I grew up in the east bay area and have had type 1 diabetes for 30+ years. I studied electrical engineering and computer science at U.C. Berkeley (Go Bears!) with the hope of applying my knowledge to diabetes technology. The significance of clinical practice became clear to me after my siblings also developed diabetes. I am devoting my life to advancing the care of diabetes in people of all ages.

Clinical Focus

  • Endocrinology
  • Diabetes and Metabolism

Academic Appointments

Administrative Appointments

  • Member, Stanford Diabetes Research Center (2020 - Present)

Honors & Awards

  • Stephen Bechtel Endowed Fellow, Stanford Maternal and Child Health Research Institute (2017-2019)
  • Alpha Omega Alpha, National medical honor society (2017)
  • Outstanding Teaching as a House Officer, University of Southern California (2014)
  • Gold Humanism Honor Society, Gold Foundation (2011)

Boards, Advisory Committees, Professional Organizations

  • Consultant, Abbott Diabetes Care (2018 - Present)
  • Medical Advisory Board, Consultant, Tidepool (2018 - Present)
  • Medical Advisor, Biolinq (2019 - Present)
  • Medical Monitor, Capillary Biomedical (2020 - Present)
  • Advisory Board, Provention Bio (2021 - 2021)
  • Medical Advisor, Gluroo (2021 - Present)

Professional Education

  • Board Certification: American Board of Pediatrics, Pediatric Endocrinology (2019)
  • Board Certification: American Board of Internal Medicine, Endocrinology, Diabetes and Metabolism (2018)
  • Fellowship: Stanford University Endocrinology Fellowship (2019) CA
  • Fellowship: Stanford University Pediatric Endocrinology Fellowship (2019) CA
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2015)
  • Board Certification: American Board of Pediatrics, Pediatrics (2015)
  • Residency, Chief Residency, LAC+USC, Internal Medicine & Pediatrics (2015)
  • Medical Education: University of California Davis School of Medicine (2011) CA

Clinical Trials

  • Investigational Extended Wear Insulin Infusion Set in People With Type 1 Diabetes Recruiting

    The purpose of this study is to collect clinical data to support a 7-day wear of the Extended Wear Infusion Set (EWIS). Participants will be asked to: 1. Wear the EWIS for up to 7 consecutive days for 12 consecutive wear periods 2. Perform blood glucose and ketone measurements if continuous glucose meter is ≥250mg/dL for one hour

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  • Evaluating the Benefits of Physiologic Insulin Delivery Not Recruiting

    In normal physiology insulin is secreted by beta cells into the portal vein. There have been a number of purported benefits among long-term intraperitoneal insulin users. In the present study we will inject ultra-rapid acting insulin into the upper and lower peritoneum under ultrasound guidance and compare it to subcutaneous injection. We will measure glucose, insulin and glucagon following these injections, to assess for benefits in counter-regulatory hormone production and insulin pharmacokinetics.

    Stanford is currently not accepting patients for this trial.

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  • Evaluation of Extended Wear Infusion Set With 670G Hybrid Closed-Loop Therapy Not Recruiting

    This is a randomized trial to determine if an extended wear infusion set can be worn for up to 7 days with a hybrid closed-loop system in adult with Type 1 Diabetes

    Stanford is currently not accepting patients for this trial. For more information, please contact Liana Hsu, BS, 650-725-3939.

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  • Evaluation of the Advanced Hybrid Closed Loop (AHCL) System in Type 1 Adults and Pediatrics Utilizing Lyumjev® Not Recruiting

    This US study will evaluate the safety and effectiveness of utilizing insulin Lyumjev® lispro-aabc in the MiniMed™ 780G System in Type 1 adult and pediatric subjects in a home setting to support product and system labeling.

    Stanford is currently not accepting patients for this trial.

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  • Safety and Effectiveness of the MiniMed™ 780G System With DS5 CGM Not Recruiting

    The purpose of this study is to confirm the safety and effectiveness of the MiniMed 780G insulin pump used in combination with the DS5 CGM in type 1 diabetes adult and pediatric subjects in a home setting.

    Stanford is currently not accepting patients for this trial. For more information, please contact Bailey Suh, 925-389-8516.

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  • Safety Evaluation of an Advanced Hybrid Closed Loop System Using Lyumjev With the Tandem t:Slim X2 Insulin Pump With Control-IQ Technology in Adults, Adolescents and Children With Type 1 Diabetes Not Recruiting

    Prospective, multi-center, single-arm study in adults and children ages 6 to 80 with type 1 diabetes to evaluate the safety of Lyumjev with Control-IQ technology to achieve labeling updates for Lyumjev and the t:slim X2 insulin pump.

    Stanford is currently not accepting patients for this trial. For more information, please contact Liana Hsu, 650-725-3939.

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2021-22 Courses

Stanford Advisees

All Publications

  • COVID-19 impacts and inequities among underserved communities with diabetes. Journal of clinical & translational endocrinology Maizel, J. L., Haller, M. J., Maahs, D. M., Addala, A., Lal, R. A., Filipp, S. L., Gurka, M. J., Westen, S., Dixon, B. N., Figg, L., Hechavarria, M., Malden, K. G., Walker, A. F. 2024; 36: 100337


    People with diabetes have higher COVID-19 morbidity and mortality. These risks are amplified for underserved communities including racial/ethnic minorities and people with lower socioeconomic status. However, limited research has examined COVID-19 outcomes specifically affecting underserved communities with diabetes.From November 2021 to July 2022, adults with insulin-requiring diabetes at federally qualified health centers in Florida and California (n = 450) completed surveys examining COVID-19 outcomes and demographics. Surveys assessed COVID-19 severity, vaccination uptake, mask-wearing habits, income changes, and healthcare access changes. Surveys also included the full Coronavirus Anxiety Scale (CAS-19). Descriptive statistics were computed for all outcomes. Between-group comparisons for state and race/ethnicity were evaluated via Chi-Squared, Fisher's Exact, Cochran-Mantel-Haenszel, One-Way ANOVA, and t-tests. Logistic regression determined factors associated with COVID-19 vaccination uptake. Data were self-reported and analyzed cross-sectionally.Overall, 29.7 % reported contracting COVID-19; of those, 45.3 % sought care or were hospitalized. Most (81.3 %) received ≥ 1 vaccine. Hispanics had the highest vaccination rate (91.1 %); Non-Hispanic Blacks (NHBs) had the lowest (73.9 %; p =.0281). Hispanics had 4.63x greater vaccination odds than Non-Hispanic Whites ([NHWs]; 95 % CI = [1.81, 11.89]). NHWs least often wore masks (18.8 %; p <.001). Participants reported pandemic-related healthcare changes (62 %) and higher costs of diabetes medications (41 %). Income loss was more frequent in Florida (76 %; p <.001). NHBs most frequently reported "severe" income loss (26.4 %; p =.0124). Loss of health insurance was more common among NHBs (13.3 %; p =.0416) and in Florida (9.7 %; p =.039). COVID-19 anxiety was highest among NHBs and Hispanics (IQR = [0.0, 3.0]; p =.0232) and in Florida (IQR = [0.0, 2.0]; p =.0435).Underserved communities with diabetes had high COVID-19 vaccine uptake but experienced significant COVID-19-related physical, psychosocial, and financial impacts. NHBs and those in Florida had worse outcomes than other racial/ethnic groups and those in California. Further research, interventions, and policy changes are needed to promote health equity for this population.

    View details for DOI 10.1016/j.jcte.2024.100337

    View details for PubMedID 38559803

    View details for PubMedCentralID PMC10973684

  • Multicenter Evaluation of Ultra-Rapid Lispro (URLi) Insulin with Control-IQ Technology in Adults, Adolescents and Children with Type 1 Diabetes. Diabetes technology & therapeutics Levy, C., Bailey, R., Laffel, L. M., Forlenza, G. P., DiMeglio, L. A., Hughes, M. S., Brown, S., Aleppo, G., Bhargava, A., Shah, V., Clements, M. A., Kipnes, M. S., Bruggeman, B., Daniels, M., Rodriguez, H., Calhoun, P., Lum, J., Sasson-Katchalski, R., Pinsker, J. E., Pollom, R., Beck, R. W. 2024


    To evaluate the safety and explore the efficacy of use of ultra-rapid lispro (URLi, Lyumjev) insulin in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology in children, teens and adults living with type 1 diabetes (T1D).At 14 U.S. diabetes centers, youth and adults with T1D completed a 16-day lead-in period using lispro in a t:slim X2 insulin pump with Control-IQ 1.5 technology followed by a 13-week period in which URLi insulin was used in the pump.The trial included 179 individuals with type 1 diabetes (T1D) age 6 to 75 years. With URLi, 1.7% (3 participants) had a severe hypoglycemia event over 13 weeks attributed to override boluses or a missed meal. No DKA events occurred. Two participants stopped URLi use due to infusion site discomfort and one stopped after developing a rash. Mean time 70-180 mg/dL (TIR) increased from 65%±15% with lispro to 67%±13% with URLi (P=0.004). Mean insulin treatment satisfaction questionnaire (ITSQ) score improved from 75±13 at screening to 80±11 after 13 weeks of URLi use (mean difference = 6; 95% CI 4 to 8; P<0.001), with the greatest improvement reported for confidence avoiding symptoms of high blood sugar. Mean treatment related impact measure-diabetes (TRIM-D) score improved from 74±12 to 80±12 (P<0.001), and mean TRIM-Diabetes Device (TRIM-DD) score improved from 82±11 to 86±12 (P<0.001).URLi use in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology was safe for adult and pediatric participants with type 1 diabetes, with quality of life benefits of URLi use perceived by the study participants.

    View details for DOI 10.1089/dia.2024.0048

    View details for PubMedID 38696672

  • Development of a Real-time Force-based Algorithm for Infusion Failure Detection. Journal of diabetes science and technology Blanco, L. E., Wilcox, J. H., Hughes, M. S., Lal, R. A. 2024: 19322968241247530


    Continuous subcutaneous insulin infusion (CSII) is a common treatment option for people with diabetes (PWD), but insulin infusion failures pose a significant challenge, leading to hyperglycemia, diabetes burnout, and increased hospitalizations. Current CSII pumps' occlusion alarm systems are limited in detecting infusion failures; therefore, a more effective detection method is needed.We conducted five preclinical animal studies to collect data on infusion failures, utilizing both insulin and non-insulin boluses. Data were captured using in-line pressure and flow rate sensors, with additional force data from CSII pumps' onboard sensors in one study. A novel classifier model was developed using this dataset, aimed at detecting different types of infusion failures through direct utilization of force sensor data. Performance was compared against various occlusion alarm thresholds from commercially available CSII pumps.The testing dataset included 251 boluses. The Bagging classifier model showed the highest performance metrics among the models tested, exhibiting high accuracy (96%), sensitivity (94%), and specificity (98%), with lower false-positive and false-negative rate compared with traditional occlusion alarm pressure thresholds.Our study developed a novel non-threshold classifier that outperforms current occlusion alarm systems in CSII pumps in detecting infusion failures. This advancement has the potential to reduce the risk of hyperglycemia and hospitalizations due to undetected infusion failures, offering a more reliable and effective CSII therapy for PWD. Further studies involving human participants are recommended to validate these findings and assess the classifier's performance in a real-world setting.

