utilization and higher NEFA levels, correlated with CAC volume (r = -0.42, P < 0.0001 and r = 0.41, P < 0.0001, respectively) and predicted the presence of CAC (odds ratio [OR] = 0.45, 95% CI = 0.22-0.93, P = 0.03; OR = 2.4, 95% CI = 1.08-5.32, P = 0.032, respectively). Insulin resistance did not correlate with GHb or continuous glucose monitoring parameters.Type 1 diabetic patients are insulin resistant compared with nondiabetic subjects, and the degree of resistance is not related to current glycemic control. Insulin resistance predicts the extent of coronary artery calcification and may contribute to the increased risk of cardiovascular disease in patients with type 1 diabetes as well as subjects without diabetes.

    View details for DOI 10.2337/db10-0328

    View details for Web of Science ID 000286017300037

    View details for PubMedID 20978091

    View details for PubMedCentralID PMC3012187

  • Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease KIDNEY INTERNATIONAL Reed, B. Y., Masoumi, A., Elhassan, E., McFann, K., Cadnapaphornchai, M. A., Maahs, D. M., Snell-Bergeon, J. K., Schrier, R. W. 2011; 79 (1): 128-134

    Abstract

    Renal cysts, pain, and hematuria are common presentations of autosomal dominant polycystic kidney disease (ADPKD) in children. Renal function, however, is typically preserved in these patients despite increased renal volume. Since angiogenesis has been implicated in promotion of renal cyst growth in ADPKD, we measured the serum level of various angiogenic factors and early renal structural changes and cardiovascular parameters in 71 patients with ADPKD, with a mean age of 16 years. Renal structure and left ventricular mass index were measured by magnetic resonance imaging or by echocardiogram. Renal function was assessed by creatinine clearance and urinary protein excretion. Serum growth factor levels were measured by enzyme-linked immunosorbent assay. Because of skewed distributions, the various parameters are reported as log(10). Serum log(10) vascular endothelial growth factor was positively correlated with renal and cardiac structure, but negatively with creatinine clearance. Serum angiopoietin 1 levels significantly correlated with structural change in both the kidney and the heart and with urinary protein. Thus, the correlation between angiogenic growth factors with both renal and cardiac disease severity is compatible with a possible role for angiogenesis in the early progression of disease in ADPKD.

    View details for DOI 10.1038/ki.2010.355

    View details for Web of Science ID 000285334100015

    View details for PubMedID 20881939

    View details for PubMedCentralID PMC3815472

  • Report of the 36th ISPAD meeting, Buenos Aires, Argentina, 27-30 October 2010 PEDIATRIC DIABETES Benitez-Aguirre, P., Maahs, D. M. 2010; 11 (8): 583-591
  • Glycaemic variability is associated with coronary artery calcium in men with Type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes study DIABETIC MEDICINE Snell-Bergeon, J. K., Roman, R., Rodbard, D., Garg, S., Maahs, D. M., Schauer, I. E., Bergman, B. C., Kinney, G. L., Rewers, M. 2010; 27 (12): 1436-1442

    Abstract

    We investigated coronary artery calcium in association with glucose levels and variability measured using continuous glucose monitoring in adults with Type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study.Coronary artery calcium was measured by electron beam tomography. The presence of any coronary artery calcium was analysed with respect to glucose levels [mean(T) (mean glucose), % of values < 3.9 mmol/l, > 10 mmol/l and either < 3.9 or > 10 mmol/l] and glycaemic variability [sd(T) (sd of all glucose values); sd(dm) (sd of the daily mean glucose levels) and sd(hh:mm) (glucose sd for a specified time of day, over all days)] using 3-5 days of continuous glucose monitoring from 75 subjects (45 women, 30 men), age 42 ± 9 years (mean ± sd) and diabetes duration of 29 ± 8 years using logistic regression.We observed significant associations between coronary artery calcium and mean(T) (OR = 4.4, 95% CI 1.1-18.6), % of values > 10 mmol/l (OR = 5.5, 95% CI 1.3-22.6), % of measures < 3.9 or > 10 mmol/l (OR = 5.7, 95% CI 1.3-24.9), sd(T) (OR = 4.7, 95% CI 1.1-19.7), sd(dm) (OR = 6.0, 95% CI 1.2-30.4) and sd(hh:mm) (OR = 4.0, 95% CI 1.1-15.4), among men, but none of these variables were associated with the presence of coronary artery calcium in women.We report the novel finding that subclinical atherosclerosis is associated with glucose levels and variability in men with Type 1 diabetes. The relationship of coronary artery calcium and glucose variability in Type 1 diabetes, and potential gender differences in this association, deserve further study.

    View details for DOI 10.1111/j.1464-5491.2010.03127.x

    View details for Web of Science ID 000284070400014

    View details for PubMedID 21059097

    View details for PubMedCentralID PMC3052953

  • Association of glycaemia with lipids in adults with type 1 diabetes: modification by dyslipidaemia medication DIABETOLOGIA Maahs, D. M., Ogden, L. G., Dabelea, D., Snell-Bergeon, J. K., Daniels, S. R., Hamman, R. F., Rewers, M. 2010; 53 (12): 2518-2525

    Abstract

    Hyperglycaemia and dyslipidaemia are common metabolic abnormalities in adults with type 1 diabetes and both increase cardiovascular disease (CVD) risk. The hypothesis of this study was that change in HbA(1c) over 6 years would be associated with change in fasting lipids in adults with type 1 diabetes.The Coronary Artery Calcification in Type 1 Diabetes (CACTI) study examined 652 patients with type 1 diabetes (54% female); 559 and 543 had follow-up visits at 3 and 6 years. Baseline age (mean ± SD) was 37 ± 9 years, diabetes duration 23 ± 9 years, and HbA(1c) 8.0 ± 1.3%. Use of dyslipidaemia medication was 17%, 32%, and 46% at the three visits. Separate longitudinal mixed models were fitted to examine the relationship between change in HbA(1c) and change in fasting total cholesterol (TC), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), log triacylglycerols (TG), and non-HDL-cholesterol (non-HDL-c). Because of an interaction between dyslipidaemia medication use and association of HbA(1c) with lipids, results were stratified by dyslipidaemia medication use.Among patients not using dyslipidaemia medication, a higher HbA(1c) was associated with significantly worse levels of the lipids TC, LDL-c, TG and non-HDL-c (per 1% change in HbA1c, TC 0.101 mmol/l, 95% CI 0.050, 0.152; LDL-c 0.103 mmol/l, 95% CI 0.058, 0.148; TG 0.052 mmol/l, 95% CI 0.024, 0.081; and non-HDL-c 0.129 mmol/l, 95% CI 0.078, 0.180) but not HDL-c (-0.20 mmol/l, 95% CI -0.047, 0.007). The associations between HbA(1c) and any lipid outcome among those on dyslipidaemia medication were in the same direction, but attenuated compared with persons not on medication.Change in HbA(1c) is significantly associated with change in fasting lipids, but dyslipidaemia medications may be required to optimise lipid and cardiovascular health.

    View details for DOI 10.1007/s00125-010-1886-6

    View details for Web of Science ID 000284509900009

    View details for PubMedID 20820753

    View details for PubMedCentralID PMC3405233

  • Serum Uric Acid Predicts Progression of Subclinical Coronary Atherosclerosis in Individuals Without Renal Disease DIABETES CARE Rodrigues, T. C., Maahs, D. M., Johnson, R. J., Jalal, D. I., Kinney, G. L., Rivard, C., Rewers, M., Snell-Bergeon, J. K. 2010; 33 (11): 2471-2473

    Abstract

    To examine uric acid (UA) as a possible predictor of the progression of coronary artery calcification (CAC) using data from the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study.CAC was measured by electron beam tomography at the baseline and at a follow-up 6.0±0.5 years later. The study population included 443 participants with type 1 diabetes and 526 control subjects who were free of diagnosed coronary artery disease at baseline. The presence of renal disease was defined by the presence of albuminuria and/or low glomerular filtration rate.In subjects without renal disease, serum UA predicted CAC progression (odds ratio 1.30 [95% CI 1.07-1.58], P=0.007) independent of conventional cardiovascular risk factors including diabetes and the presence of metabolic syndrome.Serum UA levels predict the progression of coronary atherosclerosis and may be useful in identifying who is at risk for vascular disease in the absence of significant chronic kidney disease.

