In 2016 I moved to become Professor of Pediatrics and Division Chief of Pediatric Endocrinology at Stanford University. My research interest is to improve care and prevent complications in people with type 1 diabetes (T1D). I was co-author with Dr Peter Chase on the 12th and 13th editions of Understanding Diabetes, or Pink Panther education books. Specifically, my research has extended from epidemiologic studies identifying targets to development of clinical trials to test interventions. My NIDDK sponsored K23 “Cardiovascular Disease in Type 1 Diabetes Mellitus: Young Adults to Adolescents” focused on cardiovascular and kidney complications in young adults with T1D. I continued this work as part of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study with Drs. Marian Rewers and Janet Snell-Bergeon and in the pediatric population with Dr. Paul Wadwa and as investigator with the Search for Diabetes in Youth study. I am a past co-Chair for Protocols and Publications with the Type 1 Diabetes Exchange and continue as a Steering Committee member and director of international collaborations which complements my role as Secretary-General for ISPAD. While in Colorado I was local PI on PERL, an RCT to prevent early kidney function decline with Drs Michael Mauer (UMinnesota) and Alessandro Doria (Joslin) as PIs. I am a PI on FL3X, an innovative behavioral intervention for adolescents with T1D with Drs. Elizabeth Mayer-Davis (UNC) and Michael Seid (Cincinnati). As a logical extension of this research to prevent T1D complications, my research has increasingly focused on the development of the artificial pancreas as improved glucose control is the best proven method to prevent T1D complications. In Colorado I was the local PI on 3 UC4 funded artificial pancreas studies and I continue this research at Stanford with Drs Bruce Buckingham and Korey Hood. I work with clinical and engineering collaborators at RPI, JAEB, Sansum/UCSB, Yale, UVa, Cambridge, Boston University, and UC-Boulder on JDRF, NIDDK, and NSF funded studies as listed below. I was co-PI with Dr. Klingensmith on the Barbara Davis Center T32 and K12 training grants in Pediatric Endocrinology. I am Associate Director of the Stanford University Diabetes Research Center with Drs Seung Kim (Director) and Frederic Kraemer https://sdrc.stanford.edu .
- Pediatric Endocrinology
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)
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)
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)
Children, adolescents, and young adults with diabetes internationally
Opportunities for Student Involvement
Remote Monitoring of Diabetes in Young Children With Type 1 Diabetes
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).
Application of Zone Model Predictive Control Artificial Pancreas During Extended Use of Infusion Set and Sensor: A Randomized Crossover-Controlled Home-Use Trial.
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.
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 2017; 19 (S2): S37-S43
Outpatient Closed-Loop Control with Unannounced Moderate Exercise in Adolescents Using Zone Model Predictive Control.
Diabetes technology & therapeutics
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
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
2017; 43 (2): 223-232
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
2017; 12 (3)
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.
2017; 40 (3): 359-366
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 2017; 19 (S1): S105-S119
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
2017; 31 (2): 387-389
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 2017; 31 (2): 369-374
Predictors of Dyslipidemia Over Time in Youth With Type 1 Diabetes: For the SEARCH for Diabetes in Youth Study.
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
Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women.
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.
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
Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs)
2017; 17 (1)
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
Severe hypoglycemia rates are not associated with HbA1c: a cross-sectional analysis of 3 contemporary pediatric diabetes registry databases.
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
Ambulatory glucose profile analysis of the juvenile diabetes research foundation continuous glucose monitoring dataset-Applications to the pediatric diabetes population.
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
Characteristics of youth with type 1 diabetes (T1D) with and without a parent with T1D in the T1D exchange clinic registry.
Journal of diabetes
2016; 8 (6): 834-838
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 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
2016; 10 (6): 1216-1221
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
2016; 10 (6): 1268-1276
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
A survey of youth with new onset type 1 diabetes: Opportunities to reduce diabetic ketoacidosis.
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
2016; 122: 28-37
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
2016; 17: 38-45
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
2016: ajprenal 00415 2016-?
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
2016; 30 (6): 1093-1096
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
Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry
2016; 17 (5): 327-336
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.
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
2016; 18 (7): 429-435
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
Outcome Measures for Artificial Pancreas Clinical Trials: A Consensus Report.