    View details for DOI 10.1177/19322968241247530

    View details for PubMedID 38654491

  • Insulin Delivery Hardware: Pumps and Pens. Diabetes technology & therapeutics Lal, R., Leelarathna, L. 2024; 26 (S1): S32-S44

    View details for DOI 10.1089/dia.2024.2503

    View details for PubMedID 38441453

  • A cysteine-specific solubilizing tag strategy enables efficient chemical protein synthesis of difficult targets. Chemical science Li, W., Jacobsen, M. T., Park, C., Jung, J. U., Lin, N. P., Huang, P. S., Lal, R. A., Chou, D. H. 2024; 15 (9): 3214-3222


    We developed a new cysteine-specific solubilizing tag strategy via a cysteine-conjugated succinimide. This solubilizing tag remains stable under common native chemical ligation conditions and can be efficiently removed with palladium-based catalysts. Utilizing this approach, we synthesized two proteins containing notably difficult peptide segments: interleukin-2 (IL-2) and insulin. This IL-2 chemical synthesis represents the simplest and most efficient approach to date, which is enabled by the cysteine-specific solubilizing tag to synthesize and ligate long peptide segments. Additionally, we synthesized a T8P insulin variant, previously identified in an infant with neonatal diabetes. We show that T8P insulin exhibits reduced bioactivity (a 30-fold decrease compared to standard insulin), potentially contributing to the onset of diabetes in these patients. In summary, our work provides an efficient tool to synthesize challenging proteins and opens new avenues for exploring research directions in understanding their biological functions.

    View details for DOI 10.1039/d3sc06032b

    View details for PubMedID 38425513

    View details for PubMedCentralID PMC10901488

  • Use of the Community-Derived Open-Source Automated Insulin Delivery Loop System in Type 2 Diabetes. Diabetes technology & therapeutics Bauza, C., Kanapka, L. G., Greene, E., Lal, R. A., Arbiter, B., Beck, R. W. 2024


    No published data are available on the use of the community-derived open-source Loop hybrid closed-loop controller ("Loop") by individuals with type 2 diabetes (T2D). Via social media postings, we invited individuals with T2D currently using the Loop system to join an observational study. Thirteen responded of whom 7 were eligible for the study, were using the Loop algorithm, and provided data. Mean (±SD) age was 61±13 years and mean body mass index was 31±5 kg/m2. All but one participant were using noninsulin glucose-lowering medications. Self-reported mean hemoglobin A1c (HbA1c) decreased from 7.3±1.1% prior to starting Loop to 6.0±0.5% on Loop. Time in range 70-180 mg/dL increased from 84% to 93%. The amount of time in hypoglycemia was extremely low prior to and with Loop (time <54 mg/dL was 0.04±0.06% versus 0.09±0.07%, respectively). No severe hypoglycemia or diabetic ketoacidosis events were reported while using Loop. These data, though limited, suggest that the Loop system is likely to be effective when used by individuals with T2D and should be evaluated in large scale studies.

    View details for DOI 10.1089/dia.2023.0569

    View details for PubMedID 38386434

  • A cysteine-specific solubilizing tag strategy enables efficient chemical protein synthesis of difficult targets CHEMICAL SCIENCE Li, W., Jacobsen, M. T., Park, C., Jung, J., Lin, N., Huang, P., Lal, R. A., Chou, D. 2024

    View details for DOI 10.1039/d3sc06032b

    View details for Web of Science ID 001147767400001

  • Following in Banting's footsteps or straying from the path? Observations from contemporary diabetes innovation. Frontiers in endocrinology Leadley, C., Addala, A., Berkeley, J., Crocket, H., Davis, E. A., Hewapathirana, N., Hussain, S., Lal, R., Lomax, K., Wilkinson, T., de Bock, M., Burckhardt, M. A. 2023; 14: 1270517


    While advancements in the treatment of diabetes continue to rapidly evolve, many of the newer technologies have financial barriers to care, opposing the egalitarian ethos of Banting who sold his patent on insulin for a nominal cost to allow it to be made widely available. Inequity in access to new therapies drives disparity in diabetes burden with potential for these gaps to widen in the future. The 2023 International Conference on Advanced Technologies and Treatments of Diabetes (ATTD) presented ground-breaking and current research in diabetes technology. Oral presentations of the ATTD conference 2023 were analyzed to describe what percentage of speakers discussed equity in their talks. Overall, less than a quarter of presenters discussed equity, though there was regional variation. To ensure that diabetes technologies reduce disparity and improve outcomes, we encourage future speakers at diabetes (technology) conferences to consider equity of diabetes care and incorporate this into their presentations.

    View details for DOI 10.3389/fendo.2023.1270517

    View details for PubMedID 38033993

    View details for PubMedCentralID PMC10686253

  • Breaking a feedback loop: A reassessment of an investigator initiated OS-AID study. Diabetes, obesity & metabolism Braune, K., Hussain, S., Lal, R., Leibrand, S., Lewis, D. M., O'Donnell, S. 2023

    View details for DOI 10.1111/dom.15301

    View details for PubMedID 37795622

  • Recruiting historically under-represented individuals into Project ECHO Diabetes: using barrier analysis to understand disparities in clinical research in the USA. BMJ open Addala, A., Hechavarria, M., Figg, L., Roque, X., Filipp, S. L., Anez-Zabala, C., Lal, R., Gurka, M. J., Haller, M. J., Maahs, D. M., Walker, A. F. 2023; 13 (8): e072546


    Individuals under-recruited in diabetes research studies include those not seen at endocrinology centres and those from rural, low socioeconomic and/or under-represented racial/ethnic groups. The purpose of this descriptive analysis is to detail recruitment and retention efforts of Project ECHO Diabetes clinical sites affiliated with Stanford University and University of Florida.Prospective collection of participant engagement and qualitative analysis of barriers and facilitators of research engagement within Project ECHO Diabetes, a virtual tele-education programme for healthcare providers in the management of individuals with insulin-requiring diabetes.Data were collected at the patient level, provider level and clinic level between 1 May 2021 and 31 July 2022.Participants and study personnel were recruited from 33 Project ECHO Diabetes sites in California and Florida.We report study completion rates for participants recruited into 33 Project ECHO Diabetes sites. Using barrier analysis, a methodology designed for the real-time assessment of interventions and system processes to identify barriers and facilitators, study personnel identified significant barriers to recruitment and retention and mapped them to actionable solutions.In total, 872 participants (California n=495, Florida n=377) were recruited with differing recruitment rates by site (California=52.7%, Florida=21.5%). Barrier analysis identified lack of trust, unreliable contact information, communication issues and institutional review board (IRB) requirements as key recruitment barriers. Culturally congruent staff, community health centre (CHC) support, adequate funding and consent process flexibility were solutions to address recruitment challenges. Barriers to retention were inconsistent postal access, haemoglobin A1c kit collection challenges, COVID-19 pandemic and broadband/connectivity issues. Additional funding supporting research staff and analogue communication methods were identified as solutions address barriers to retention.Funded partnerships with CHCs, trusted by their local communities, were key in our recruitment and retention strategies. IRB consent process flexibility reduced barriers to recruitment. Recruiting historically under-represented populations is feasible with funding aimed to address structural barriers to research participation.

    View details for DOI 10.1136/bmjopen-2023-072546

    View details for PubMedID 37648378

  • Automated Insulin Delivery with Remote Real-Time Continuous Glucose Monitoring for Hospitalized Patients with Diabetes: A Multi-Center, Single-arm, Feasibility Trial. Diabetes technology & therapeutics Davis, G. M., Hughes, M. S., Brown, S., Sibayan, J., Perez-Guzman, M. C., Stumpf, M., Thompson, Z., Basina, M., Patel, R., Hester, J., Abraham, A., Ly, T. T., Chaney, C., Tan, M., Hsu, L. J., Kollman, C., Beck, R. W., Lal, R. A., Buckingham, B. A., Pasquel, F. 2023


    Introduction Multiple daily injection (MDI) insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote glucose monitoring offers a solution to these shortcomings. Research Design and Methods In a single-arm multicenter pilot trial, we tested the feasibility, safety, and effectiveness of the Omnipod 5 AID System with real-time continuous glucose monitoring (CGM) for up to 10 days in hospitalized patients with insulin-requiring requiring diabetes on non-ICU medical-surgical units. Primary endpoints included the proportion of time in automated mode and percent time in range (TIR, 70-180 mg/dl) among participants with >48 hours of CGM data. Safety endpoints included incidence of severe hypoglycemia and diabetes-related ketoacidosis (DKA). Additional glycemic endpoints, CGM accuracy, and patient satisfaction were also explored. Results Twenty-two participants were enrolled; eighteen used the system for a total of 96 days (mean 5.3±3.1 days per patient), and sixteen had sufficient CGM data required for analysis. Median percent time in automated mode was 95% (IQR 92-98%) for the 18 system users, and the 16 participants with >48 hours of CGM data achieved an overall TIR of 68±16%, with 0.17±0.3% time <70 mg/dl and 0.06±0.2% time <54 mg/dl. Sensor mean glucose was 167±21 mg/dl. There were no DKA or severe hypoglycemic events. All participants reported satisfaction with the system at study end. Conclusions The use of AID with a disposable tubeless patch-pump along with remote real-time CGM is feasible in the hospital setting.

    View details for DOI 10.1089/dia.2023.0304

    View details for PubMedID 37578778

  • Multisite Quality Improvement Program Within the Project ECHO Diabetes Remote Network. Joint Commission journal on quality and patient safety Wang, C. J., Lewit, E. M., Clark, C. L., Lee, F. W., Maahs, D. M., Haller, M. J., Addala, A., Lal, R. A., Cuttriss, N., Baer, L. G., Figg, L. E., Anez-Zabala, C., Sheehan, E. P., Westen, S. C., Bernier, A. V., Donahoo, W. T., Walker, A. F. 2023


    BACKGROUND: The telementoring Project ECHO (Extension for Community Healthcare Outcomes) model has been shown to improve disease management in diabetes in many underserved communities. The authors aim to evaluate if ECHO could also be an effective tool for quality improvement (QI) of diabetes care in these communities.METHODS: Thirteen clinics in underserved communities in California and Florida participating in Project ECHO Diabetes were recruited for a 12-month QI program. The program provided weekly tele-education sessions, including a didactic presentation and case-based discussion. In addition, clinics chose their own set of quality measures to improve and met remotely to discuss their efforts, successes, and setbacks every quarter with mentorship from QI experts.RESULTS: Of the 31 QI initiatives attempted by different clinics, all had either made improvements (25 initiatives, 80.6%) or were in the process of making improvements (6 initiatives, 19.4%) in structural, process, and outcome measures. Examples of these measures include whether clinics have protocols to identify high-risk patients (structure), numbers of continuous glucose monitor prescriptions submitted by the clinics (process), and percentage of patients with diabetes whose most recent HbA1c are > 9% (outcome). For one measure, 40.0% of the clinics had achieved a higher percentage of cumulative HbA1c measurement in the third quarter of the year, compared to the fourth quarter in the previous year. The cost of QI implementation varied widely due to different number of personnel involved across sites.CONCLUSION: A QI program delivered via Project ECHO Diabetes can facilitate quality improvements in underserved communities.