    View details for DOI 10.2337/dc10-1007

    View details for Web of Science ID 000284516400034

    View details for PubMedID 20798338

    View details for PubMedCentralID PMC2963516

  • Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals JOURNAL OF HYPERTENSION Delles, C., Schiffer, E., von zur Muhlen, C., Peter, K., Rossing, P., Parving, H., Dymott, J. A., Neisius, U., Zimmerli, L. U., Snell-Bergeon, J. K., Maahs, D. M., Schmieder, R. E., Mischak, H., Dominiczak, A. F. 2010; 28 (11): 2316-2322

    Abstract

    We studied the urinary proteome in a total of 623 individuals with and without coronary artery disease (CAD) in order to characterize multiple biomarkers that enable prediction of the presence of CAD.Urine samples were analyzed by capillary electrophoresis coupled online to micro time-of-flight mass spectrometry.We defined a pattern of 238 CAD-specific polypeptides from comparison of 586 spot urine samples from 408 individuals. This pattern identified patients with CAD in a blinded cohort of 138 urine samples (71 patients with CAD and 67 healthy individuals) with high sensitivity and specificity (area under the receiver operator characteristic curve 87%, 95% confidence interval 81-92) and was superior to previously developed 15-marker (area under the receiver operator characteristic curve 68%, P < 0.0001) and 17-marker panels (area under the receiver operator characteristic curve 77%, P < 0.0001). The sequences of the discriminatory polypeptides include fragments of alpha-1-antitrypsin, collagen types 1 and 3, granin-like neuroendocrine peptide precursor, membrane-associated progesterone receptor component 1, sodium/potassium-transporting ATPase gamma chain and fibrinogen-alpha chain. Several biomarkers changed significantly toward the healthy signature following 2-year treatment with irbesartan, whereas short-term treatment with irbesartan did not significantly affect the polypeptide pattern.Urinary proteomics identifies CAD with high confidence and might also be useful for monitoring the effects of therapeutic interventions.

    View details for DOI 10.1097/HJH.0b013e32833d81b7

    View details for Web of Science ID 000282987000020

    View details for PubMedID 20811296

  • Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to Pathophysiology PLOS ONE Maahs, D. M., Siwy, J., Argiles, A., Cerna, M., Delles, C., Dominiczak, A. F., Gayrard, N., Iphoefer, A., Jaensch, L., Jerums, G., Medek, K., Mischak, H., Navis, G. J., Roob, J. M., Rossing, K., Rossing, P., Rychlik, I., Schiffer, E., Schmieder, R. E., Wascher, T. C., Winklhofer-Roob, B. M., Zimmerli, L. U., Zuerbig, P., Snell-Bergeon, J. K. 2010; 5 (9)

    Abstract

    The pathogenesis of diabetes mellitus (DM) is variable, comprising different inflammatory and immune responses. Proteome analysis holds the promise of delivering insight into the pathophysiological changes associated with diabetes. Recently, we identified and validated urinary proteomics biomarkers for diabetes. Based on these initial findings, we aimed to further validate urinary proteomics biomarkers specific for diabetes in general, and particularity associated with either type 1 (T1D) or type 2 diabetes (T2D).Therefore, the low-molecular-weight urinary proteome of 902 subjects from 10 different centers, 315 controls and 587 patients with T1D (n = 299) or T2D (n = 288), was analyzed using capillary-electrophoresis mass-spectrometry. The 261 urinary biomarkers (100 were sequenced) previously discovered in 205 subjects were validated in an additional 697 subjects to distinguish DM subjects (n = 382) from control subjects (n = 315) with 94% (95% CI: 92-95) accuracy in this study. To identify biomarkers that differentiate T1D from T2D, a subset of normoalbuminuric patients with T1D (n = 68) and T2D (n = 42) was employed, enabling identification of 131 biomarker candidates (40 were sequenced) differentially regulated between T1D and T2D. These biomarkers distinguished T1D from T2D in an independent validation set of normoalbuminuric patients (n = 108) with 88% (95% CI: 81-94%) accuracy, and in patients with impaired renal function (n = 369) with 85% (95% CI: 81-88%) accuracy. Specific collagen fragments were associated with diabetes and type of diabetes indicating changes in collagen turnover and extracellular matrix as one hallmark of the molecular pathophysiology of diabetes. Additional biomarkers including inflammatory processes and pro-thrombotic alterations were observed.These findings, based on the largest proteomic study performed to date on subjects with DM, validate the previously described biomarkers for DM, and pinpoint differences in the urinary proteome of T1D and T2D, indicating significant differences in extracellular matrix remodeling.

    View details for DOI 10.1371/journal.pone.0013051

    View details for Web of Science ID 000282210700021

    View details for PubMedID 20927192

    View details for PubMedCentralID PMC2946909

  • Epidemiology of Type 1 Diabetes ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA Maahs, D. M., West, N. A., Lawrence, J. M., Mayer-Davis, E. J. 2010; 39 (3): 481-?

    Abstract

    This article describes the epidemiology of type 1 diabetes mellitus (T1D) around the world and across the lifespan. Epidemiologic patterns of T1D by demographic, geographic, biologic, cultural, and other factors in populations are presented to gain insight about the causes, natural history, risks, and complications of T1D. Data from large epidemiologic studies worldwide indicate that the incidence of T1D has been increasing by 2% to 5% worldwide and that the prevalence of T1D is approximately 1 in 300 in the United States by 18 years of age. Research on risk factors for T1D is an active area of research to identify genetic and environmental triggers that could potentially be targeted for intervention. Although significant advances have been made in the clinical care of T1D with resultant improvements in quality of life and clinical outcomes, much more needs to be done to improve care of, and ultimately find a cure for, T1D. Epidemiologic studies have an important ongoing role to investigate the complex causes, clinical care, prevention, and cure of T1D.

    View details for DOI 10.1016/j.ecl.2010.05.011

    View details for Web of Science ID 000282146100003

    View details for PubMedID 20723815

    View details for PubMedCentralID PMC2925303

  • Lipoprotein Subfraction Cholesterol Distribution Is Proatherogenic in Women With Type 1 Diabetes and Insulin Resistance DIABETES Maahs, D. M., Hokanson, J. E., Wang, H., Kinney, G. L., Snell-Bergeon, J. K., East, A., Bergman, B. C., Schauer, I. E., Rewers, M., Eckel, R. H. 2010; 59 (7): 1771-1779

    Abstract

    Individuals with type 1 diabetes have a less atherogenic fasting lipid profile than those without diabetes but paradoxically have increased rates of cardiovascular disease (CVD). We investigated differences in lipoprotein subfraction cholesterol distribution and insulin resistance between subjects with and without type 1 diabetes to better understand the etiology of increased CVD risk.Fast protein liquid chromatography was used to fractionate lipoprotein cholesterol distribution in a substudy of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study (n = 82, age 46 +/- 8 years, 52% female, 49% with type 1 diabetes for 23 +/- 8 years). Insulin resistance was assessed by a hyperinsulinemic-euglycemic clamp.Among men, those with type 1 diabetes had less VLDL and more HDL cholesterol than control subjects (P < 0.05), but among women, those with diabetes had a shift in cholesterol to denser LDL, despite more statin use. Among control subjects, men had more cholesterol distributed as VLDL and LDL but less as HDL than women; however, among those with type 1 diabetes, there was no sex difference. Within sex and diabetes strata, a more atherogenic cholesterol distribution by insulin resistance was seen in men with and without diabetes, but only in women with type 1 diabetes.The expected sex-based less atherogenic lipoprotein cholesterol distribution was not seen in women with type 1 diabetes. Moreover, insulin resistance was associated with a more atherogenic lipoprotein cholesterol distribution in all men and in women with type 1 diabetes. This lipoprotein cholesterol distribution may contribute to sex-based differences in CVD in type 1 diabetes.

    View details for DOI 10.2337/db09-1626

    View details for Web of Science ID 000279615100027

    View details for PubMedID 20393149

    View details for PubMedCentralID PMC2889778

  • Metabolic Screening in Children Receiving Antipsychotic Drug Treatment (vol 164, pg 344, 2010) ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Morrato, E. H., Nicol, G. E., Maahs, D., Druss, B. G., Hartung, D. M., Valuck, R. J., Campagna, E., Newcomer, J. W. 2010; 164 (6): 584-584
  • Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study NEPHROLOGY DIALYSIS TRANSPLANTATION Jalal, D. I., Rivard, C. J., Johnson, R. J., Maahs, D. M., McFann, K., Rewers, M., Snell-Bergeon, J. K. 2010; 25 (6): 1865-1869

    Abstract

    Recent studies suggest that uric acid is a mediator of diabetic nephropathy. We hypothesized that elevated serum uric acid levels are a strong predictor of albuminuria in patients with type 1 diabetes.We analyzed data from the Coronary Artery Calcification in Type 1 Diabetes study, a prospective observational study. A stepwise logistic regression model was applied to predict the development of micro- or macroalbuminuria after 6 years of follow-up in 324 participants who had no evidence of micro- or macroalbuminuria at baseline. A P-value <0.1 was used as the criteria for entry into and removal from the model.The following factors were selected in the stepwise multivariate model as predictors of micro- or macroalbuminuria at the 6-year follow-up visit: baseline serum uric acid levels, HbA(1c) and pre-albuminuria. For every 1-mg/dl increase in serum uric acid levels at baseline, there was an 80% increased risk of developing micro- or macroalbuminuria at 6 years (odds ratio 1.8; 95% confidence interval 1.2, 2.8; P = 0.005). Additional covariates considered in the stepwise model were sex, age, duration of diabetes, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment, waist circumference, waist/hip ratio, body mass index, systolic and diastolic blood pressure, smoking, serum creatinine, cystatin C, high-density lipoprotein cholesterol and triglycerides.Elevated serum uric acid levels are a strong predictor of the development of albuminuria in patients with type 1 diabetes.