2016; 39 (7): 1175-1179
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
Reduced brachial artery distensibility in patients with type 1 diabetes
JOURNAL OF DIABETES AND ITS COMPLICATIONS
2016; 30 (5): 893-897
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
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
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
The dose-response effect of insulin sensitivity on albuminuria in children according to diabetes type
2016; 31 (6): 933-940
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
Lipoprotein subfraction cholesterol distribution is more atherogenic in insulin resistant adolescents with type 1 diabetes
2016; 17 (4): 257-265
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
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.
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
2016; 30 (4): 586-590
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
Hyperfiltration and uricosuria in adolescents with type 1 diabetes
2016; 31 (5): 787-793
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
In-home nighttime predictive low glucose suspend experience in children and adults with type 1 diabetes.
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
- Measuring glomerular filtration rate by iohexol clearance on filter paper is feasible in adolescents with type 1 diabetes in the ambulatory setting ACTA DIABETOLOGICA 2016; 53 (2): 331-333
Prevalence of cardiovascular risk factors in youth with type 1 diabetes and elevated body mass index.
2016; 53 (2): 271-277
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
2016; 87 (4): 376-384
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
Profound hypokalemia associated with severe diabetic ketoacidosis
2016; 17 (1): 61-65
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
- Progress in Diabetes Technology: Developments in Insulin Pumps, Continuous Glucose Monitors, and Progress towards the Artificial Pancreas JOURNAL OF PEDIATRICS 2016; 169: 13-20
Development and Validation of a Method to Estimate Insulin Sensitivity in Patients With and Without Type 1 Diabetes
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2016; 101 (2): 686-695
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
- Diabetes Technology and Therapy in the Pediatric Age Group DIABETES TECHNOLOGY & THERAPEUTICS 2016; 18: S86-S100
Therapeutic inertia: underdiagnosed and undertreated hypertension in children participating in the T1D Exchange Clinic Registry
2016; 17 (1): 15-20
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
2016; 16 (2)
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
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
2016; 59 (1): 87-91
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
Comparing Two Waist-to-Height Ratio Measurements with Cardiometabolic Risk Factors among Youth with Diabetes.
International journal of child health and nutrition
2016; 5 (3): 87-94
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
Influences of gender on cardiovascular disease risk factors in adolescents with and without type 1 diabetes.
International journal of pediatric endocrinology
2016; 2016: 8-?
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
Rates of Diabetic Ketoacidosis: International Comparison With 49,859 Pediatric Patients With Type 1 Diabetes From England, Wales, the US, Austria, and Germany
2015; 38 (10): 1876-1882
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
2015; 116 (7): 1057-1062
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
Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with Type 1 diabetes
NEPHROLOGY DIALYSIS TRANSPLANTATION
2015; 30 (10): 1706-1711
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
Update on Estimation of Kidney Function in Diabetic Kidney Disease
CURRENT DIABETES REPORTS
2015; 15 (9)
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
- Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis (vol 38, pg 1197, 2015) DIABETES CARE 2015; 38 (9): 1813-1813
Obesity in Youth with Type 1 Diabetes in Germany, Austria, and the United States
JOURNAL OF PEDIATRICS
2015; 167 (3): 627-?
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
2015; 58 (9): 1993-2002
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
- ISPAD Clinical Practice Consensus Guidelines 2014 Compendium: Type 2 diabetes in the child and adolescent (vol 15, pg 26, 2014) PEDIATRIC DIABETES 2015; 16 (5): 392-392
Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2015; 26 (8): 1999-2010
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
Adiponectin-SOGA Dissociation in Type 1 Diabetes
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2015; 100 (8): E1065-E1073
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
Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis
2015; 38 (7): 1197-1204
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
Association of apolipoprotein B, LDL-C and vascular stiffness in adolescents with type 1 diabetes
2015; 52 (3): 611-619
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
Diabetes Complications in Childhood Diabetes-New Biomarkers and Technologies.