    View details for DOI 10.1016/j.jcjq.2023.08.001

    View details for PubMedID 37718146

  • The Promising Success of Project Extension for Community Healthcare Outcomes (ECHO) Diabetes: Case Series. JMIR diabetes Figg, L., Addala, A., Jain, I., Anez, C., Midney, P., DeChirico, C., Symanski, C., Fitzgerald, B. C., Colbert, K., Raymer, T., Stockton-Joreteg, C., Murphy, E., Collins, L., Bernstein, C., Hechavarria, M., Sheehan, E. P., Bernier, A., Westen, S. C., Hood, K. K., Zaharieva, D. P., Basina, M., Cuttriss, N., Filipp, S. L., Gurka, M. J., Walker, A. F., Maahs, D. M., Haller, M. J., Lal, R. A. 2023; 8: e46050


    In the United States, there are over 37 million people with diabetes but only 8000 endocrinologists. Therefore, many people with diabetes receive care exclusively from primary care providers (PCPs). To democratize knowledge regarding insulin-requiring diabetes through tele-education, Stanford University and the University of Florida developed Project Extension for Community Healthcare Outcomes (ECHO) Diabetes.ECHO Diabetes uses a Hub and Spoke model connecting specialists (the "Hub") with PCPs (the "Spokes"). One-hour, weekly sessions include Hub diabetes didactic presentations and Spoke deidentified case presentations. Lessons learned during these sessions target provider knowledge and confidence surrounding diabetes management and patient care.Spokes were asked to provide short descriptions of people with diabetes whose diabetes management improved directly or indirectly from their providers' participation or their involvement with a Diabetes Support Coach (DSC). We provide a case series to describe individuals and outcomes. Because this study was not a randomized controlled trial and was a prospective observation of patients with the intervention delivered to providers, the trial is not registered in a public trials registry.A case series of 11 people with diabetes was compiled from 10 PCPs and 1 DSC from California and Florida between 2021 and 2022. The principal impact of ECHO Diabetes is the education amplified from PCPs and DSCs to people with diabetes. In all cases, people with diabetes reported increased engagement and improved diabetes management. Several cases reflected increased access to diabetes technology, improvement in glycemic outcomes, and positive trends in mental health measures.This case series elucidates the potential value of the ECHO Diabetes program to people with diabetes who receive their diabetes care from PCPs. Those matched with a DSC saw clinically significant improvements in hemoglobin A1c and mental health outcomes.

    View details for DOI 10.2196/46050

    View details for PubMedID 37535407

  • Swimming With the Omnipod 5 Automated Insulin Delivery System: Connectivity in the Water. Diabetes care Hughes, M. S., Kingman, R. S., Hsu, L., Lal, R. A., Buckingham, B. A., Zaharieva, D. P. 2023

    View details for DOI 10.2337/dc23-0470

    View details for PubMedID 37311429

  • Spectro-spatial features in distributed human intracranial activity proactively encode peripheral metabolic activity. Nature communications Huang, Y., Wang, J. B., Parker, J. J., Shivacharan, R., Lal, R. A., Halpern, C. H. 2023; 14 (1): 2729


    Mounting evidence demonstrates that the central nervous system (CNS) orchestrates glucose homeostasis by sensing glucose and modulating peripheral metabolism. Glucose responsive neuronal populations have been identified in the hypothalamus and several corticolimbic regions. However, how these CNS gluco-regulatory regions modulate peripheral glucose levels is not well understood. To better understand this process, we simultaneously measured interstitial glucose concentrations and local field potentials in 3 human subjects from cortical and subcortical regions, including the hypothalamus in one subject. Correlations between high frequency activity (HFA, 70-170 Hz) and peripheral glucose levels are found across multiple brain regions, notably in the hypothalamus, with correlation magnitude modulated by sleep-wake cycles, circadian coupling, and hypothalamic connectivity. Correlations are further present between non-circadian (ultradian) HFA and glucose levels which are higher during awake periods. Spectro-spatial features of neural activity enable decoding of peripheral glucose levels both in the present and up to hours in the future. Our findings demonstrate proactive encoding of homeostatic glucose dynamics by the CNS.

    View details for DOI 10.1038/s41467-023-38253-7

    View details for PubMedID 37169738

    View details for PubMedCentralID PMC10174612

  • Practical Aspects and Exercise Safety Benefits of Automated Insulin Delivery Systems in Type 1 Diabetes. Diabetes spectrum : a publication of the American Diabetes Association Zaharieva, D. P., Morrison, D., Paldus, B., Lal, R. A., Buckingham, B. A., O'Neal, D. N. 2023; 36 (2): 127-136


    Regular exercise is essential to overall cardiovascular health and well-being in people with type 1 diabetes, but exercise can also lead to increased glycemic disturbances. Automated insulin delivery (AID) technology has been shown to modestly improve glycemic time in range (TIR) in adults with type 1 diabetes and significantly improve TIR in youth with type 1 diabetes. Available AID systems still require some user-initiated changes to the settings and, in some cases, significant pre-planning for exercise. Many exercise recommendations for type 1 diabetes were developed initially for people using multiple daily insulin injections or insulin pump therapy. This article highlights recommendations and practical strategies for using AID around exercise in type 1 diabetes.

    View details for DOI 10.2337/dsi22-0018

    View details for PubMedID 37193203

    View details for PubMedCentralID PMC10182962

  • The First Regulatory Clearance of an Open-Source Automated Insulin Delivery Algorithm. Journal of diabetes science and technology Braune, K., Hussain, S., Lal, R. 2023: 19322968231164166


    Open-source Automated Insulin Dosing (OS-AID) algorithms are made publicly accessible so that every facet of their operation can be understood. Currently, commercial AID algorithms are kept proprietary trade secrets, despite the role they take in making life and death decisions for people living with type 1 diabetes. Loop was the second OS-AID algorithm, developed initially by Nate Racklyeft and Pete Schwamb. In 2018, the nonprofit organization Tidepool (Palo Alto, CA) announced the launch of the "Tidepool Loop" initiative with the aim to generate real-world evidence and obtain regulatory clearance. By the end of 2020, the U.S. Food and Drug Administration received Tidepool's application for an interoperable automated glycemic controller based on Loop. After 2 years, the FDA approved the Tidepool Loop on January 23, 2023.

    View details for DOI 10.1177/19322968231164166

    View details for PubMedID 37051947

  • Frequency and detection of insulin infusion site failure in the Type 1 Diabetes Exchange Online Community. Diabetes technology & therapeutics Hughes, M. S., Douvas, J. L., Layfield-Bryan, M., Blanco, L. E., Gray, J. C., Zapotoczny, G., Espinoza, J., Wilcox, J. H., Lal, R. A. 2023


    Insulin infusion site (IIS) failures are a weakness in insulin pump therapy. We examined experience with IIS failures among US individuals with diabetes on insulin pump via survey distributed to the T1D Exchange Online Community. Demographic factors, IIS characteristics, and diabetes-related perceptions were assessed by logistic regression to determine odds of higher (≥1 per month) or lower (<1 per month) reported IIS failure frequency. IIS failures were common; 41.4% reported ≥1 per month. IIS failure is usually detected through development of hyperglycemia rather than pump alarm. No assessed demographic factor or IIS characteristic was predictive; however, higher odds of ≥1 failure per month was associated with feelings of burnout (OR 1.489 [1.024, 2.165]) and considering pump discontinuation (OR 2.233 [1.455, 3.427]). IIS failures are frequent and unpredictable, typically require hyperglycemia for detection, and are associated with negative perceptions. More should be done toward preventing IIS failures and/or detecting them sooner.

    View details for DOI 10.1089/dia.2023.0005

    View details for PubMedID 36856574

  • Insulin Delivery Hardware: Pumps and Pens. Diabetes technology & therapeutics Lal, R. A., Leelarathna, L. 2023; 25 (S1): S30-S43

    View details for DOI 10.1089/dia.2023.2503

    View details for PubMedID 36802186

  • Diabetes Technology Meeting 2022. Journal of diabetes science and technology Huang, J., Yeung, A. M., DuBord, A. Y., Wolpert, H., Jacobs, P. G., Lee, W. A., Drincic, A., Spanakis, E. K., Sherr, J. L., Prahalad, P., Fleming, A., Hsiao, V. C., Kompala, T., Lal, R. A., Fayfman, M., Ginsberg, B. H., Galindo, R. J., Stuhr, A., Chase, J. G., Najafi, B., Masharani, U., Seley, J. J., Klonoff, D. C. 2023: 19322968221148743


    Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 3 to November 5, 2022. Meeting topics included (1) the measurement of glucose, insulin, and ketones; (2) virtual diabetes care; (3) metrics for managing diabetes and predicting outcomes; (4) integration of continuous glucose monitor data into the electronic health record; (5) regulation of diabetes technology; (6) digital health to nudge behavior; (7) estimating carbohydrates; (8) fully automated insulin delivery systems; (9) hypoglycemia; (10) novel insulins; (11) insulin delivery; (12) on-body sensors; (13) continuous glucose monitoring; (14) diabetic foot ulcers; (15) the environmental impact of diabetes technology; and (16) spinal cord stimulation for painful diabetic neuropathy. A live demonstration of a device that can allow for the recycling of used insulin pens was also presented.

    View details for DOI 10.1177/19322968221148743

    View details for PubMedID 36704821

  • Project ECHO Diabetes Cost Modeling to Support the Replication and Expansion of Tele-mentoring Programs in Non-research Settings. Diabetes therapy : research, treatment and education of diabetes and related disorders Lewit, E. M., Figg, L. E., Addala, A., Filipp, S. L., Lal, R., Gurka, M. J., Herndon, J. B., Haller, M. J., Maahs, D. M., Walker, A. F. 2023


    Project ECHO Diabetes is a tele-education learning model for primary care providers (PCPs) seeking to improve care for patients with diabetes from marginalized communities. Project ECHO Diabetes utilized expert "hub" teams comprising endocrinologists, dieticians, nurses, psychologists, and social workers and "spokes" consisting of PCPs and their patients with diabetes. This Project ECHO Diabetes model provided diabetes support coaches to provide additional support to patients. We sought to estimate the costs of operating a Project ECHO Diabetes hub, inclusive of diabetes support coach costs.Data from Project ECHO Diabetes from June 2021 to June 2022 and wages from national databases were used to estimate hub and diabetes support coach costs to operate a 6-month, 24-session Project ECHO Diabetes program at hubs (University of Florida and Stanford University) and spokes (PCP clinic sites in Florida and California).Hub costs for delivering a 6-month Project ECHO Diabetes program to five spoke clinics were $96,873. Personnel costs were the principal driver. Mean cost was $19,673 per spoke clinic and $11.37 per spoke clinic patient. Diabetes support coach costs were estimated per spoke clinic and considered scalable in that they would increase proportionately with the number of spoke clinics in a Project ECHO Diabetes cohort. Mean diabetes support coach costs were $6,506 per spoke clinic and $3.72 per patient. Total program costs per hub were $129,404. Mean cost per clinic was $25,881. Mean cost per patient was $15.03.Herein, we document real-world costs to operate a Project ECHO Diabetes hub and diabetes support coaches. Future analysis of Project ECHO Diabetes will include estimates of spoke participation costs and changes in health care costs and savings. As state agencies, insurers, and philanthropies consider the replication of Project ECHO Diabetes, this analysis provides important initial information regarding primary operating costs.