    View details for DOI 10.1093/ndt/gfp740

    View details for Web of Science ID 000280027400025

    View details for PubMedID 20064950

    View details for PubMedCentralID PMC2902891

  • The Use of Insulin Pumps in Youth with Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Horton, L. A., Chase, H. P. 2010; 12: S59-S65

    Abstract

    The use of insulin pump therapy (continuous subcutaneous insulin infusion) has increased dramatically in youth with type 1 diabetes (T1D) in the past decade. In this review we provide background and practical clinical advice on insulin basal rates and bolus doses and on the advantages of pump therapy with exercise. Acute complications of T1D (hypoglycemia and diabetic ketoacidosis) in the context of pump therapy are reviewed. The advantages of pump therapy in the school setting and in hospitalized patients are discussed. Finally, diabetes management in the 21st century, in which pump therapy is combined with continuous glucose monitoring, and its potential for a closed-loop pancreas are presented.

    View details for DOI 10.1089/dia.2009.0161

    View details for Web of Science ID 000278212300011

    View details for PubMedID 20515309

    View details for PubMedCentralID PMC2936259

  • Higher Fibrinogen Levels Predict Progression of Coronary Artery Calcification in Adults with Type 1 Diabetes ATHEROSCLEROSIS Rodrigues, T. C., Snell-Bergeon, J. K., Maahs, D. M., Kinney, G. L., Rewers, M. 2010; 210 (2): 671-673

    Abstract

    To determine whether fibrinogen levels predict independently progression of coronary artery calcification (CAC) in adults with type 1 diabetes.Data from a prospective cohort--the Coronary Artery Calcification in Type 1 Diabetes Study--were evaluated. Fibrinogen levels at baseline were separated into quartiles. CAC was measured twice and averaged at baseline and at follow-up 2.4+/-0.4 years later. CAC progressors were defined as participants whose square-root transformed CAC volume increased by >or=2.5 mm3 or development of clinical coronary artery disease during the follow-up period.Fibrinogen levels were higher in progressors than in non-progressors (276+/-61 mg/dl versus 259+/-61 mg/dl, p=0.0003). CAC progression, adjusted for known cardiovascular risk factors, increased in the highest quartile.Higher fibrinogen levels predict CAC progression in type 1 diabetes subjects, independent of standard cardiovascular risk factors.

    View details for DOI 10.1016/j.atherosclerosis.2009.12.034

    View details for Web of Science ID 000278036800059

    View details for PubMedID 20079495

    View details for PubMedCentralID PMC2896570

  • Metabolic Screening in Children Receiving Antipsychotic Drug Treatment ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Morrato, E. H., Nicol, G. E., Maahs, D., Druss, B. G., Hartung, D. M., Valuck, R. J., Campagna, E., Newcomer, J. W. 2010; 164 (4): 344-351

    Abstract

    To estimate metabolic screening rates, predictors of screening, and incidence of metabolic disturbances in children initiating second-generation antipsychotic (SGA) drug treatment.A retrospective, new-user cohort study (between July 1, 2004, and June 30, 2006) using Medicaid claims data.California, Missouri, and Oregon.A total of 5370 children (aged 6-17 years) without diabetes mellitus taking SGA drugs and 15,000 children without diabetes taking albuterol (control individuals) [corrected] but no SGA drugs.Findings 1 year after recommendations from the American Diabetes Association and American Psychiatric Association called for metabolic screening of patients receiving SGA drugs.Serum glucose and lipid testing, 6-month incidence of diabetes, and dyslipidemia disturbances.Glucose screening was performed in 1699 (31.6% [95% confidence interval (CI), 30.4%-32.9%]) SGA-treated children vs 1891 (12.6% [12.1%-13.2%]) control individuals. Lipid testing was performed in 720 (13.4% [95% CI, 12.5%-14.4%]) SGA-treated children vs 458 (3.1% [2.8%-3.3%]) controls. In multivariate logistic regression analysis, children with serious and/or multiple psychiatric diagnoses and those who used health care services more intensively were more likely to receive metabolic screening. The case incidence of glucose and lipid disorders was higher in SGA-treated vs albuterol-treated children (8.9 per 1000 children [95% CI, 6.6%-11.8%] vs 4.9 per 1000 children [3.9%-6.2%]; and 9.7 per 1000 children [95% CI, 7.2%-12.7%] vs 4.6 per 1000 children [95% CI, 3.6%-5.8%], respectively).Most children starting treatment with SGA medications in this public sector sample did not receive recommended glucose and lipid screening.

    View details for Web of Science ID 000276312700008

    View details for PubMedID 20368487

  • Progression to microalbuminuria in type 1 diabetes: development and validation of a prediction rule DIABETOLOGIA Vergouwe, Y., Soedamah-Muthu, S. S., Zgibor, J., Chaturvedi, N., Forsblom, C., Snell-Bergeon, J. K., Maahs, D. M., Groop, P., Rewers, M., Orchard, T. J., Fuller, J. H., Moons, K. G. 2010; 53 (2): 254-262

    Abstract

    Microalbuminuria is common in type 1 diabetes and is associated with an increased risk of renal and cardiovascular disease. We aimed to develop and validate a clinical prediction rule that estimates the absolute risk of microalbuminuria.Data from the European Diabetes Prospective Complications Study (n = 1115) were used to develop the prediction rule (development set). Multivariable logistic regression analysis was used to assess the association between potential predictors and progression to microalbuminuria within 7 years. The performance of the prediction rule was assessed with calibration and discrimination (concordance statistic [c-statistic]) measures. The rule was validated in three other diabetes studies (Pittsburgh Epidemiology of Diabetes Complications [EDC] study, Finnish Diabetic Nephropathy [FinnDiane] study and Coronary Artery Calcification in Type 1 Diabetes [CACTI] study).Of patients in the development set, 13% were microalbuminuric after 7 years. Glycosylated haemoglobin, AER, WHR, BMI and ever smoking were found to be the most important predictors. A high-risk group (n = 87 [8%]) was identified with a risk of progression to microalbuminuria of 32%. Predictions showed reasonable discriminative ability, with c-statistic of 0.71. The rule showed good calibration and discrimination in EDC, FinnDiane and CACTI (c-statistic 0.71, 0.79 and 0.79, respectively).We developed and validated a clinical prediction rule that uses relatively easily obtainable patient characteristics to predict microalbuminuria in patients with type 1 diabetes. This rule can help clinicians to decide on more frequent check-ups for patients at high risk of microalbuminuria in order to prevent long-term chronic complications.

    View details for DOI 10.1007/s00125-009-1585-3

    View details for Web of Science ID 000273084400006

    View details for PubMedID 19908023

    View details for PubMedCentralID PMC2797626

  • Oral Health Knowledge and Behaviors among Adolescents with Type 1 Diabetes. International journal of dentistry Orlando, V. A., Johnson, L. R., Wilson, A. R., Maahs, D. M., Wadwa, R. P., Bishop, F. K., Dong, F., Morrato, E. H. 2010; 2010: 942124-?

    Abstract

    Early onset and more advanced periodontal disease has been reported for children with diabetes. We surveyed oral health knowledge, attitudes, and behaviors among adolescents with diabetes in order to inform potential intervention strategies. Study subjects were youth (ages 12-19 years) with type 1 diabetes (N = 90) participating in a cohort study investigating determinants of periodontal disease at a regional pediatric diabetes specialty clinic. Over 90% of the youth had been instructed on how to brush and floss and had preventive dental care in the past year. However, 44% knew that periodontal disease is associated with diabetes and 32% knew that it can start in childhood with bleeding gums. Despite being at high risk for developing periodontal disease, the mean toothbrushing frequency was once per day and 42% did not floss. Significant opportunity exists for improving periodontal disease knowledge and adoption of preventive oral hygiene behaviors in adolescents with diabetes.