Current pediatrics reports
2015; 3 (2): 177-186
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
Factors Associated with Nocturnal Hypoglycemia in At-Risk Adolescents and Young Adults with Type 1 Diabetes
DIABETES TECHNOLOGY & THERAPEUTICS
2015; 17 (6): 385-391
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
Flexible Lifestyles for Youth (FL3X) behavioural intervention for at-risk adolescents with Type 1 diabetes: a randomized pilot and feasibility trial
2015; 32 (6): 829-833
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
Current State of Type 1 Diabetes Treatment in the US: Updated Data From the T1D Exchange Clinic Registry
2015; 38 (6): 971-978
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
Change in adiposity minimally affects the lipid profile in youth with recent onset type 1 diabetes
2015; 16 (4): 280-286
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
- Refining the Closed Loop in the Data Age: Research-to-Practice Transitions in Diabetes Technology DIABETES TECHNOLOGY & THERAPEUTICS 2015; 17 (5): 304-306
- 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 2015; 38 (4)
- DIABETES Elevated risk of mortality in type 1 diabetes mellitus NATURE REVIEWS ENDOCRINOLOGY 2015; 11 (3): 136-137
Insulin sensitivity and complications in type 1 diabetes: New insights.
World journal of diabetes
2015; 6 (1): 8-16
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
Achieving International Society for Pediatric and Adolescent Diabetes and American Diabetes Association clinical guidelines offers cardiorenal protection for youth with type 1 diabetes.
2015; 16 (1): 22-30
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 2015; 16 (1): 22-30
Estimated insulin sensitivity predicts regression of albuminuria in Type 1 diabetes
2015; 32 (2): 257-261
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
Renal Function Is Associated With Peak Exercise Capacity in Adolescents With Type 1 Diabetes
2015; 38 (1): 126-131
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
- Towards a Verified Artificial Pancreas: Challenges and Solutions for Runtime Verification RUNTIME VERIFICATION, RV 2015 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
2014; 8 (6): 576-583
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
Insulin Sensitivity Is an Important Determinant of Renal Health in Adolescents With Type 2 Diabetes
2014; 37 (11): 3033-3039
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
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
2014; 28 (6): 762-766
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
A novel method to detect pressure-induced sensor attenuations (PISA) in an artificial pancreas.
Journal of diabetes science and technology
2014; 8 (6): 1091-1096
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
Predicting major outcomes in type 1 diabetes: a model development and validation study
2014; 57 (11): 2304-2314
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
- Cardiovascular Disease Risk Factors in Youth With Diabetes Mellitus A Scientific Statement From the American Heart Association CIRCULATION 2014; 130 (17): 1532-U224
Multicenter Closed-Loop/Hybrid Meal Bolus Insulin Delivery with Type 1 Diabetes
DIABETES TECHNOLOGY & THERAPEUTICS
2014; 16 (10): 623-632
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
Serum uric acid predicts vascular complications in adults with type 1 diabetes: the coronary artery calcification in type 1 diabetes study
2014; 51 (5): 783-791
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
FREQUENCY OF CONTINUOUS GLUCOSE MONITORING USE AND CHANGE IN HEMOGLOBIN A1C FOR ADULTS WITH TYPE 1 DIABETES IN A CLINICAL PRACTICE SETTING
2014; 20 (10): 1007-1015
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
2014; 37 (10): 2702-2709
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
- Type 2 diabetes in the child and adolescent PEDIATRIC DIABETES 2014; 15: 26-46
- Assessment and management of hypoglycemia in children and adolescents with diabetes PEDIATRIC DIABETES 2014; 15: 180-192
- ISPAD Clinical Practice Consensus Guidelines 2014. Type 2 diabetes in the child and adolescent. Pediatric diabetes 2014; 15: 26-46
- Introduction to ISPAD Clinical Practice Consensus Guidelines 2014 Compendium PEDIATRIC DIABETES 2014; 15: 1-3
- Introduction to the limited care guidance appendix PEDIATRIC DIABETES 2014; 15: 279-280
- ISPAD Clinical Practice Consensus Guidelines 2014. Assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatric diabetes 2014; 15: 180-192
- The delivery of ambulatory diabetes care to children and adolescents with diabetes PEDIATRIC DIABETES 2014; 15: 86-101
- ISPAD Clinical Practice Consensus Guidelines 2014. The delivery of ambulatory diabetes care to children and adolescents with diabetes. Pediatric diabetes 2014; 15: 86-101
A practical method to measure GFR in people with type 1 diabetes
JOURNAL OF DIABETES AND ITS COMPLICATIONS
2014; 28 (5): 667-673
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 2014; 15: 102-114
- ISPAD Clinical Practice Consensus Guidelines 2014. Assessment and monitoring of glycemic control in children and adolescents with diabetes. Pediatric diabetes 2014; 15: 102-114
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
2014; 57 (8): 1578-1585
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
2014; 21 (4): 279-286
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
Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy
NEPHROLOGY DIALYSIS TRANSPLANTATION
2014; 29 (8): 1563-1570
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
- A Randomized Trial of a Home System to Reduce Nocturnal Hypoglycemia in Type 1 Diabetes DIABETES CARE 2014; 37 (7): 1885-1891
Depression in Adults in the T1D Exchange Clinic Registry
2014; 37 (6): 1563-1572
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
2014; 7 (2): 197-205
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
Serum uric acid and insulin sensitivity in adolescents and adults with and without type 1 diabetes
JOURNAL OF DIABETES AND ITS COMPLICATIONS
2014; 28 (3): 298-304
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
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
2014; 16 (5): 284-291
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
Frequency of Morning Ketosis After Overnight Insulin Suspension Using an Automated Nocturnal Predictive Low Glucose Suspend System
2014; 37 (5): 1224-1229
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
- Update: Ambulatory Blood Pressure Monitoring in Children and Adolescents A Scientific Statement From the American Heart Association HYPERTENSION 2014; 63 (5): 1116-1135
Fasting Blood Glucose-A Missing Variable for GFR-Estimation in Type 1 Diabetes?