    View details for DOI 10.1007/s13300-022-01364-3

    View details for PubMedID 36680682

  • Open-source automated insulin delivery in type 1 diabetes-the evidence is out there. The lancet. Diabetes & endocrinology Hussain, S., Lal, R. A., Braune, K. 2022

    View details for DOI 10.1016/S2213-8587(22)00283-2

    View details for PubMedID 36244346

  • Appropriate Use of Telehealth Visits in Endocrinology: Policy Perspective of the Endocrine Society. The Journal of clinical endocrinology and metabolism Vimalananda, V. G., Brito, J. P., Eiland, L. A., Lal, R. A., Maraka, S., McDonnell, M. E., Narla, R. R., Roth, M. Y., Crossen, S. S. 2022


    OBJECTIVE: This work aims to guide clinicians practicing endocrinology in the use of telehealth (synchronous patient-clinician visits conducted over video or telephone) for outpatient care.PARTICIPANTS: The Endocrine Society convened a 9-member panel of US endocrinologists with expertise in telehealth clinical care, telehealth operations, patient-centered care, health care delivery research, and/or evidence-based medicine.EVIDENCE: The panel conducted a literature search to identify studies published since 2000 about telehealth in endocrinology. One member extracted a list of factors affecting the quality of endocrine care via telehealth from the extant literature. The panel grouped these factors into 5 domains: clinical, patient, patient-clinician relationship, clinician, and health care setting and technology.CONSENSUS PROCESS: For each domain, 2 or 3 members drew on existing literature and their expert opinions to draft a section examining the effect of the domain's component factors on the appropriateness of telehealth use within endocrine practice. Appropriateness was evaluated in the context of the 6 Institute of Medicine aims for health care quality: patient-centeredness, equity, safety, effectiveness, timeliness, and efficiency. The panel held monthly virtual meetings to discuss and revise each domain. Two members wrote the remaining sections and integrated them with the domains to create the full policy perspective, which was reviewed and revised by all members.CONCLUSIONS: Telehealth has become a common care modality within endocrinology. This policy perspective summarizes the factors determining telehealth appropriateness in various patient care scenarios. Strategies to increase the quality of telehealth care are offered. More research is needed to develop a robust evidence base for future guideline development.

    View details for DOI 10.1210/clinem/dgac494

    View details for PubMedID 36194041

  • Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes. The New England journal of medicine Russell, S. J., Beck, R. W., Damiano, E. R., El-Khatib, F. H., Ruedy, K. J., Balliro, C. A., Li, Z., Calhoun, P., Wadwa, R. P., Buckingham, B., Zhou, K., Daniels, M., Raskin, P., White, P. C., Lynch, J., Pettus, J., Hirsch, I. B., Goland, R., Buse, J. B., Kruger, D., Mauras, N., Muir, A., McGill, J. B., Cogen, F., Weissberg-Benchell, J., Sherwood, J. S., Castellanos, L. E., Hillard, M. A., Tuffaha, M., Putman, M. S., Sands, M. Y., Forlenza, G., Slover, R., Messer, L. H., Cobry, E., Shah, V. N., Polsky, S., Lal, R., Ekhlaspour, L., Hughes, M. S., Basina, M., Hatipoglu, B., Olansky, L., Bhangoo, A., Forghani, N., Kashmiri, H., Sutton, F., Choudhary, A., Penn, J., Jafri, R., Rayas, M., Escaname, E., Kerr, C., Favela-Prezas, R., Boeder, S., Trikudanathan, S., Williams, K. M., Leibel, N., Kirkman, M. S., Bergamo, K., Klein, K. R., Dostou, J. M., Machineni, S., Young, L. A., Diner, J. C., Bhan, A., Jones, J. K., Benson, M., Bird, K., Englert, K., Permuy, J., Cossen, K., Felner, E., Salam, M., Silverstein, J. M., Adamson, S., Cedeno, A., Meighan, S., Dauber, A. 2022; 387 (13): 1161-1172


    Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed.A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group.In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; number, NCT04200313.).

    View details for DOI 10.1056/NEJMoa2205225

    View details for PubMedID 36170500

  • Consensus Recommendations for the Use of Automated Insulin Delivery (AID) Technologies in Clinical Practice. Endocrine reviews Phillip, M., Nimri, R., Bergenstal, R. M., Barnard-Kelly, K., Danne, T., Hovorka, R., Kovatchev, B. P., Messer, L. H., Parkin, C. G., Ambler-Osborn, L., Amiel, S. A., Bally, L., Beck, R. W., Biester, S., Biester, T., Blanchette, J. E., Bosi, E., Boughton, C. K., Breton, M. D., Brown, S. A., Buckingham, B. A., Cai, A., Carlson, A. L., Castle, J. R., Choudhary, P., Close, K. L., Cobelli, C., Criego, A. B., Davis, E., de Beaufort, C., de Bock, M. I., DeSalvo, D. J., DeVries, J. H., Dovc, K., Doyle, F. J., Ekhlaspour, L., Shvalb, N. F., Forlenza, G. P., Gallen, G., Garg, S. K., Gershenoff, D. C., Gonder-Frederick, L. A., Haidar, A., Hartnell, S., Heinemann, L., Heller, S., Hirsch, I. B., Hood, K. K., Isaacs, D., Klonoff, D. C., Kordonouri, O., Kowalski, A., Laffel, L., Lawton, J., Lal, R. A., Leelarathna, L., Maahs, D. M., Murphy, H. R., Norgaard, K., O'Neal, D., Oser, S., Oser, T., Renard, E., Riddell, M. C., Rodbard, D., Russell, S. J., Schatz, D. A., Shah, V. N., Sherr, J. L., Simonson, G. D., Wadwa, R. P., Ward, C., Weinzimer, S. A., Wilmot, E. G., Battelino, T. 2022


    The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past six years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage.

    View details for DOI 10.1210/endrev/bnac022

    View details for PubMedID 36066457

  • Temporal changes in hemoglobin A1c and diabetes technology use in DPV, NPDA and T1DX pediatric cohorts from 2010 to 2018. Diabetes technology & therapeutics Lal, R. A., Robinson, H., Lanzinger, S., Miller, K., Perez, S. P., Kovacic, R., Calhoun, P., Campbell, F., Naeke, A., Maahs, D. M., Holl, R. W., Warner, J. 2022


    Objective The German/Austrian Diabetes Patient Follow-up Registry (DPV), England/Wales National Pediatric Diabetes Audit (NPDA), and Type 1 Diabetes Exchange (T1DX) in the U.S. investigated changes in hemoglobin A1c (HbA1c) and diabetes technology use from 2010-2018. Methods Registry/audit data from 2010-2018 were analyzed in annual cohorts using linear regression for those <18 years of age with type 1 diabetes diagnosed at age >6 months. Time trends in HbA1c, pump, and CGM use were studied using repeated measurements linear and logistic regression models with an autoregressive covariance structure and with year and data source as independent variables. Results 1,172,980 visits among 114,264 (54,119 DPV, 43,550 NPDA, 16,595 T1DX) patients were identified. HbA1c remained clinically stable in DPV (7.7%[61mmol/mol] to 7.6%[60mmol/mol]), decreased in the NPDA (8.7%[72mmol/mol] to 7.9%[63mmol/mol]), and increased in T1DX (8.0%[64mmol/mol] to 8.5%[69mmol/mol] from 2010 to 2018). In all registries/audits, insulin pump and CGM use increased over time with greatest pump use in T1DX and lowest uptake reported in NPDA. Conclusions These data reveal three different longitudinal patterns of change in registry/audit HbA1c from 2010-2018. Diabetes technology use increased throughout, at different rates. Quality improvement (QI) programs in DPV have been ongoing for 25 years, began in NPDA 2009, and T1DX in 2016. We speculate that in England/Wales development of networks, peer-review, and implementation of QI measures contributed to reductions in population HbA1c. Many of these interventions had been implemented in DPV prior to 2010. Further efforts to understand this improvement, including the role of QI, and continued success within standardized documentation and benchmarking could inform T1DX programs to reduce HbA1c.

    View details for DOI 10.1089/dia.2022.0095

    View details for PubMedID 35856740

  • Psychosocial Effects of the Loop Open-Source Automated Insulin Delivery System. Journal of diabetes science and technology Wong, J. J., Hood, K. K., Hanes, S. J., Lal, R. A., Naranjo, D. 2022: 19322968221105288


    This study examined the psychosocial impact of Loop, an open-source automated insulin dosing system that has emerged from the diabetes technology "Do-It-Yourself" (DIY) movement.Subsamples of 239 adults, 115 children, and 243 parents completed data collection at the time of Loop initiation and 3 and 6 months later. Surveys collected demographic and clinical information, percent time-in-range, HbA1c, and validated psychosocial measures. Analyses included paired t tests and McNemar's tests to compare psychosocial functioning at 3 and 6 months and regression models to assess baseline predictors of psychosocial outcomes at 6 months.Adults reported significant improvements in diabetes distress (t = -7.20 P < .001; t = -8.01, P < .001), sleep quality (t = 6.81, P < .001; t = 2.98, P = .003), fear of hypoglycemia (t = -4.42, P < .001; t = -4.97, P < .001), and hypoglycemia confidence (t = 8.68, P < .001; t = 7.96 P < .001) from baseline to 3 months and 6 months, respectively. Significant improvements in parents' and children's sleep quality and parents' fear of hypoglycemia were also observed. Several baseline characteristics were associated with psychosocial outcomes at 6 months.The current findings support the broad and sustained benefits of Loop across multiple aspects of psychosocial well-being. Advancement and dissemination of such technologies has the potential to improve mental and physiological health among people living with type 1 diabetes.