    View details for DOI 10.1155/2010/942124

    View details for PubMedID 20490262

    View details for PubMedCentralID PMC2871184

  • Relationship Between Cystatin C and Coronary Artery Atherosclerosis Progression Differs by Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Snell-Bergeon, J. K., Hokanson, J. E., Kinney, G. L., Berl, T., Rewers, M., Ogden, L. G. 2010; 12 (1): 25-33

    Abstract

    Cystatin C has been proposed to better estimate renal function and predict cardiovascular disease (CVD) than serum creatinine. To expand on our previous report, we investigated whether the relationship of cystatin C to progression of coronary artery atherosclerosis (CA) differed between individuals with type 1 diabetes (T1D) and persons without diabetes.Coronary artery calcium was measured twice over 2.4 +/- 0.4 years (n = 1,123, age = 39 +/- 9 years, 47% male, 45% T1D). Significant CA progression was defined as a > or = 2.5 increase in square root calcium volume score or development of clinical coronary artery disease. Stepwise multiple logistic regression was performed to investigate whether the association of cystatin C to CA progression differed by T1D status.The main finding and novelty of this article is that while the univariate association of cystatin C to CA progression was similar in T1D patients and persons without diabetes mellitus and in the expected direction (increased cystatin C as a biomarker of worsening renal function associated with CA progression), the association of cystatin C to progression of CA differed by T1D status (P = 0.01) after adjustment for other CVD risk factors. Unexpectedly, in persons without diabetes mellitus having relatively normal renal function, increased cystatin C was associated with decreased CA progression (odd ratio [OR] = 0.65, 95% confidence interval 0.44-0.96, P = 0.029) after adjustment, primarily due to adjustment for body mass index (BMI). Removal of BMI from this model resulted in a 49% change in the OR.Our hypothesis-generating data suggest a complex relationship among cystatin C, BMI, and CA progression that requires further study.

    View details for DOI 10.1089/dia.2009.0086

    View details for Web of Science ID 000273676100003

    View details for PubMedID 20082582

    View details for PubMedCentralID PMC2883530

  • Lifestyle risk factors for atherosclerosis in adults with type 1 diabetes DIABETES & VASCULAR DISEASE RESEARCH Bishop, F. K., Maahs, D. M., Snell-Bergeon, J. K., Ogden, L. G., Kinney, G. L., Rewers, M. 2009; 6 (4): 269-275

    Abstract

    The objective of this study was to compare the amount of self-reported physical activity, alcohol and tobacco use in a large sample of adults with type 1 diabetes and non-diabetic subjects. A second aim is to test the hypothesis that these lifestyle risk factors are associated cross-sectionally with coronary artery calcification. In 2000-2002, the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study applied validated questionnaires for smoking, alcohol and physical activity to 582 type 1 diabetes subjects and 724 non-diabetic subjects. More type 1 diabetes subjects reported current smoking than non-diabetic subjects (12.3% versus 8.6%, p=0.027). Overall, reported physical activity did not differ by diabetes status (p=0.79). More type 1 diabetes subjects reported never having consumed alcohol (10% versus 4%, p<0.0001) and those who drank consumed less alcohol (p=0.0015) than non-diabetic subjects. Physical activity and smoking were significantly associated with the presence of coronary artery calcification (adjusted OR=0.9, 95% CI: 0.8-0.996, p=0.045, and OR=1.7, CI: 1.1-2.6, p=0.03, respectively). Type 1 diabetes was independently associated with increased odds of coronary artery calcification (OR=3.5, 95% CI: 2.5-5.0, p<0.0001). Differences exist in lifestyle-related cardiovascular risk factors in men and women with type 1 diabetes compared with non-diabetic subjects in the CACTI study.

    View details for DOI 10.1177/1479164109346359

    View details for Web of Science ID 000270851400008

    View details for PubMedID 20368221

  • The Association between Adiponectin/Leptin Ratio and Diabetes Type: The SEARCH for Diabetes in Youth Study JOURNAL OF PEDIATRICS Maahs, D. M., Hamman, R. F., D'Agostino, R., Dolan, L. M., Imperatore, G., Lawrence, J. M., Marcovina, S. M., Mayer-Davis, E. J., Pihoker, C., Dabelea, D. 2009; 155 (1): 133-135

    Abstract

    We tested the association of adiponectin/leptin ratio with diabetes type after adjusting for multiple factors in 1156 youths with newly diagnosed diabetes in the SEARCH study. Although adiponectin/leptin ratio is associated with diabetes type in youth, it is due to differences in adiponectin, but not leptin levels.

    View details for DOI 10.1016/j.jpeds.2008.12.048

    View details for Web of Science ID 000267672600033

    View details for PubMedID 19559298

    View details for PubMedCentralID PMC2743881

  • Adults with type 1 diabetes eat a high-fat atherogenic diet that is associated with coronary artery calcium DIABETOLOGIA Snell-Bergeon, J. K., Chartier-Logan, C., Maahs, D. M., Ogden, L. G., Hokanson, J. E., Kinney, G. L., Eckel, R. H., Ehrlich, J., Rewers, M. 2009; 52 (5): 801-809

    Abstract

    Coronary heart disease is the leading cause of mortality among people with type 1 diabetes. Diet is an important lifestyle factor that relates to risk of CHD. The aim of this study was to examine how diet and adherence to dietary guidelines differ between adults with and without type 1 diabetes, and their correlation with CHD risk factors and coronary artery calcium (CAC).The study involved 571 people with type 1 diabetes and 696 controls, aged 19 to 56 years, who were asymptomatic for CHD. CAC was measured by electron-beam computed tomography.Compared with the controls, adults with type 1 diabetes reported a diet higher in fat, saturated fat and protein but lower in carbohydrates. Fewer than half of those with type 1 diabetes met dietary guidelines for fat and carbohydrate intake, and only 16% restricted saturated fat to less than 10% of daily energy intake. Adults with type 1 diabetes were significantly less likely to meet dietary guidelines than controls. Fat and saturated fat intakes were positively correlated, but carbohydrate intake was negatively correlated with CHD risk factors and HbA(1c). A high-fat diet and higher intake of protein were associated with greater odds of CAC, while higher carbohydrate intake was associated with reduced odds of CAC.Adults with type 1 diabetes reported consuming higher than recommended levels of fat and saturated fat. High fat intake was associated with increased CHD risk factors, worse glycaemic control and CAC. An atherogenic diet may contribute to the risk of CHD in adults with type 1 diabetes.

    View details for DOI 10.1007/s00125-009-1280-4

    View details for Web of Science ID 000264884100010

    View details for PubMedID 19219420

    View details for PubMedCentralID PMC2896567

  • Prevalence and Correlates of Depression in Individuals With and Without Type 1 Diabetes DIABETES CARE Gendelman, N., Snell-Bergeon, J. K., McFann, K., Kinney, G., Wadwa, R. P., Bishop, F., Rewers, M., Maahs, D. M. 2009; 32 (4): 575-579

    Abstract

    Depression is associated with poor glycemic control and complications in people with type 1 diabetes. We assessed the prevalence of depression and antidepressant medication use among adults with and without type 1 diabetes and the association between depression and diabetes complications.In 2006-2008, the Coronary Artery Calcification in Type 1 Diabetes Study applied the Beck Depression Inventory II (BDI-II) to 458 participants with type 1 diabetes (47% male, aged 44 +/- 9 years, type 1 diabetes duration 29 +/- 9 years) and 546 participants without diabetes (nondiabetic group) (51% male, aged 47 +/- 9 years). Use of antidepressant medication was self-reported. Depression was defined as a BDI-II score >14 and/or use of antidepressant medication. Occurrence of diabetes complications (retinopathy, blindness, neuropathy, diabetes-related amputation, and kidney or pancreas transplantation) was self-reported.Mean BDI-II score, adjusted for age and sex, was significantly higher in participants with type 1 diabetes than in nondiabetic participants (least-squares mean +/- SE: 7.4 +/- 0.3 vs. 5.0 +/- 0.3; P < 0.0001). Type 1 diabetic participants reported using more antidepressant medications (20.7 vs. 12.1%, P = 0.0003). More type 1 diabetic than nondiabetic participants were classified as depressed by BDI-II cut score (17.5 vs. 5.7%, P < 0.0001) or by either BDI-II cut score or antidepressant use (32.1 vs. 16.0%, P < 0.0001). Participants reporting diabetes complications (n = 209) had higher mean BDI-II scores than those without complications (10.7 +/- 9.3 vs. 6.4 +/- 6.3, P < 0.0001).Compared with nondiabetic participants, adults with type 1 diabetes report more symptoms of depression and more antidepressant medication usage. Depression is highly prevalent in type 1 diabetes and requires further study on assessment and treatment.