2014; 9 (4)
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
Serum Uric Acid and Hypertension in Adults: A Paradoxical Relationship in Type 1 Diabetes
JOURNAL OF CLINICAL HYPERTENSION
2014; 16 (4): 283-288
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
Ideal Cardiovascular Health and the Prevalence and Progression of Coronary Artery Calcification in Adults With and Without Type 1 Diabetes
2014; 37 (2): 521-528
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
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
2014; 13: 59-?
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
Changes in diet and physical activity in adolescents with and without type 1 diabetes over time.
International journal of pediatric endocrinology
2014; 2014 (1): 17-?
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
Early Diabetic Nephropathy A complication of reduced insulin sensitivity in type 1 diabetes
2013; 36 (11): 3678-3683
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
Correlates of Medical Nutrition Therapy and Cardiovascular Outcomes in Youth With Type 1 Diabetes
JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR
2013; 45 (6): 661-668
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
Albuminuria According to Status of Autoimmunity and Insulin Sensitivity Among Youth With Type 1 and Type 2 Diabetes
2013; 36 (11): 3633-3638
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
- The Association between Vitamin D and Vascular Stiffness in Adolescents with and without Type 1 Diabetes PLOS ONE 2013; 8 (10)
Factors Associated With Microalbuminuria in 7,549 Children and Adolescents With Type 1 Diabetes in the T1D Exchange Clinic Registry
2013; 36 (9): 2639-2645
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
Impaired Renal Function Further Increases Odds of 6-Year Coronary Artery Calcification Progression in Adults With Type 1 Diabetes: The CACTI study
2013; 36 (9): 2607-2614
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
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
2013; 15 (8): 622-627
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
2013; 13 (4): 550-559
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
Severe Hypoglycemia and Diabetic Ketoacidosis in Adults With Type 1 Diabetes: Results From the T1D Exchange Clinic Registry
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2013; 98 (8): 3411-3419
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
2013; 8 (7)
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
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
2013; 36 (7): 2035-2037
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
Prospective Association Between Inflammatory Markers and Progression of Coronary Artery Calcification in Adults With and Without Type 1 Diabetes
2013; 36 (7): 1967-1973
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
- 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 2013; 2 (1): 21-38
BENEFITS OF ACCELEROMETER AND HEART RATE DATA FOR HYPOGLYCEMIA MITIGATION
MARY ANN LIEBERT INC. 2013: A93–A93
View details for Web of Science ID 000315467200257
Estimated Insulin Sensitivity and Cardiovascular Disease Risk Factors in Adolescents with and without Type 1 Diabetes
JOURNAL OF PEDIATRICS
2013; 162 (2): 297-301
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
USING ACTIVITY MONITORS TO IMPROVE CGM SENSOR ANOMALY DETECTION
MARY ANN LIEBERT INC. 2013: A2–A2
View details for Web of Science ID 000315467200005
The association between vitamin D and vascular stiffness in adolescents with and without type 1 diabetes.