    View details for DOI 10.1177/19322968221105288

    View details for PubMedID 35771004

  • Smartwatch Gesture-Based Meal Reminders Improve Glycemic Control. Diabetes, obesity & metabolism Corbett, J. P., Hsu, L., Brown, S. A., Kollar, L., Vleugels, K., Buckingham, B., Breton, M. D., Lal, R. A. 2022

    View details for DOI 10.1111/dom.14737

    View details for PubMedID 35491517

  • A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings. Journal of diabetes science and technology Klonoff, D. C., Wang, J., Rodbard, D., Kohn, M. A., Li, C., Liepmann, D., Kerr, D., Ahn, D., Peters, A. L., Umpierrez, G. E., Seley, J. J., Xu, N. Y., Nguyen, K. T., Simonson, G., Agus, M. S., Al-Sofiani, M. E., Armaiz-Pena, G., Bailey, T. S., Basu, A., Battelino, T., Bekele, S. Y., Benhamou, P., Bequette, B. W., Blevins, T., Breton, M. D., Castle, J. R., Chase, J. G., Chen, K. Y., Choudhary, P., Clements, M. A., Close, K. L., Cook, C. B., Danne, T., Doyle, F. J., Drincic, A., Dungan, K. M., Edelman, S. V., Ejskjaer, N., Espinoza, J. C., Fleming, G. A., Forlenza, G. P., Freckmann, G., Galindo, R. J., Gomez, A. M., Gutow, H. A., Heinemann, L., Hirsch, I. B., Hoang, T. D., Hovorka, R., Jendle, J. H., Ji, L., Joshi, S. R., Joubert, M., Koliwad, S. K., Lal, R. A., Lansang, M. C., Lee, W. A., Leelarathna, L., Leiter, L. A., Lind, M., Litchman, M. L., Mader, J. K., Mahoney, K. M., Mankovsky, B., Masharani, U., Mathioudakis, N. N., Mayorov, A., Messler, J., Miller, J. D., Mohan, V., Nichols, J. H., Norgaard, K., O'Neal, D. N., Pasquel, F. J., Philis-Tsimikas, A., Pieber, T., Phillip, M., Polonsky, W. H., Pop-Busui, R., Rayman, G., Rhee, E., Russell, S. J., Shah, V. N., Sherr, J. L., Sode, K., Spanakis, E. K., Wake, D. J., Waki, K., Wallia, A., Weinberg, M. E., Wolpert, H., Wright, E. E., Zilbermint, M., Kovatchev, B. 2022: 19322968221085273


    BACKGROUND: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.METHODS: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.RESULTS: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.CONCLUSION: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

    View details for DOI 10.1177/19322968221085273

    View details for PubMedID 35348391

  • Insulin Delivery Hardware: Pumps and Pens. Diabetes technology & therapeutics Lal, R., Leelarathna, L. 2022; 24 (S1): S21-S34

    View details for DOI 10.1089/dia.2022.2502

    View details for PubMedID 35475688

  • Current Status and Emerging Options for Automated Insulin Delivery Systems. Diabetes technology & therapeutics Forlenza, G. P., Lal, R. A. 1800


    Combining technologies including rapid insulin analogs, insulin pumps, continuous glucose monitors (CGMs), and control algorithms has allowed for the creation of automated insulin delivery (AID) systems. These systems have proven to be the most effective technology for optimizing metabolic control and could hold the key to broadly achieving goal-level glycemic control for people with type 1 diabetes (T1D). The use of AID has exploded in the past several years with several options available in the United States and even more in Europe. In this article, we review the largest studies involving these AID systems, and then examine future directions for AID with an emphasis on usability.

    View details for DOI 10.1089/dia.2021.0514

    View details for PubMedID 35099302

  • Qualitative Study of User Experiences with Loop, an Open-Source Automated Insulin Delivery (AID) System. Diabetes technology & therapeutics Suttiratana, S., Wong, J., Lanning, M. S., Dunlap, A. R., Hanes, S., Hood, K., Lal, R. A., Naranjo, D. 1800


    BACKGROUND: Loop is an open-source automated insulin delivery (AID) system, used by more than 9,000 people with Type 1 diabetes. Understanding the pros and cons of Loop use may help improve disease management and support population level innovation.METHODS: Focus groups revealed 72 new and existing users' perspectives on Loop uptake, use and persistence. A subsample of participants from a mixed methods observational cohort study shared first-hand accounts of their experiences using Loop. Participants were predominately white (95%), male (50%), privately insured (94%), reported annual household income ≥ $100K (73%) and education exceeding a bachelor's degree (87%) with a mean HbA1c of 6.6±0.8%. Data were analyzed and synthesized by a multidisciplinary team.RESULTS: Participants detailed their experiences with a) Loop technical support and troubleshooting, b) decreased mental/behavioral burden, c) technical issues with parts of the system, d) glycemic control, e) personalizing settings, and f) providers while using Loop. Decreased burden was the most endorsed benefit defined by less worry, stress, and cognitive effort and less time spent on diabetes management tasks. Participants highlighted the benefits of Loop overnight and their introduction to "Loop communities" during use. The most discussed challenges involved technical issues. A range of provider attitudes and knowledge about Loop complicated users' clinical experiences and disclosure.CONCLUSIONS: This sample of new and experienced Loop users reported benefits to quality of life and glycemic control that outweighed challenges of setting up system components, customizing the system to suit one's lifestyle and habits, and adjusting system settings. Challenges related to system set up and calibrating settings are remediable and, if addressed, may better serve Loop users. Users reported feeling empowered by the customizability of and the educational effects facilitated by the open source AID system. Loop helped users learn more about their chronic illness and physiology in an acceptable format.

    View details for DOI 10.1089/dia.2021.0485

    View details for PubMedID 35099278

  • Tele-education model for primary care providers to advance diabetes equity: Findings from Project ECHO Diabetes. Frontiers in endocrinology Addala, A., Filipp, S. L., Figg, L. E., Anez-Zabala, C., Lal, R. A., Gurka, M. J., Haller, M. J., Maahs, D. M., Walker, A. F., Project ECHO Diabetes Research Team, Haller, M., Sheehan, E., Bernier, A., Westen, S., Stahmer, H., Donahoo, W. T., Roque, X., Malden, G., Hechavarria, M., Maahs, D., Lal, R., Addala, A., Figg, L., Yabut, K., Alramahi, N., Cortes, A., Zaharieva, D., Basina, M., Judge, K., Wilke, L., Hood, K., Wong, J., Wang, J., Bhatia, S., Lewit, E. 2022; 13: 1066521


    Introduction: In the US, many individuals with diabetes do not have consistent access to endocrinologists and therefore rely on primary care providers (PCPs) for their diabetes management. Project ECHO (Extension for Community Healthcare Outcomes) Diabetes, a tele-education model, was developed to empower PCPs to independently manage diabetes, including education on diabetes technology initiation and use, to bridge disparities in diabetes.Methods: PCPs (n=116) who participated in Project ECHO Diabetes and completed pre- and post-intervention surveys were included in this analysis. The survey was administered in California and Florida to participating PCPs via REDCap and paper surveys. This survey aimed to evaluate practice demographics, protocols with adult and pediatric T1D management, challenges, resources, and provider knowledge and confidence in diabetes management. Differences and statistical significance in pre- and post-intervention responses were evaluated via McNemar's tests.Results: PCPs reported improvement in all domains of diabetes education and management. From baseline, PCPs reported improvement in their confidence to serve as the T1D provider for their community (pre vs post: 43.8% vs 68.8%, p=0.005), manage insulin therapy (pre vs post: 62.8% vs 84.3%, p=0.002), and identify symptoms of diabetes distress (pre vs post: 62.8% vs 84.3%, p=0.002) post-intervention. Compared to pre-intervention, providers reported significant improvement in their confidence in all aspects of diabetes technology including prescribing technology (41.2% vs 68.6%, p=0.001), managing insulin pumps (41.2% vs 68.6%, p=0.001) and hybrid closed loop (10.2% vs 26.5%, p=0.033), and interpreting sensor data (41.2% vs 68.6%, p=0.001) post-intervention.Discussion: PCPs who participated in Project ECHO Diabetes reported increased confidence in diabetes management, with notable improvement in their ability to prescribe, manage, and troubleshoot diabetes technology. These data support the use of tele-education of PCPs to increase confidence in diabetes technology management as a feasible strategy to advance equity in diabetes management and outcomes.

    View details for DOI 10.3389/fendo.2022.1066521

    View details for PubMedID 36589850

  • Using Peer Power to Reduce Health Disparities: Implementation of a Diabetes Support Coach Program in Federally Qualified Health Centers. Diabetes spectrum : a publication of the American Diabetes Association Walker, A. F., Addala, A., Sheehan, E., Lal, R., Haller, M., Cuttriss, N., Filipp, S., Baer, L., Gurka, M., Bernier, A., Figg, L., Westen, S., Hood, K., Anez-Zabala, C., Frank, E., Roque, X., Maizel, J., Maahs, D. 2022; 35 (3): 295-303


    Community health workers (CHWs) provide vital support to underserved communities in the promotion of health equity by addressing barriers related to the social determinants of health that often prevent people living with diabetes from achieving optimal health outcomes. Peer support programs in diabetes can also offer people living with diabetes invaluable support through a shared understanding of the disease and by offsetting diabetes-related stigma. As part of a Project Extension for Community Healthcare Outcomes (ECHO) Diabetes program, participating federally qualified healthcare centers were provided diabetes support coaches (DSCs) to facilitate patient engagement. DSCs hold invaluable expert knowledge, as they live with diabetes themselves and reside in areas they serve, thus combining the CHW role with peer support models. The use of DSCs and CHWs during the coronavirus disease 2019 pandemic and beyond is highly effective at reaching underserved communities with diabetes and promoting health equity.

    View details for DOI 10.2337/dsi22-0004

    View details for PubMedID 36082018

  • Novel Pathogenic de novo INS p.T97P Variant Presenting with Severe Neonatal DKA. Endocrinology Lal, R. A., Moeller, H. P., Thomson, E. A., Horton, T. M., Lee, S., Freeman, R., Prahalad, P., Poon, A. S., Annes, J. P. 2021


    Pathogenic INS gene mutations are causative for Mutant INS-gene-induced Diabetes of Youth (MIDY). We characterize a novel de novo heterozygous INS gene mutation (c.289A>C, p.T97P) that presented in an autoantibody-negative 5-month-old male infant with severe diabetic ketoacidosis. In silico pathogenicity prediction tools provided contradictory interpretations, while structural modeling indicated a deleterious effect on proinsulin folding. Transfection of wildtype and INS p.T97P expression and luciferase reporter constructs demonstrated elevated intracellular mutant proinsulin levels and dramatically impaired proinsulin/insulin and luciferase secretion. Notably, proteasome inhibition partially and selectively rescued INS p.T97P-derived luciferase secretion. Additionally, expression of INS p.T97P caused increased intracellular proinsulin aggregate formation and XBP-1s protein levels, consistent with induction of endoplasmic reticulum stress. We conclude that INS p.T97P is a newly identified pathogenic A-chain variant that is causative for MIDY via disruption of proinsulin folding and processing with induction of the endoplasmic reticulum stress response.

    View details for DOI 10.1210/endocr/bqab246

    View details for PubMedID 34888628

  • Open-source automated insulin delivery: international consensus statement and practical guidance for health-care professionals. The lancet. Diabetes & endocrinology Braune, K., Lal, R. A., Petruzelkova, L., Scheiner, G., Winterdijk, P., Schmidt, S., Raimond, L., Hood, K. K., Riddell, M. C., Skinner, T. C., Raile, K., Hussain, S., OPEN International Healthcare Professional Network and OPEN Legal Advisory Group 2021


    Open-source automated insulin delivery systems, commonly referred to as do-it-yourself automated insulin delivery systems, are examples of user-driven innovation that was co-created and supported by an online community who were directly affected by diabetes. Their uptake continues to increase globally, with current estimates suggesting several thousand active users worldwide. Real-world user-driven evidence is growing and provides insights into safety and effectiveness of these systems. The aim of this consensus statement is two-fold. Firstly, it provides a review of the current evidence, description of the technologies, and discusses the ethics and legal considerations for these systems from an international perspective. Secondly, it provides a much-needed international health-care consensus supporting the implementation of open-source systems in clinical settings, with detailed clinical guidance. This consensus also provides important recommendations for key stakeholders that are involved in diabetes technologies, including developers, regulators, and industry, and provides medico-legal and ethical support for patient-driven, open-source innovations.