    View details for DOI 10.2337/dc08-1835

    View details for Web of Science ID 000264819800009

    View details for PubMedID 19171719

    View details for PubMedCentralID PMC2660458

  • Evaluation of Urinary Biomarkers for Coronary Artery Disease, Diabetes, and Diabetic Kidney Disease DIABETES TECHNOLOGY & THERAPEUTICS Snell-Bergeon, J. K., Maahs, D. M., Ogden, L. G., Kinney, G. L., Hokanson, J. E., Schiffer, E., Rewers, M., Mischak, H. 2009; 11 (1): 1-9

    Abstract

    In this study we sought to validate urinary biomarkers for diabetes and two common complications, coronary artery disease (CAD) and diabetic nephropathy (DN).A CAD score calculated by summing the product of a classification coefficient and signal amplitude of 15 urinary polypeptides was previously developed. Five sequences of biomarkers in the panel were identified as fragments of collagen alpha-1(I) and alpha-1(III). Prospectively collected urine samples available for analysis from 19 out of 20 individuals with CAD (15 with type 1 diabetes [T1D] and four without diabetes) and age-, sex-, and diabetes-matched controls enrolled in the Coronary Artery Calcification in Type 1 Diabetes study were analyzed for the CAD score using capillary electrophoresis and electrospray ionization mass spectrometry. Two panels of biomarkers that were previously defined to distinguish diabetes status were analyzed to determine their relationship to T1D. Three biomarker panels developed to distinguish DN (DNS) and two biomarker panels developed to distinguish renal disease (RDS) were examined to determine their relationship with renal function.The CAD score was associated with CAD (odds ratio with 95% confidence interval, 2.2 [1.3-5.2]; P = 0.0016) and remained significant when adjusted individually for age, albumin excretion rate (AER), blood pressure, waist circumference, intraabdominal fat, glycosylated hemoglobin, and lipids. DNS and RDS were significantly correlated with AER, cystatin C, and serum creatinine. The biomarker panels for diabetes were both significantly associated with T1D status (P < 0.05 for both).We validated a urinary proteome pattern associated with CAD and urinary proteome patterns associated with T1D and DN.

    View details for DOI 10.1089/dia.2008.0040

    View details for Web of Science ID 000262587100001

    View details for PubMedID 19132849

    View details for PubMedCentralID PMC2939844

  • Birth weight [corrected] and elevated albumin to creatinine ratio in youth with diabetes: the SEARCH for Diabetes in Youth study. Pediatric nephrology Maahs, D. M., Snively, B. M., Beyer, J., Imperatore, G., Bell, R., Mayer-Davis, E. J., Dolan, L. M., Pettitt, D. J., Hirsch, I., Rodriguez, B., Dabelea, D. 2008; 23 (12): 2255-2260

    Abstract

    Low birth weight (BWT) may contribute to kidney disease and could explain some of the variance in the development of early diabetic kidney disease. This hypothesis was tested in the multicenter SEARCH study (3,714 youth with diabetes <20 years of age). A morning spot urine sample, laboratory and anthropometric data, and a medical history were obtained. Elevated albumin to creatinine ratio (ACR) was defined as > or =30 mcg albumin/mg creatinine, and BWT was categorized as low (<2,500 g), reference (2,500-4,000 g), or high (>4,000 g). The relationship of BWT to elevated ACR was analyzed using multiple logistic regression. In youth with diabetes, the prevalence of elevated ACR was 12.6% in those with low BWT, 9.7% in those with reference BWT, and 8.9% in those with high BWT. BWT category was not significantly associated with elevated ACR (p = 0.23). Those with diabetes duration >18 months (2,032) had the following association of BWT category with elevated ACR [odds ratio (OR) = 1.64, 95% confidence interval (CI) 1.00-2.69, p = 0.0503] for low BWT compared with reference BWT. Whereas low BWT may be a factor in kidney disease, little evidence was found of a relationship between low BWT and elevated ACR in this study population of youth with diabetes.

    View details for DOI 10.1007/s00467-008-0921-z

    View details for PubMedID 18607639

  • Weight and elevated albumin to creatinine ratio in youth with diabetes: the SEARCH for Diabetes in Youth study PEDIATRIC NEPHROLOGY Maahs, D. M., Snively, B. M., Beyer, J., Imperatore, G., Bell, R., Mayer-Davis, E. J., Dolan, L. M., Pettitt, D. J., Hirsch, I., Rodriguez, B., Dabelea, D. 2008; 23 (12): 2255-2260
  • Dyslipidemia in Youth with Diabetes: To Treat or Not to Treat? JOURNAL OF PEDIATRICS Maahs, D. M., Wadwa, R. P., Bishop, F., Daniels, S. R., Rewers, M., Klingensmith, G. J. 2008; 153 (4): 458-465

    View details for DOI 10.1016/j.jpeds.2008.05.062

    View details for Web of Science ID 000260101600006

    View details for PubMedID 18847618

    View details for PubMedCentralID PMC2585025

  • The urinary proteome in diabetes and diabetes-associated complications: New ways to assess disease progression and evaluate therapy PROTEOMICS CLINICAL APPLICATIONS Rossing, K., Mischak, H., Rossing, P., Schanstra, J. P., Wiseman, A., Maahs, D. M. 2008; 2 (7-8): 997-1007

    Abstract

    Diabetes represents one of the main chronic diseases worldwide. Diabetes and its associated complications may be detectable even at early stages in the urinary proteome. In this article we review the current literature on urinary proteomics applied to the study of diabetes and diabetic complications. Further, we present recent data that strongly indicate urinary proteome analysis may be a valuable tool in detecting diabetes-associated pathophysiological changes at an early stage, and also may enable assessment of disease progression and efficacy of therapy. Current data indicate that collagen-derived peptides represent one of the main peptidic components in urine, which are consistently found at reduced levels in diabetes. It is tempting to speculate that this decrease in urinary collagen-derived peptides is related to an increase in extracellular matrix deposition which is a major complication in diabetes. Therefore, urinary proteome analysis might enable noninvasive assessment of this process at an early stage via determination of specific collagen fragments. This may open an avenue towards targeted therapeutic intervention.

    View details for DOI 10.1002/prca.200780166

    View details for Web of Science ID 000258088600007

    View details for PubMedID 21136900

  • Determinants of adiponectin levels in young people with Type 1 diabetes DIABETIC MEDICINE Barnes, M. M., Curran-Everett, D., Hamman, R. F., Maahs, D., Mayer-Davis, E. J., D'Agostin, R. B., West, N., Dabelea, D. 2008; 25 (3): 365-369

    Abstract

    To determine whether adiponectin levels are higher in youth with Type 1 diabetes than in non-diabetic controls, and explore potential determinants for this difference.Data are from the SEARCH for Diabetes in Youth Case-Control Study. A total of 440 youth with Type 1 diabetes and 191 non-diabetic healthy controls age 10-22 years of non-Hispanic White (NHW), African-American (AA) and Hispanic (H) origin were included in this analysis. Mean adiponectin levels were compared between persons with diabetes and controls within each racial/ethnic group, sequentially adjusting for the following variables: demographic (age, sex, Tanner stage), kidney function (albumin: creatinin ratio: ACR), obesity (body mass index: BMI; waist circumference), behavioral (percent calories from fat, physical activity), and glucose control (hemoglobin A1c: HbA(1c)).Mean adiponectin levels, adjusted for age, sex and Tanner stage, were higher in persons with Type 1 diabetes than in control subjects, among NHW (17.6 vs 13.0 microg/ml, P < 0.001) and H (17.2 vs 13.0, P = 0.01), and slightly higher but not significantly so among AA (14.5 vs 12.6, P = 0.1). The differences persisted after additionally adjusting for differences in ACR, BMI and waist circumference. We found a positive relationship between adiponectin and HbA(1c) in youth with Type 1 diabetes, even after adjustment for age, sex and race/ethnicity.Adiponectin is higher in an ethnically diverse group of youth with Type 1 diabetes than in control subjects. The relationship between glycemic control and adiponectin in Type 1 diabetes requires further exploration.