2013; 8 (10)
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
The Importance of Palmitoleic Acid to Adipocyte Insulin Resistance and Whole-Body Insulin Sensitivity in Type 1 Diabetes
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2013; 98 (1): E40-E50
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
Glucose Control Predicts 2-Year Change in Lipid Profile in Youth with Type 1 Diabetes
JOURNAL OF PEDIATRICS
2013; 162 (1): 101-U127
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
Lower A1c among adolescents with lower perceived A1c goal: a cross-sectional survey.
International journal of pediatric endocrinology
2013; 2013 (1): 17-?
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
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
2012; 112 (11): 1736-1746
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
Implementation of proteomic biomarkers: making it work
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
2012; 42 (9): 1027-1036
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
2012; 6 (5): 1142-1147
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
Outpatient Assessment of Determinants of Glucose Excursions in Adolescents with Type 1 Diabetes: Proof of Concept
DIABETES TECHNOLOGY & THERAPEUTICS
2012; 14 (8): 658-664
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
- Early Detection of Kidney Disease in Type 1 Diabetes: What Do We Really Know? DIABETES TECHNOLOGY & THERAPEUTICS 2012; 14 (7): 541-544
Cardiovascular Disease in Children and Adolescents with Diabetes: Where Are We, and Where Are We Going?
DIABETES TECHNOLOGY & THERAPEUTICS
2012; 14: S11-S21
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
- Current Knowledge and Future Directions on Cardiovascular Disease in Diabetes DIABETES TECHNOLOGY & THERAPEUTICS 2012; 14: S75-S76
- Cardiovascular Disease (CVD) Limbo: How Soon and Low Should We Go to Prevent CVD in Diabetes? DIABETES TECHNOLOGY & THERAPEUTICS 2012; 14 (6): 449-452
Features of Hepatic and Skeletal Muscle Insulin Resistance Unique to Type 1 Diabetes
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2012; 97 (5): 1663-1672
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
Adiponectin Dysregulation and Insulin Resistance in Type 1 Diabetes
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
2012; 97 (4): E642-E647
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
Novel Urinary Protein Biomarkers Predicting the Development of Microalbuminuria and Renal Function Decline in Type 1 Diabetes
2012; 35 (3): 549-555
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
- Update on care of children with type 1 diabetes. Advances in pediatrics 2012; 59 (1): 303-327
- Is Carbohydrate Counting Enough? Towards Perfection or Unwanted Complexity? DIABETES TECHNOLOGY & THERAPEUTICS 2012; 14 (1): 3-5
Lessons learned from a lipid lowering trial in adolescents with type 1 diabetes.
International journal of pediatric endocrinology
2012; 2012 (1): 24-?
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
Sugar-sweetened and diet beverage consumption is associated with cardiovascular risk factor profile in youth with type 1 diabetes
2011; 48 (4): 275-282
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
Age and Sex Influence Cystatin C in Adolescents With and Without Type 1 Diabetes
2011; 34 (11): 2360-2362
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
Childhood obesity and cardiovascular disease: links and prevention strategies
NATURE REVIEWS CARDIOLOGY
2011; 8 (9): 513-525
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
Uric Acid as a Mediator of Diabetic Nephropathy
SEMINARS IN NEPHROLOGY
2011; 31 (5): 459-465
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
- Prevention of Overweight/Obesity as a Strategy to Optimize Cardiovascular Health CIRCULATION 2011; 124 (7): 840-850
Systematic Shifts in Cystatin C Between 2006 and 2010
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2011; 6 (8): 1952-1955
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
Lipoprotein-Associated Phospholipase A(2) Activity Predicts Progression of Subclinical Coronary Atherosclerosis
DIABETES TECHNOLOGY & THERAPEUTICS
2011; 13 (3): 381-387
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
Correlates of Dietary Intake in Youth with Diabetes: Results from the SEARCH for Diabetes in Youth Study
JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR
2011; 43 (2): 123-129
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
Association of insulin sensitivity to lipids across the lifespan in people with Type 1 diabetes
2011; 28 (2): 148-155
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
Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease
2011; 79 (1): 128-134
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
Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes The CACTI Study
2011; 60 (1): 306-314
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
Development, validation and use of an insulin sensitivity score in youths with diabetes: the SEARCH for Diabetes in Youth study
2011; 54 (1): 78-86
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
- Report of the 36th ISPAD meeting, Buenos Aires, Argentina, 27-30 October 2010 PEDIATRIC DIABETES 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
2010; 27 (12): 1436-1442
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
Association of glycaemia with lipids in adults with type 1 diabetes: modification by dyslipidaemia medication
2010; 53 (12): 2518-2525
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
Serum Uric Acid Predicts Progression of Subclinical Coronary Atherosclerosis in Individuals Without Renal Disease
2010; 33 (11): 2471-2473
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
Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals
JOURNAL OF HYPERTENSION
2010; 28 (11): 2316-2322
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
2010; 5 (9)
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
Epidemiology of Type 1 Diabetes
ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
2010; 39 (3): 481-?