    View details for DOI 10.1016/S2213-8587(21)00267-9

    View details for PubMedID 34785000

  • Automated Insulin Dosing Systems: Advances After a Century of Insulin. Diabetic medicine : a journal of the British Diabetic Association Thabit, H., Lal, R., Leelarathna, L. 2021: e14695


    The daily complexities of insulin therapy and glucose variability in type 1 diabetes still pose significant challenges, despite advancements in modern insulin analogues. Minimising hypoglycaemia and optimising time spent within target glucose range are recommended to reduce the risk of diabetes-related complications and distress. Access to structured education and adjuvant diabetes technologies such as insulin pumps and glucose sensors, are recommended by National Institute for Health and Care Excellence (NICE) to enable people with type 1 diabetes achieve their glycaemic goals. One hundred years after the discovery of insulin, automated insulin dosing (AID, a.k.a. closed-loop or artificial pancreas) systems are a reality with a number of systems available and being used in usual clinical practice. Evidence from randomised clinical trials and real-world prospective studies support efficacy, effectiveness and safety of AID systems. Qualitative evaluations reveal treatment satisfaction and positive effects on quality-of-life. Current insulin-only AID systems still require carbohydrate and activity announcement (hybrid closed-loop) due to the inherent pharmacokinetic limitations of rapid-acting insulin analogies. Ultra-rapid acting insulin, and adjunctive use of other therapies (e.g. glucagon, pramlitide) are being evaluated to achieve full closed-loop. Open-source AID (OS-AID) systems have been developed by the diabetes community, driven by a desire for safety and to accelerate technological advancement. In addition to effectiveness and safety, real-world prospective studies suggest that OS-AID systems fulfill unmet needs of commercially approved systems. The development, ongoing challenges and expectations of AID are outlined in this review.

    View details for DOI 10.1111/dme.14695

    View details for PubMedID 34547133

  • Ultra-Fast Insulin-Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Maikawa, C. L., Chen, P. C., Vuong, E. T., Nguyen, L. T., Mann, J. L., d'Aquino, A. I., Lal, R. A., Maahs, D. M., Buckingham, B. A., Appel, E. A. 2021: e2101575


    Dual-hormone replacement therapy with insulin and amylin in patients with type 1 diabetes has the potential to improve glucose management. Unfortunately, currently available formulations require burdensome separate injections at mealtimes and have disparate pharmacokinetics that do not mimic endogenous co-secretion. Here, amphiphilic acrylamide copolymers are used to create a stable co-formulation of monomeric insulin and amylin analogues (lispro and pramlintide) with synchronous pharmacokinetics and ultra-rapid action. The co-formulation is stable for over 16 h under stressed aging conditions, whereas commercial insulin lispro (Humalog) aggregates in 8 h. The faster pharmacokinetics of monomeric insulin in this co-formulation result in increased insulin-pramlintide overlap of 75 ± 6% compared to only 47 ± 7% for separate injections. The co-formulation results in similar delay in gastric emptying compared to pramlintide delivered separately. In a glucose challenge, in rats, the co-formulation reduces deviation from baseline glucose compared to insulin only, or separate insulin and pramlintide administrations. Further, comparison of interspecies pharmacokinetics of monomeric pramlintide suggests that pharmacokinetics observed for the co-formulation will be well preserved in future translation to humans. Together these results suggest that the co-formulation has the potential to improve mealtime glucose management and reduce patient burden in the treatment of diabetes.

    View details for DOI 10.1002/advs.202101575

    View details for PubMedID 34499434

  • Democratizing type 1 diabetes specialty care in the primary care setting to reduce health disparities: project extension for community healthcare outcomes (ECHO) T1D. BMJ open diabetes research & care Walker, A. F., Cuttriss, N., Haller, M. J., Hood, K. K., Gurka, M. J., Filipp, S. L., Anez-Zabala, C., Yabut, K., Roque, X., Wong, J. J., Baer, L., Figg, L., Bernier, A., Westen, S., Lewit, E., Sheehan, E., Basina, M., Lal, R., Maizel, J., Maahs, D. M. 2021; 9 (1)


    INTRODUCTION: Project ECHO (Extension for Community Healthcare Outcomes) is a tele-education outreach model that seeks to democratize specialty knowledge to reduce disparities and improve health outcomes. Limited utilization of endocrinologists forces many primary care providers (PCPs) to care for patients with type 1 diabetes (T1D) without specialty support. Accordingly, an ECHO T1D program was developed and piloted in Florida and California. Our goal was to demonstrate the feasibility of an ECHO program focused on T1D and improve PCPs' abilities to manage patients with T1D.RESEARCH DESIGN AND METHODS: Health centers (ie, spokes) were recruited into the ECHO T1D pilot through an innovative approach, focusing on Federally Qualified Health Centers and through identification of high-need catchment areas using the Neighborhood Deprivation Index and provider geocoding. Participating spokes received weekly tele-education provided by the University of Florida and Stanford University hub specialty team through virtual ECHO clinics, real-time support with complex T1D medical decision-making, access to a diabetes support coach, and access to an online repository of diabetes care resources. Participating PCPs completed pre/post-tests assessing diabetes knowledge and confidence and an exit survey gleaning feedback about overall ECHO T1D program experiences.RESULTS: In Florida, 12 spoke sites enrolled with 67 clinics serving >1000 patients with T1D. In California, 11 spoke sites enrolled with 37 clinics serving >900 patients with T1D. During the 6-month intervention, 27 tele-education clinics were offered and n=70 PCPs (22 from Florida, 48 from California) from participating spoke sites completed pre/post-test surveys assessing diabetes care knowledge and confidence in diabetes care. There was statistically significant improvement in diabetes knowledge (p≤0.01) as well as in diabetes confidence (p≤0.01).CONCLUSIONS: The ECHO T1D pilot demonstrated proof of concept for a T1D-specific ECHO program and represents a viable model to reach medically underserved communities which do not use specialists.

    View details for DOI 10.1136/bmjdrc-2021-002262

    View details for PubMedID 34244218

  • Insulin Delivery Hardware: Pumps and Pens. Diabetes technology & therapeutics Lal, R. A., Leelarathna, L. 2021; 23 (S2): S32-S45

    View details for DOI 10.1089/dia.2021.2503

    View details for PubMedID 34061635

  • Longevity of the Novel ConvaTec Infusion Set with Lantern Technology. Diabetes, obesity & metabolism Lal, R. A., Hsu, L., Zhang, J., Schondorff, P. K., Heschel, M., Buckingham, B. 2021


    Current insulin infusion sets are approved for only 2-3days. The novel ConvaTec infusion set with Lantern Technology is designed to extend infusion set wear time. The goal of this pilot study was to evaluate duration of wear for this set. This was a pilot safety study in adults with type 1 diabetes using tethered insulin pumps. Participants inserted the set and wore it for 10days or until failure. Among 24 participants, 2 were excluded. 45% of the sets lasted 10days. Median wear time was 9.1 (7.1,10.0) days. Among 12 premature failures: 6 (50%) involved adhesive failures, 4 (33%) hyperglycemia unresponsive to correction, 1 (8%) hyperglycemia with ketones and 1 (8%) infection. Average CGM glucose per day of infusion set wear demonstrated a statistically significant increase over time, while total daily insulin over the same period did not change. In this pilot study the duration of wear for the novel infusion set exceeded previously reported commercial sets (p<0.001). This extended wear technology may eventually allow for a combined glucose sensor and infusion set. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/dom.14395

    View details for PubMedID 33822472

  • Full closed loop open-source algorithm performance comparison in pigs with diabetes. Clinical and translational medicine Lal, R. A., Maikawa, C. L., Lewis, D., Baker, S. W., Smith, A. A., Roth, G. A., Gale, E. C., Stapleton, L. M., Mann, J. L., Yu, A. C., Correa, S., Grosskopf, A. K., Liong, C. S., Meis, C. M., Chan, D., Garner, J. P., Maahs, D. M., Buckingham, B. A., Appel, E. A. 2021; 11 (4): e387


    Understanding how automated insulin delivery (AID) algorithm features impact glucose control under full closed loop delivery represents a critical step toward reducing patient burden by eliminating the need for carbohydrate entries at mealtimes. Here, we use a pig model of diabetes to compare AndroidAPS and Loop open-source AID systems without meal announcements. Overall time-in-range (70-180mg/dl) for AndroidAPS was 58% ± 5%, while time-in-range for Loop was 35% ± 5%. The effect of the algorithms on time-in-range differed between meals and overnight. During the overnight monitoring period, pigs had an average time-in-range of 90% ± 7% when on AndroidAPS compared to 22% ± 8% on Loop. Time-in-hypoglycemia also differed significantly during the lunch meal, whereby pigs running AndroidAPS spent an average of 1.4% (+0.4/-0.8)% in hypoglycemia compared to 10% (+3/-6)% for those using Loop. As algorithm design for closed loop systems continues to develop, the strategies employed in the OpenAPS algorithm (known as oref1) as implemented in AndroidAPS for unannounced meals may result in a better overall control for full closed loop systems.

    View details for DOI 10.1002/ctm2.387

    View details for PubMedID 33931977

  • Feasibility of Spotlight Consultations Tool in Routine Care: Real-World Evidence. Journal of diabetes science and technology Barnard-Kelly, K., Kelly, R. C., Chernavvsky, D., Lal, R., Cohen, L., Ali, A. 2021: 1932296821994088


    BACKGROUND: Burnout in people with diabetes and healthcare professionals (HCPs) is at an all-time high. Spotlight AQ, a novel "smart" adaptive patient questionnaire, is designed to improve consultations by rapidly identifying patient priorities and presenting these in the context of best-practice care pathways to aid consultations. We aimed to determine Spotlight AQ's feasibility in routine care.MATERIALS AND METHODS: The Spotlight prototype tool was trialed at three centers: two UK primary care centers and one US specialist center (June-September 2020). Participants with type 1 (T1D) or type 2 diabetes (T2D) completed the questionnaire prior to their routine consultations. Results were immediately available and formed the basis of the clinical discussion and decision-making within the clinic visit.RESULTS: A convenience sample of 49 adults took part, n=31 T1D, (n=18 female); and n=18 T2D (n=10 male, n=4 female, n=4 gender unreported). Each identified two priority concerns. "Psychological burden of diabetes" was the most common priority concern (T1D n = 27, 87.1%) followed by "gaining more skills about particular aspects of diabetes" (T1D n=19, 61.3%), "improving support around me" (n=8, 25.8%) and "diabetes-related treatment issues" (n=8, 25.8%). Burden of diabetes was widespread as was lack of confidence around self-management. Similarly, psychological burden of diabetes was the primary concern for participants with T2D (n=18,100%) followed by "gaining more skills about aspects of diabetes" (n=7, 38.9%), "improving support around me" (n=7, 38.9%) and "diabetes-related treatment issues" (n=4; 22.2%).CONCLUSIONS: Spotlight AQ is acceptable and feasible for use in routine care. Gaining more skills and addressing the psychological burden of diabetes are high-priority areas that must be addressed to reduce high levels of distress.