    View details for DOI 10.1111/j.1464-5491.2007.02374.x

    View details for Web of Science ID 000253609300019

    View details for PubMedID 18307464

  • A pediatric perspective: Adult problems in kids, new challenges in pediatric diabetes PEDIATRIC DIABETES Maahs, D. M., Daniels, S. R. 2007; 8 (6): 349-351

    View details for Web of Science ID 000252574000001

    View details for PubMedID 18036058

  • Serum cystatin C predicts progression of subclinical coronary atherosclerosis in individuals with type 1 diabetes DIABETES Maahs, D. M., Ogden, L. G., Kretowski, A., Snell-Bergeon, J. K., Kinney, G. L., Berl, T., Rewers, M. 2007; 56 (11): 2774-2779

    Abstract

    Renal function is an important determinant of coronary atherosclerosis, and serum cystatin C is a novel accurate measure of glomerular filtration rate (GFR) and a predictor of cardiovascular events and mortality. We hypothesized that in individuals with type 1 diabetes, cystatin C would 1) predict progression of subclinical coronary atherosclerosis (SCA) and 2) be a stronger predictor of SCA than serum creatinine, GFR (estimated by the Cockcroft-Gault [GFRCG] and Modification of Diet in Renal Disease [GFRMDRD] formulas), and albumin excretion rate.Coronary artery calcification was measured twice, using Imatron C-150 Ultrafast CT, over a 2.5 +/- 0.4-year interval in 509 adults with type 1 diabetes (42% male, age 36 +/- 9 years, duration 23 +/- 9 years). SCA progression (n = 131) was defined as a >2.5 increase in square root calcium volume score or development of clinical coronary artery disease. Predictors of SCA progression were examined in a model selected by stepwise logistic regression and an a priori-determined model. Next, each measure of renal function was inserted into the stepwise model, one at a time, and Akaike information criterion was used to compare the fit of the competing models.The stepwise model included cystatin C (odds ratio 1.44, 95% CI 1.00-2.18, P = 0.048), age, baseline coronary artery calcification, sex, diabetes duration, systolic blood pressure, and HDL. The stepwise model had a better fit than any of the competing models with serum creatinine, GFRCG, GFRMDRD, or albumin excretion rate replacing cystatin C.In individuals with type 1 diabetes, cystatin C modestly predicts SCA.

    View details for DOI 10.2337/db07-0539

    View details for Web of Science ID 000250615900018

    View details for PubMedID 17660266

  • Higher prevalence of elevated albumin excretion in youth with type 2 than type I diabetes DIABETES CARE Maahs, D. M., Snively, B. M., Bell, R. A., Dolan, L., Hirsch, I., Imperatore, G., Linder, B., Marcovina, S. M., Mayer-Davis, E. J., Pettitt, D. J., Rodriguez, B. L., Dabelea, D. 2007; 30 (10): 2593-2598

    Abstract

    To estimate the prevalence of an elevated albumin-to-creatinine ratio (ACR) (> or = 30 microg/mg) among youth with type 1 or type 2 diabetes and to identify factors associated with elevated ACR and their effect on the relationship between elevated ACR and type of diabetes.Cross-sectional data were analyzed from 3,259 participants with onset of diabetes at < 20 years of age in the SEARCH for Diabetes in Youth, a multicenter observational study of diabetes in youth. Multiple logistic regression was used to explore determinants of elevated ACR and factors accounting for differences in this prevalence between type 2 and type 1 diabetes.The prevalence of elevated ACR was 9.2% in type 1 and 22.2% in type 2 diabetes (prevalence ratio 2.4 [95% CI 1.9-3.0]; P < 0.0001). In multiple logistic regression analysis, female sex, A1C and triglyceride values, hypertension, and type of diabetes (type 2 versus type 1) were significantly associated with elevated ACR. Adjustment for variables related to insulin resistance (obesity, hypertension, dyslipidemia, and inflammation) attenuated, but did not completely explain, the association of diabetes type with elevated ACR.Youth with type 2 diabetes have a higher prevalence of elevated ACR than youth with type 1 diabetes, in an association that apparently does not completely depend on age, duration of diabetes, race/ethnicity, sex, level of glycemic control, or features of insulin resistance.

    View details for DOI 10.2337/dc07-0450

    View details for Web of Science ID 000250223400036

    View details for PubMedID 17630264

  • Determinants of serum adiponectin in persons with and without type 1 diabetes AMERICAN JOURNAL OF EPIDEMIOLOGY Maahs, D. M., Ogden, L. G., Snell-Bergeon, J. K., Kinney, G. L., Wadwal, R. P., Hokanson, J. E., Dabelea, D., Kretowskil, A., Eckel, R. H., Rewers, M. 2007; 166 (6): 731-740

    Abstract

    Low levels of adiponectin have been related to coronary heart disease, but adiponectin is higher in persons with type 1 diabetes who have an increased rate of coronary disease. In the Coronary Artery Calcification in Type 1 Diabetes Study (2000-2002), the authors investigated potential determinants of elevated adiponectin levels in persons with type 1 diabetes and whether a difference exists compared with nondiabetic persons. Serum adiponectin was measured in 1,393 persons (sex: 48% male; age: 38 (standard deviation: 9) years; diabetes duration: 23 (standard deviation: 9) years; 54% nondiabetic and 46% with type 1 diabetes). Determinants of log-transformed adiponectin levels were evaluated by multiple linear regression analysis with interaction terms to determine whether predictors of adiponectin levels differed by diabetes status. Adiponectin levels were higher in type 1 diabetic than nondiabetic persons (13.5 (standard deviation: 1.0) vs. 8.8 (standard deviation: 1.0) microg/ml; p < 0.0001), adjusting for age, gender, body mass index, and glomerular filtration rate. The final regression model explained 67% of the difference in adiponectin levels between type 1 diabetic and nondiabetic persons. The variables explaining this difference included high density lipoprotein cholesterol, albumin excretion rate, plasminogen activator inhibitor-1, and hemoglobin A1c level. Adiponectin is higher in type 1 diabetic than nondiabetic persons. Although some of the difference can be explained, further study is needed to better understand the relation between elevated adiponectin levels and patient outcomes, including coronary heart disease.

    View details for DOI 10.1093/aje/kwm125

    View details for Web of Science ID 000249328600014

    View details for PubMedID 17591595

  • ACE-I/ARB treatment in type 1 diabetes patients with albuminuria is associated with lower odds of progression of coronary artery calcification JOURNAL OF DIABETES AND ITS COMPLICATIONS Maahs, D. M., Snell-Bergeon, J. K., Kinney, G. L., Wadwa, R. P., Garg, S., Ogden, L. G., Rewers, M. 2007; 21 (5): 273-279

    Abstract

    The objective of this study was to determine whether baseline albuminuria predicts coronary artery calcification (CAC) progression in subjects with type 1 diabetes and whether angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II type I receptor blocker (ARB) treatment is associated with lower odds of CAC progression.In 2000-2002, the Coronary Artery Calcification in Type 1 Diabetes study enrolled 652 subjects with type 1 diabetes who were between 19 and 56 years old and had no known history of coronary artery disease (CAD). In this analysis, CAC progression over 2.5+/-0.4 years was evaluated in 478 subjects (age=37+/-9 years; male=45%; diabetes duration=23+/-9 years) at a follow-up visit. Albuminuria was defined by American Diabetes Association criteria, and microalbuminuria and macroalbuminuria were combined for the analysis. Logistic regression was used to evaluate the relationship between baseline categorical presence of albuminuria and CAC progression.At baseline, of the 478 subjects, 157 (33%) were on ACE-I/ARB treatment and 83 (17%) had albuminuria, with 114 (24%) having CAC progression at follow-up. In backward logistic regression, presence of albuminuria at baseline predicted progression of CAC among subjects not treated with ACE-I/ARB [odds ratio=4.06; 95% confidence interval (CI)=1.45-11.35; P=.008]. Among the subjects with albuminuria, the odds of progression was 62% lower (95% CI=88% decrease to 23% increase; P=.106) in those treated with ACE-I/ARB.Albuminuria is a significant independent risk factor for CAC progression in young type 1 diabetes patients asymptomatic for CAD, and ACE-I/ARB treatment is associated with substantially lower odds of CAC progression.

    View details for DOI 10.1016/j.jdiacomp.2006.04.004

    View details for Web of Science ID 000249622500001

    View details for PubMedID 17825750

  • Polymorphisms of the renin-angiotensin system genes predict progression of subclinical coronary atherosclerosis DIABETES Kretowski, A., McFann, K., Hokanson, J. E., Maahs, D., Kinney, G., Snell-Bergeon, J. K., Wadwa, R. P., Eckel, R. H., Ogden, L., Garg, S., Li, J., Cheng, S., Erlich, H. A., Rewers, M. 2007; 56 (3): 863-871

    Abstract

    Premature coronary artery disease (CAD) in subjects with type 1 diabetes dramatically affects quality of life and morbidity and leads to premature death, but there is still little known about the mechanisms and predictors of this complication. In the present study, we explored the role of genetic variants of angiotensinogen (AGT, M235T), ACE (I/D), and angiotensin type 1 receptor (ATR1, A1166C) as predictors of rapid progression of subclinical coronary atherosclerosis. Five-hundred eighty-five type 1 diabetic patients and 592 similar age and sex control subjects were evaluated for progression of coronary artery calcification (CAC), a marker of subclinical CAD, before and after a 2.5-year follow-up. In logistic regression analysis, CAC progression was dramatically more likely in type 1 diabetic subjects not treated with ACE inhibitor/angiotensin receptor blocker who had the TT-ID-AA/AC genotype combination than in those with other genotypes (odds ratio 11.6 [95%CI 4.5-29.6], P < 0.0001) and was even stronger when adjusted for cardiovascular disease risk factors and the mean A1C (37.5 [3.6-388], P = 0.002). In conclusion, a combination of genotype variants of the renin-angiotensin system genes is a powerful determinant of subclinical progression of coronary artery atherosclerosis in type 1 diabetic patients and may partially explain accelerated CAD in type 1 diabetes.