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
Lipoprotein Subfraction Cholesterol Distribution Is Proatherogenic in Women With Type 1 Diabetes and Insulin Resistance
2010; 59 (7): 1771-1779
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
Metabolic Screening in Children Receiving Antipsychotic Drug Treatment (vol 164, pg 344, 2010)
ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
2010; 164 (6): 584-584
View details for Web of Science ID 000278324300018
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
2010; 25 (6): 1865-1869
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
The Use of Insulin Pumps in Youth with Type 1 Diabetes
DIABETES TECHNOLOGY & THERAPEUTICS
2010; 12: S59-S65
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
Higher Fibrinogen Levels Predict Progression of Coronary Artery Calcification in Adults with Type 1 Diabetes
2010; 210 (2): 671-673
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
Metabolic Screening in Children Receiving Antipsychotic Drug Treatment
ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
2010; 164 (4): 344-351
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
2010; 53 (2): 254-262
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
Oral Health Knowledge and Behaviors among Adolescents with Type 1 Diabetes.
International journal of dentistry
2010; 2010: 942124-?
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
Relationship Between Cystatin C and Coronary Artery Atherosclerosis Progression Differs by Type 1 Diabetes
DIABETES TECHNOLOGY & THERAPEUTICS
2010; 12 (1): 25-33
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
Lifestyle risk factors for atherosclerosis in adults with type 1 diabetes
DIABETES & VASCULAR DISEASE RESEARCH
2009; 6 (4): 269-275
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
2009; 155 (1): 133-135
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
Adults with type 1 diabetes eat a high-fat atherogenic diet that is associated with coronary artery calcium
2009; 52 (5): 801-809
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
Prevalence and Correlates of Depression in Individuals With and Without Type 1 Diabetes
2009; 32 (4): 575-579
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
Evaluation of Urinary Biomarkers for Coronary Artery Disease, Diabetes, and Diabetic Kidney Disease
DIABETES TECHNOLOGY & THERAPEUTICS
2009; 11 (1): 1-9
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
Birth weight [corrected] and elevated albumin to creatinine ratio in youth with diabetes: the SEARCH for Diabetes in Youth study.
2008; 23 (12): 2255-2260
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 2008; 23 (12): 2255-2260
- Dyslipidemia in Youth with Diabetes: To Treat or Not to Treat? JOURNAL OF PEDIATRICS 2008; 153 (4): 458-465
The urinary proteome in diabetes and diabetes-associated complications: New ways to assess disease progression and evaluate therapy
PROTEOMICS CLINICAL APPLICATIONS
2008; 2 (7-8): 997-1007
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
2008; 25 (3): 365-369
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 2007; 8 (6): 349-351
Serum cystatin C predicts progression of subclinical coronary atherosclerosis in individuals with type 1 diabetes
2007; 56 (11): 2774-2779
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
2007; 30 (10): 2593-2598
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
2007; 166 (6): 731-740
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
2007; 21 (5): 273-279
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
2007; 56 (3): 863-871
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
2007; 150 (2): 146-150
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 2006; 91 (10): 3757-3759
The apolipoprotein A-IV Gln360His polymorphism predicts progression of coronary artery calcification in patients with type 1 diabetes
2006; 49 (8): 1946-1954
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
2006; 14 (3): 448-457
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
Soluble interleukin-2 receptor as a marker for progression of coronary artery calcification in type 1 diabetes
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
2006; 38 (5-6): 996-1003
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
Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents.
2006; 12 (1): 18-28
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
Total cholesterol and high-density lipoprotein levels in pediatric subjects with type 1 diabetes mellitus
JOURNAL OF PEDIATRICS
2005; 147 (4): 544-546
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
2005; 28 (5): 1051-1056
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
2005; 111 (6): 747-753
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
2005; 28 (2): 301-306
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