    View details for DOI 10.1177/1932296821994088

    View details for PubMedID 33709795

  • Health-Related Quality of Life and Treatment Satisfaction in Parents and Children with Type 1 Diabetes Using Closed-Loop Control. Diabetes technology & therapeutics Cobry, E., Kanapka, L., Cengiz, E., Carria, L., Ekhlaspour, L., Buckingham, B. A., Hood, K., Hsu, L. J., Messer, L., Schoelwer, M., Emory, E., Ruedy, K. J., Beck, R. W., Wadwa, R. P. 2021


    INTRODUCTION: Hybrid closed-loop systems increase time-in-range and reduce glycemic variability. Person-reported outcomes (PROs) are essential to assess the utility of new devices and their impact on quality of life. This manuscript focuses on the PROs for pediatric participants (ages 6-13 yrs) with type 1 diabetes (T1D) and their parents during a trial using the Tandem Control-IQ system, which was shown to increase time-in-range and improve other glycemic metrics.METHODS: One-hundred-one children 6 to 13 years old with T1D were randomly assigned to closed-loop control (CLC) or sensor augmented pump (SAP) in a 16-week randomized clinical trial with extension to 28 weeks during which the SAP group crossed over to CLC. Health-related quality of life and treatment satisfaction measures were obtained from children and their parents at baseline, 16 weeks, and 28 weeks.RESULTS: Neither the children in the CLC group nor their parents had statistically significant changes in PRO outcomes compared with the SAP group at the end of the 16-week RCT and the 28-week extension. Parents in the CLC group reported non-significant improvements in some PRO scores when compared with the SAP group at 16 weeks, which were sustained at 28 weeks. Sleep scores for parents improved from "poor sleep quality" to "adequate sleep quality" between baseline and 16 weeks, however, the change in scores was not statistically different between groups.CONCLUSIONS: Children with T1D who used the Control-IQ system did not experience increased burden compared with those using SAP based on person-reported outcomes from the children and their parents.

    View details for DOI 10.1089/dia.2020.0532

    View details for PubMedID 33404325

  • Predictors of Time-in-Range (70-180 mg/dL) Achieved Using a Closed-Loop Control System. Diabetes technology & therapeutics Schoelwer, M. J., Kanapka, L. G., Wadwa, R. P., Breton, M. D., Ruedy, K. J., Ekhlaspour, L. n., Forlenza, G. P., Cobry, E. C., Messer, L. H., Cengiz, E. n., Jost, E. n., Carria, L. n., Emory, E. n., Hsu, L. J., Weinzimer, S. A., Buckingham, B. A., Lal, R. A., Oliveri, M. C., Kollman, C. C., Dokken, B. B., Cherñavvsky, D. R., Beck, R. W., DeBoer, M. D. 2021


    Background: Studies of closed-loop control (CLC) in patients with type 1 diabetes (T1D) consistently demonstrate improvements in glycemic control as measured by increased time-in-range (TIR) 70-180 mg/dL. However, clinical predictors of TIR in users of CLC systems are needed. Materials and Methods: We analyzed data from 100 children aged 6-13 years with T1D using the Tandem Control-IQ CLC system during a randomized trial or subsequent extension phase. Continuous glucose monitor data were collected at baseline and during 12-16 weeks of CLC use. Participants were stratified into quartiles of TIR on CLC to compare clinical characteristics. Results: TIR for those in the first, second, third, and fourth quartiles was 54%, 65%, 71%, and 78%, respectively. Lower baseline TIR was associated with lower TIR on CLC (r = 0.69, P < 0.001). However, lower baseline TIR was also associated with greater improvement in TIR on CLC (r = -0.81, P < 0.001). During CLC, participants in the highest versus lowest TIR-quartile administered more user-initiated boluses daily (8.5 ± 2.8 vs. 5.8 ± 2.6, P < 0.001) and received fewer automated boluses (3.5 ± 1.0 vs. 6.0 ± 1.6, P < 0.001). Participants in the lowest (vs. the highest) TIR-quartile received more insulin per body weight (1.13 ± 0.27 vs. 0.87 ± 0.20 U/kg/d, P = 0.008). However, in a multivariate model adjusting for baseline TIR, user-initiated boluses and insulin-per-body-weight were no longer significant. Conclusions: Higher baseline TIR is the strongest predictor of TIR on CLC in children with T1D. However, lower baseline TIR is associated with the greatest improvement in TIR. As with open-loop systems, user engagement is important for optimal glycemic control.

    View details for DOI 10.1089/dia.2020.0646

    View details for PubMedID 33689454

  • Discontinued Use of the Loop Insulin Dosing System: A Mixed-Methods Investigation. Diabetes technology & therapeutics Wong, J., Suttiratana, S., Lal, R. A., Lum, J., Lanning, M. S., Dunlap, A., Arbiter, B., Hanes, S., Bailey, R., Hood, K., Naranjo, D. 2021


    Loop is an open-source automated insulin dosing system that allows users unrivaled control over system settings that effect future glucose prediction. Thousands use Loop, but little is known about those who discontinue.In a large observational study, 874 Loop participants completed surveys and provided glycemic data, 46 (5.3%) of those self-identified as discontinuing Loop during the observation window, 45 completed a discontinued use survey, 22 provided system settings data, and 19 participated in semi-structured interviews about their discontinuation. Qualitative data were transcribed, coded, and analyzed.Older age and not trusting Loop were associated with discontinued use, though no other demographic or clinical characteristics were significant correlates. The most endorsed reasons were "I decided to try something else" (27.8%) followed by "It just didn't help as much as I thought it would" (22.2%). Qualitative analyses revealed prominent themes centered upon mental and emotional burden and adjusting settings. Other reasons for discontinued use included: fear of disapproval of Loop use from diabetes provider, barriers to acquiring component devices, a desire to try new/different technologies, concerns that Loop could not accommodate specific exercise or low insulin dose regimens, and worry about Loop use during pregnancy. It was noted that burdens might be alleviated by enhanced technical assistance and expert guidance.While the majority of individuals in the Loop observational study continued use, those who discontinued reported similar challenges. Technical support and education specific to setting calculations could expand Loop benefits, alleviate burden, and support sustained use among new Loop users.

    View details for DOI 10.1089/dia.2021.0362

    View details for PubMedID 34780283

  • Predicting Success with a First-Generation Hybrid Closed Loop Artificial Pancreas System among Children, Adolescents, and Young Adults with Type 1 Diabetes: a Model Development and Validation Study. Diabetes technology & therapeutics Forlenza, G. P., Vigers, T., Berget, C., Messer, L., Lal, R. A., Basina, M., Maahs, D. M., Hood, K., Buckingham, B. A., Wilson, D. M., Wadwa, R. P., Driscoll, K. A., Pyle, L. 2021


    Hybrid Closed Loop (HCL) systems aid individuals with type 1 diabetes in improving glycemic control, however, sustained use over time has not been consistent for all users. This study developed and validated prognostic models for successful 12-month use of the first commercial HCL system based on baseline and 1-month or 3-month data.Data from participants at the Barbara Davis Center (N=85) who began use of the MiniMed 670G HCL were used to develop prognostic models using logistic regression and Lasso model selection. Candidate factors included sex, age, duration of diabetes, baseline HbA1c, race, ethnicity, insurance status, history of insulin pump and continuous glucose monitor use, 1-month or 3-month Auto Mode use, boluses per day, and time in range (70-180 mg/dL; TIR), and scores on behavioral questionnaires. Successful use of HCL was predefined as Auto Mode use ≥60%. The 3-month model was then externally validated against a sample from Stanford University (N=55).Factors in the final model included baseline HbA1c, sex, ethnicity, 1-month or 3-month Auto Mode use, Boluses per Day, and TIR. The 1-month and 3-month prognostic models had very good predictive ability with area under the curve values of 0.894 and 0.900, respectively. External validity was acceptable with an area under the curve of 0.717.Our prognostic models use clinically accessible baseline and early device-use factors to identify risk for failure to succeed with 670G HCL technology. These models may be useful to develop targeted interventions to promote success with new technologies.

    View details for DOI 10.1089/dia.2021.0326

    View details for PubMedID 34780306

  • Engineering biopharmaceutical formulations to improve diabetes management. Science translational medicine Maikawa, C. L., d'Aquino, A. I., Lal, R. A., Buckingham, B. A., Appel, E. A. 2021; 13 (578)


    Insulin was first isolated almost a century ago, yet commercial formulations of insulin and its analogs for hormone replacement therapy still fall short of appropriately mimicking endogenous glycemic control. Moreover, the controlled delivery of complementary hormones (such as amylin or glucagon) is complicated by instability of the pharmacologic agents and complexity of maintaining multiple infusions. In this review, we highlight the advantages and limitations of recent advances in drug formulation that improve protein stability and pharmacokinetics, prolong drug delivery, or enable alternative dosage forms for the management of diabetes. With controlled delivery, these formulations could improve closed-loop glycemic control.

    View details for DOI 10.1126/scitranslmed.abd6726

    View details for PubMedID 33504649

  • A Real-World Prospective Study of the Safety and Effectiveness of the Loop Open Source Automated Insulin Delivery System. Diabetes technology & therapeutics Lum, J., Bailey, R., Barnes-Lomen, V., Naranjo, D., Hood, K., Lal, R. A., Arbiter, B., Brown, A., DeSalvo, D. J., Pettus, J., Calhoun, P., Beck, R. W. 2020


    OBJECTIVE: To evaluate the safety and effectiveness of the Loop Do-It-Yourself (DIY) automated insulin delivery system.RESEARCH DESIGN AND METHODS: A prospective real-world observational study was conducted, which included 558 adults and children (age range 1 to 71 years, mean HbA1c 6.8±1.0%) who initiated Loop either on their own or with community-developed resources and provided data for 6 months.RESULTS: Mean time-in-range 70-180 mg/dL (TIR) increased from 67±16% at baseline (prior to starting Loop) to 73±13% during the 6 months (mean change from baseline 6.6%, 95% confidence interval 5.9% to 7.4%; P<0.001). TIR increased in both adults and children, across the full range of baseline HbA1c, and in participants with both high and moderate income levels. Median time <54 mg/dL was 0.40% at baseline and changed by -0.05% (95% confidence interval -0.09% to -0.03%, P<0.001). Mean HbA1c was 6.8±1.0% at baseline and decreased to 6.5±0.8% after 6 months (mean difference= -0.33%, 95% confidence interval -0.40% to -0.26%, P<0.001). The incidence rate of reported severe hypoglycemia events was 18.7 per 100 person-years, a reduction from the incidence rate of 181 per 100 person-years during the 3 months prior to the study. Among the 481 users providing Loop data at 6 months, median CGM use was 96% (interquartile range 91% to 98%) and median time Loop was modulating basal insulin was at least 83% (interquartile range 73% to 88%).CONCLUSIONS: The Loop open source system can be initiated with community-developed resources and used safely and effectively by adults and children with T1D.