    View details for DOI 10.2337/db06-1321

    View details for Web of Science ID 000244827500037

    View details for PubMedID 17327458

  • Longitudinal lipid screening and use of lipid-lowering medications in pediatric type 1 diabetes JOURNAL OF PEDIATRICS Maahs, D. M., Wadwa, R. P., McFann, K., Nadeau, K., Williams, M. R., Eckel, R. H., Klingensmith, G. J. 2007; 150 (2): 146-150

    Abstract

    Because cardiovascular disease (CVD) is the leading cause of death in patients with type 1 diabetes (T1D) and dyslipidemia is an important CVD risk factor, we investigated dyslipidemia and its treatment in children with T1D.Subjects had T1D (n = 360), repeated lipid measurements (n = 1095; mean, 3.04 +/- 0.94; range, 2 to 11), and were seen between 1994 and 2004. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and non-HDL cholesterol (non-HDL) were categorized on the basis of published guidelines. Age, diabetes duration, sex, body mass index, HbA1c, and lipid-lowering medication use were recorded. Predictors of TC, HDL, and non-HDL were determined.Sustained abnormalities existed for TC > or = 200 mg/dL (16.9%); HDL < 35 mg/dL (3.3%); and non-HDL > or = 130 mg/dL (27.8%), > or = 160 mg/dL (10.6%), and > or = 190 mg/dL (3.3%). Lipid-lowering medications were started on 23 patients. In mixed model longitudinal data analyses, HbA1c was significantly related to TC and non-HDL. Body mass index z-score was inversely related to HDL.In this retrospective, longitudinal study of pediatric patients with T1D with repeated lipid measurements, sustained abnormal levels for TC, HDL, and non-HDL were present. Prospective longitudinal data for dyslipidemia in youth with T1D are needed.

    View details for DOI 10.1016/j.jpeds.2006.10.054

    View details for Web of Science ID 000244111300009

    View details for PubMedID 17236891

  • Editorial: Mortality and renal disease in type 1 diabetes mellitus- Progress made, more to be done JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Maahs, D. M., Rewers, M. 2006; 91 (10): 3757-3759

    View details for DOI 10.1210/jc.2006-1730

    View details for Web of Science ID 000241100900008

    View details for PubMedID 17028289

  • The apolipoprotein A-IV Gln360His polymorphism predicts progression of coronary artery calcification in patients with type 1 diabetes DIABETOLOGIA Kretowski, A., Hokanson, J. E., McFann, K., Kinney, G. L., Snell-Bergeon, J. K., Maahs, D. M., Wadwa, R. P., Eckel, R. H., Ogden, L. G., Garg, S. K., Cheng, J. L., Erlich, H. A., Rewers, M. 2006; 49 (8): 1946-1954

    Abstract

    Individuals with type 1 diabetes have an increased incidence of coronary artery disease (CAD) and a higher risk of cardiovascular death compared with individuals of the same age in the general population. While chronic hyperglycaemia and insulin resistance partially explain excess CAD, little is known about the potential genetic determinants of accelerated coronary atherosclerosis in type 1 diabetes. The aim of the present study was to evaluate the association of apolipoprotein A-IV (APOA4) polymorphisms with coronary artery calcification (CAC) progression, a marker of subclinical atherosclerosis.Two previously well-studied functional APOA4 polymorphisms resulting in the substitution of the amino acid Thr for Ser at codon 347 and Gln for His at codon 360 were genotyped in 634 subjects with type 1 diabetes and 739 non-diabetic control subjects, the participants of the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) study.The His360 allele was associated with a significantly higher risk of CAC progression among patients with type 1 diabetes (33.7 vs 21.2%, p=0.014), but not in the control subjects (14.1 vs 11.1%, p=0.42). Logistic regression analysis confirmed that the presence of the APOA4 His360 allele predicts an increased risk of progression of coronary atherosclerosis in adults with type 1 diabetes of long duration (odds ratio = 3.3, p=0.003 after adjustment for covariates associated with CAD risk). CONCLUSIONS /INTERPRETATION: This is the first report suggesting an association between the APOA4 Gln360His polymorphism and risk of CAC progression in subjects with type 1 diabetes. Additional studies are needed to explore potential interactions between APOA4 genotypes and metabolic/oxidative stress components of the diabetic milieu leading to rapid progression of atherosclerosis.

    View details for DOI 10.1007/s00125-006-0317-1

    View details for Web of Science ID 000238859900028

    View details for PubMedID 16770585

  • Assessing weight-related quality of life in adolescents OBESITY Kolotkin, R. L., Zeller, M., Modi, A. C., Samsa, G. P., Quinlan, N. P., Yanovski, J. A., Bell, S. K., Maahs, D. M., de Serna, D. G., Roehrig, H. R. 2006; 14 (3): 448-457

    Abstract

    The development of a new weight-related measure to assess quality of life in adolescents [Impact of Weight on Quality of Life (IWQOL)-Kids] is described.Using a literature search, clinical experience, and consultation with pediatric clinicians, 73 items were developed, pilot tested, and administered to 642 participants, 11 to 19 years old, recruited from weight loss programs/studies and community samples (mean z-BMI, 1.5; range, -1.2 to 3.4; mean age, 14.0; 60% female; 56% white). Participants completed the 73 items and the Pediatric Quality of Life Inventory and were weighed and measured.Four factors (27 items) were identified (physical comfort, body esteem, social life, and family relations), accounting for 71% of the variance. The IWQOL-Kids demonstrated excellent psychometric properties. Internal consistency coefficients ranged from 0.88 to 0.95 for scales and equaled 0.96 for total score. Convergent validity was demonstrated with strong correlations between IWQOL-Kids total score and the Pediatric Quality of Life Inventory (r = 0.76, p < 0.0001). Significant differences were found across BMI groups and between clinical and community samples, supporting the sensitivity of this measure. Participants in a weight loss camp demonstrated improved IWQOL-Kids scores, suggesting responsiveness of the IWQOL-Kids to weight loss/social support intervention.The present study provides preliminary evidence regarding the psychometric properties of the IWQOL-Kids, a weight-related quality of life measure for adolescents. Given the rise of obesity in youth, the development of a reliable and valid weight-related measure of quality of life is timely.

    View details for Web of Science ID 000250566800015

    View details for PubMedID 16648616

    View details for PubMedCentralID PMC2374918

  • Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents. Endocrine practice Maahs, D., De Serna, D. G., Kolotkin, R. L., Ralston, S., Sandate, J., Qualls, C., Schade, D. S. 2006; 12 (1): 18-28

    Abstract

    To evaluate the efficacy of orlistat to enhance weight loss in obese adolescents.The study was a 6-month randomized, double-blind, placebo-controlled trial to compare the effects of orlistat (120 mg orally 3 times a day) and placebo on reduction of body mass index (BMI). Forty adolescents between 14 and 18 years of age with a mean BMI of 40 kg/m2 entered the protocol between December 2002 and February 2003. Study subjects stayed overnight in the General Clinical Research Center, during which dietary records were reviewed and lifestyle recommendations were given. The study participants received either orlistat (120 mg orally 3 times a day) or placebo and were assessed monthly for 6 months. At 0, 3, and 6 months, fasting laboratory tests were performed. The primary end point was the change in BMI from baseline to 6 months. Secondary outcomes included changes in weight, lean body mass, and results of blood chemistry studies.No statistically significant difference was noted between the 2 study groups for decrease in BMI from baseline to 6 months (P = 0.39). The decrease in BMI within the orlistat group (-1.3 +/- 1.6 kg/m2; P = 0.04) and within the placebo group (-0.8 +/- 3.0 kg/m2; P = 0.02), however, was statistically significant. Laboratory measurements did not differ between the 2 groups. In comparison with the placebo group, the orlistat group had increased adverse events, primarily gastrointestinal symptoms and findings.In this study of obese adolescents, orlistat did not significantly reduce BMI in comparison with placebo at 6 months.

    View details for PubMedID 16524859

  • Soluble interleukin-2 receptor as a marker for progression of coronary artery calcification in type 1 diabetes INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY Wadwa, R. P., Kinney, G. L., Ogden, L., Snell-Bergeon, J. K., Maahs, D. M., Cornell, E., Tracy, R. P., Rewers, M. 2006; 38 (5-6): 996-1003

    Abstract

    Soluble interleukin-2 receptor (sIL2r), a marker of T cell activation, is elevated in inflammatory processes, such as rheumatoid arthritis, hepatitis and neoplasm. We explored a potential association between plasma sIL2r levels and progression of coronary artery calcification (CAC), a marker for subclinical atherosclerosis, in a prospectively followed cohort of type 1 diabetic and non-diabetic subjects, aged 20-59 years, with no history of coronary artery disease.CAC progression was assessed by electron beam tomography over 2.6 years (range 1.6-3.2). Plasma sIL2r levels were measured in a nested case-control substudy of 98 subjects (67 diabetic, 31 non-diabetic) with and 173 subjects (84 diabetic, 89 non-diabetic) without significant CAC progression. Log-transformed sIL2r levels were analyzed by conditional logistic regression to compare subjects with and without significant CAC progression.SIL2r was a significant predictor for CAC progression after adjusting for presence of baseline CAC, age, gender, diabetes status, baseline calcium volume score and adiponectin (OR 1.99, 95% CI 1.09-3.61, p = 0.02 for a doubling of sIL2r level). Addition of BMI, LDL, HDL, hypertension, smoking status, HbA1c, CRP, fibrinogen, homocysteine and PAI-1 to regression models weakened but did not remove sIL2r as a predictor of CAC progression. There was no indication that this effect was different by diabetes status (p = 0.6 for diabetes-sIL2r interaction).Elevated plasma sIL2r is associated with CAC progression independent of traditional coronary artery disease risk factors in type 1 diabetic and non-diabetic young adults. SIL2r should be considered as a novel marker of inflammation leading to coronary artery disease.

    View details for DOI 10.1016/j.biocel.2005.09.015

    View details for Web of Science ID 000236525800029

    View details for PubMedID 16271309

  • Total cholesterol and high-density lipoprotein levels in pediatric subjects with type 1 diabetes mellitus JOURNAL OF PEDIATRICS Maahs, D. M., Maniatis, A. K., Nadeau, K., Wadwa, R. P., McFann, K., Klingensmith, G. J. 2005; 147 (4): 544-546

    Abstract

    This study reports serum lipid levels in 682 children with type 1 diabetes mellitus. We found that 3.5% of the subjects had a high-density lipoprotein (HDL) cholesterol level < 35 mg/dL, 15.4% had a total cholesterol (TC) level>200 mg/dL, and 18.6% were abnormal for either HDL or TC, compared with prevalences of 5.7%, 11.2%, and 16.3%, respectively, reported in the National Health and Nutrition Examination Survey 2001-02. Hemoglobin A1c value was significantly related to TC and non-HDL cholesterol levels.

    View details for DOI 10.1016/j.jpeds.2005.04.068

    View details for Web of Science ID 000232865300028

    View details for PubMedID 16227045

  • Awareness and treatment of dyslipidemia in young adults with type 1 diabetes DIABETES CARE Wadwa, R. P., Kinney, G. L., Maahs, D. M., Snell-Bergeon, J., Hokanson, J. E., Garg, S. K., Eckel, R. H., Rewers, M. 2005; 28 (5): 1051-1056

    Abstract

    Dyslipidemia is a preventable major risk factor for coronary heart disease (CHD). Despite an increased risk of CHD in type 1 diabetes, little is known concerning awareness and adequacy of dyslipidemia treatment in this population. In this report, we describe the prevalence of dyslipidemia and adequacy of pharmacological treatment in patients with type 1 diabetes and comparable nondiabetic subjects.From 2000 to 2002, the Coronary Artery Calcification in Type 1 Diabetes study obtained fasting lipid profiles in 1,416 individuals aged 19-56 years with no history of CHD: 652 type 1 diabetic patients (46% men, mean age 37 +/- 9 years) and 764 nondiabetic control subjects (50% men, mean age 39 +/- 9 years). These data combined with patient questionnaire results were used to determine prevalence of dyslipidemia and adequacy of pharmacological treatment. For all subjects, dyslipidemia was defined using National Cholesterol Education Program Adult Treatment Panel III criteria.Type 1 diabetic subjects had significantly less dyslipidemia than nondiabetic control subjects (47 vs. 58%, P < 0.001), and a higher percentage of those with abnormal lipids were aware of (52 vs. 34%, P < 0.0001), on medication for (36 vs. 9%, P < 0.0001), and in control of their lipid levels (15 vs. 1.4%, P < 0.001). Of those on treatment, control was achieved in 41% of type 1 diabetic subjects and 15% of nondiabetic participants (P < 0.01).Dyslipidemia, a major risk factor for CHD, remains largely undiagnosed and undertreated in high-risk populations, such as patients with type 1 diabetes.

    View details for Web of Science ID 000228701100011

    View details for PubMedID 15855566

  • Low plasma adiponectin levels predict progression of coronary artery calcification CIRCULATION Maahs, D. M., Ogden, L. G., Kinney, G. L., Wadwa, P., Snell-Bergeon, J. K., Dabelea, D., Hokanson, J. E., Ehrlich, J., Eckel, R. H., Rewers, M. 2005; 111 (6): 747-753

    Abstract

    Circulating adiponectin levels are lower in men than in women and lower in advanced coronary artery disease, obesity, and type 2 but not type 1 diabetes. However, it is not known whether low adiponectin levels predict development of atherosclerosis independently of other cardiovascular risk factors.Progression of coronary artery calcification (CAC) over an average of 2.6 years (range, 1.6 to 3.3) was assessed in a cohort of patients with type 1 diabetes and nondiabetic subjects 19 to 59 years of age. In this nested case-control substudy, plasma adiponectin levels were measured in 101 cases with significant CAC progression and in 205 controls. Controls were oversampled on the basis of age, gender, diabetes status, and presence of baseline CAC. In conditional logistic regression adjusted for baseline CAC volume and other significant predictors of CAC progression, adiponectin levels were inversely related to progression of CAC in diabetic (OR, 0.47; 95% CI, 0.24 to 0.94) and nondiabetic (OR, 0.15; 95% CI, 0.05 to 0.40 for a doubling in adiponectin levels) subjects. Adjustment for additional cardiovascular risk factors did not change this association. In conditional logistic regression models by quartiles of plasma adiponectin levels, the probability value for trend was statistically significant for all participants (P<0.001) and nondiabetic participants (P<0.001) and was borderline for type 1 diabetics (P=0.08).Low plasma adiponectin levels are associated with progression of CAC in type 1 diabetic and nondiabetic subjects independently of other cardiovascular risk factors.

    View details for DOI 10.1161/01.CIR.0000155251.03724.A5

    View details for Web of Science ID 000227007800007

    View details for PubMedID 15699257

  • Hypertension prevalence, awareness, treatment, and control in an adult type 1 diabetes population and a comparable general population DIABETES CARE Maahs, D. M., Hokanson, J., Kinney, G. L., Ehrlich, J., Wadwa, P., Garg, S., Snell-Bergeon, J. K., Eckel, R. H., Dabelea, D., Rewers, M. J. 2005; 28 (2): 301-306

    Abstract

    To compare the prevalence, awareness, treatment, and control of hypertension in a population-representative sample of adults with type 1 diabetes and comparable nondiabetic control subjects.In 2000-2002, the Coronary Artery Calcification in Type 1 Diabetes Study enrolled 1,416 individuals aged 19-56 years with no known history of coronary artery disease: 652 type 1 diabetic patients (46% male, mean age 37 years) and 764 nondiabetic control subjects (50% male, mean age 39 years). Subjects were asked if they had been told by a physician that they had hypertension or were on a blood pressure medication. Blood pressure was measured using standardized Joint National Committee (JNC) protocol.Type 1 diabetic subjects, compared with nondiabetic subjects, had higher rates of hypertension prevalence (43 vs. 15%, P < 0.001), awareness (53 vs. 45%, P = 0.11), treatment (87 vs. 47%, P < 0.001), and control (55 vs. 32%, P < 0.001) for the JNC 6 goal (130/85 mmHg). Only 42% of all type 1 diabetic hypertensive subjects met the new JNC 7 goal (130/80 mmHg). Type 1 diabetic subjects had better blood pressure control (72 vs. 32%, P < 0.0001), using 140/90 mmHg as a common measure. The majority of treated subjects were on a single antihypertensive agent (75 vs. 64%).Subjects with type 1 diabetes have higher rates of hypertension prevalence, treatment, and control than nondiabetic subjects. However, hypertension remains largely uncontrolled, even if treated in high-risk populations, such as type 1 diabetic subjects and undiagnosed individuals in the general population. Achieving more stringent blood pressure goals will require increased attention and may necessitate the use of multiple antihypertensive agents.

    View details for Web of Science ID 000226612900011

    View details for PubMedID 15677783