    View details for DOI 10.1089/dia.2020.0535

    View details for PubMedID 33226840

  • A Randomized Trial of Closed-Loop Control in Children with Type 1 Diabetes. The New England journal of medicine Breton, M. D., Kanapka, L. G., Beck, R. W., Ekhlaspour, L., Forlenza, G. P., Cengiz, E., Schoelwer, M., Ruedy, K. J., Jost, E., Carria, L., Emory, E., Hsu, L. J., Oliveri, M., Kollman, C. C., Dokken, B. B., Weinzimer, S. A., DeBoer, M. D., Buckingham, B. A., Chernavvsky, D., Wadwa, R. P., iDCL Trial Research Group, Schoelwer, M., Breton, M., DeBoer, M., Gonder-Frederick, L., Chernavvsky, D., Robic, J., Emory, E., Voelmle, M., Conschafter, K., Morris, K., Barnett, C., Carr, K., Hellmann, J., Kime, M., Oliveri, M., Wadwa, R. P., Forlenza, G., Alonso, G. T., Slover, R., Messer, L., Cobry, E., Jost, E., Berget, C., Towers, L., Lange, S., Buckingham, B., Maahs, D., Lal, R., Ekhlaspour, L., Norlander, L., Hood, K., Town, M., Weir, C., Smith, K., Hsu, L., Shinksy, D., Viana, J., Cengiz, E., Weinzimer, S., Weyman, K., Carria, L., Zgorski, M., Ruedy, K., Beck, R., Borgman, S., Rusnak, J., Kanapka, L., Kollman, C., Murphy, C., Arreza-Rubin, G., Green, N., Kovatchev, B., Brown, S., Anderson, S., Laffel, L., Pinsker, J., Levy, C., Kudva, Y. C., Doyle, F. 3., Renard, E., Cobelli, C., Reznik, Y., Lum, J., Janicek, R., Gabrielson, D. 2020; 383 (9): 836–45


    BACKGROUND: A closed-loop system of insulin delivery (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes.METHODS: In a 16-week, multicenter, randomized, open-label, parallel-group trial, we assigned, in a 3:1 ratio, children 6 to 13 years of age who had type 1 diabetes to receive treatment with the use of either a closed-loop system of insulin delivery (closed-loop group) or a sensor-augmented insulin pump (control group). The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring.RESULTS: A total of 101 children underwent randomization (78 to the closed-loop group and 23 to the control group); the glycated hemoglobin levels at baseline ranged from 5.7 to 10.1%. The mean (±SD) percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter increased from 53±17% at baseline to 67±10% (the mean over 16 weeks of treatment) in the closed-loop group and from 51±16% to 55±13% in the control group (mean adjusted difference, 11 percentage points [equivalent to 2.6 hours per day]; 95% confidence interval, 7 to 14; P<0.001). In both groups, the median percentage of time that the glucose level was below 70 mg per deciliter was low (1.6% in the closed-loop group and 1.8% in the control group). In the closed-loop group, the median percentage of time that the system was in the closed-loop mode was 93% (interquartile range, 91 to 95). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either group.CONCLUSIONS: In this 16-week trial involving children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with the use of a closed-loop system than with the use of a sensor-augmented insulin pump. (Funded by Tandem Diabetes Care and the National Institute of Diabetes and Digestive and Kidney Diseases; number, NCT03844789.).

    View details for DOI 10.1056/NEJMoa2004736

    View details for PubMedID 32846062

  • An Intolerable Burden: Suicide, Intended Self-Injury and Diabetes. Canadian journal of diabetes Barnard-Kelly, K. D., Naranjo, D., Majidi, S., Akturk, H. K., Breton, M., Courtet, P., Olie, E., Lal, R. A., Johnson, N., Atkinson, M., Renard, E. 2020

    View details for DOI 10.1016/j.jcjd.2020.01.008

    View details for PubMedID 32305294

  • Insulin Pumps. Diabetes technology & therapeutics Lal, R. n., Leelarathna, L. n. 2020; 22 (S1): S17–S31

    View details for DOI 10.1089/dia.2020.2502

    View details for PubMedID 32069156

  • Primary Care Providers in California and Florida Report Low Confidence in Providing Type 1 Diabetes Care. Clinical diabetes : a publication of the American Diabetes Association Lal, R. A., Cuttriss, N. n., Haller, M. J., Yabut, K. n., Anez-Zabala, C. n., Hood, K. K., Sheehan, E. n., Basina, M. n., Bernier, A. n., Baer, L. G., Filipp, S. L., Wang, C. J., Town, M. A., Gurka, M. J., Maahs, D. M., Walker, A. F. 2020; 38 (2): 159–65


    People with type 1 diabetes may receive a significant portion of their care from primary care providers (PCPs). To understand the involvement of PCPs in delivering type 1 diabetes care, we performed surveys in California and Florida, two of the most populous and diverse states in the United States. PCPs fill insulin prescriptions but report low confidence in providing type 1 diabetes care and difficulty accessing specialty referrals to endocrinologists.

    View details for DOI 10.2337/cd19-0060

    View details for PubMedID 32327888

    View details for PubMedCentralID PMC7164993

  • THE GUIDED TRANSFER OF CARE IMPROVES ADULT CLINIC SHOW RATE. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists Lal, R. A., Maahs, D. M., Dosiou, C. n., Aye, T. n., Basina, M. n. 2020


    Objective Every year 500,000 youths in the U.S. with chronic disease turn 18 and eventually require transfer to adult subspecialty care. Evidence-based interventions on the organization of transfer of care are limited, although engagement and retention in adult clinic are considered appropriate outcomes. Sustained continuity of care improves patient satisfaction and reduces hospitalization. Methods We conducted a prospective non-randomized cohort study of patients with pediatric endocrine conditions, age 16-26 years, enrolled upon referral to the adult endocrine clinic of a physician trained in both adult and pediatric endocrinology (Med+Peds Endocrinologist). Patients differed based on whether their referral originated from another pediatric endocrinologist (traditional transfer) or if the Med+Peds Endocrinologist previously saw the patient in his pediatric endocrine clinic (guided transfer). Rather than relying on arbitrary age criteria, guided transfer to adult clinic occurred when physician and patient considered it appropriate. The primary outcome was show rate at the first and second adult visits. Results Of 36 patients, 21 were referred by another pediatric endocrinologist and 15 underwent guided transfer. For traditional transfer, show rate to the first and second visit was 38% compared to 100% in the guided transfer group (p = 0.0001). Subgroup analysis of 27 patients with diabetes revealed that both groups had similar initial HbA1c (p = 0.38) and the guided transfer group maintained HbA1c. Conclusions Most traditional transfers were unsuccessful. Guided transfer was significantly more effective, with every patient successfully transferring, and could be implemented with adult endocrinologists willing to see patients in the pediatric clinic.

    View details for DOI 10.4158/EP-2019-0470

    View details for PubMedID 32045296

  • Fast-Acting Insulin Aspart Use with the MiniMed™ 670G System. Diabetes technology & therapeutics Hsu, L. J., Buckingham, B. A., Basina, M. n., Ekhlaspour, L. n., von Eyben, R. n., Wang, J. n., Lal, R. A. 2020


    BACKGROUND This study assessed the efficacy and safety of ultra-rapid insulin Fiasp® in the hybrid closed-loop MiniMed™ 670G system. METHODS This was a pilot randomized, double-blinded, cross-over study among established MiniMed™ 670G users comparing percent time in range (TIR) and hypoglycemia for Novolog® and Fiasp®. Following two weeks optimization with their home insulin, participants were randomized to receive Novolog® or Fiasp® for two weeks, followed by the other insulin for the next two weeks. Data from the second week of blinded insulin use was analyzed to allow one week for 670G adaptation. During the second week, individuals were asked to eat the same breakfast for three days to assess differences in meal pharmacodynamics. RESULTS Nineteen adults were recruited with mean age of 40±18 years, diabetes duration of 27±12 years and median HbA1c of 7.1 (6.9,7.5)%, using 0.72 (0.4,1.2) units/kg/day. For Novolog® and Fiasp® respectively the %TIR (70-180mg/dL) was 75.3±9.5 and 78.4 ±9.3; %time <70mg/dL was 3.1±2.1 and 2.3±2.0; %time >180mg/dL was 21.6±9.0 and 19.3±8.9; mean glucose was 147±12 and 146±12mg/dL; coefficient of variation was 28.6±4.5% and 26.8±4.4%; %time in Auto Mode 86.4±9.2 and 84.4±9.2. All comparisons were non-significant for insulin type. Total daily dose (Novolog® 48.8±28.4 vs. Fiasp® 52.4±31.7 units; p=0.01) and daily basal (Novolog® 17.6 (15.5,33.8) vs. Fiasp® 19.1 (15.3,38.5) units; p=0.07) correlated with TIR and %time >180mg/dL. For insulin delivery in Auto Mode there was no statistical difference in total daily dose or daily basal between arms. Paired analysis for matched breakfast meals revealed no significant differences in time to maximum glucose, peak glucose or glucose excursion. CONCLUSIONS In this pilot study the use of either Novolog® or Fiasp® in a commercially available MiniMed™ 670G system operating in Auto Mode resulted in clinically similar glycemic outcomes, with a slight increase in daily insulin requirements using Fiasp®.

    View details for DOI 10.1089/dia.2020.0083

    View details for PubMedID 32520594

  • Suicide and Self-inflicted Injury in Diabetes: A Balancing Act. Journal of diabetes science and technology Barnard-Kelly, K. D., Naranjo, D., Majidi, S., Akturk, H. K., Breton, M., Courtet, P., Olie, E., Lal, R. A., Johnson, N., Renard, E. 2019: 1932296819891136


    Glycemic control in type 1 diabetes mellitus (T1DM) remains a challenge for many, despite the availability of modern diabetes technology. While technologies have proven glycemic benefits and may reduce excess mortality in some populations, both mortality and complication rates remain significantly higher in T1DM than the general population. Diabetes technology can reduce some burdens of diabetes self-management, however, it may also increase anxiety, stress, and diabetes-related distress. Additional workload associated with diabetes technologies and the dominant focus on metabolic control may be at the expense of quality-of-life. Diabetes is associated with significantly increased risk of suicidal ideation, self-harm, and suicide. The risk increases for those with diabetes and comorbid mood disorder. For example, the prevalence of depression is significantly higher in people with diabetes than the general population, and thus, people with diabetes are at even higher risk of suicide. The Center for Disease Control and Prevention reported a 24% rise in US national suicide rates between 1999 and 2014, the highest in 30 years. In the United Kingdom, 6000 suicides occur annually. Rates of preventable self-injury mortality stand at 29.1 per 100 000 population. Individuals with diabetes have an increased risk of suicide, being three to four times more likely to attempt suicide than the general population. Furthermore, adolescents aged 15 to 19 are most likely to present at emergency departments for self-inflicted injuries (9.6 per 1000 visits), with accidents, alcohol-related injuries, and self-harm being the strongest risk factors for suicide, the second leading cause of death among 10 to 24 year olds. While we have developed tools to improve glycemic control, we must be cognizant that the psychological burden of chronic disease is a significant problem for this vulnerable population. It is crucial to determine the psychosocial and behavioral predictors to uptake and continued use of technology in order to aid the identification of those individuals most likely to realize benefits of any intervention as well as those individuals who may require more support to succeed with technology.

    View details for DOI 10.1177/1932296819891136

    View details for PubMedID 31801353

  • Perspectives on long-acting growth hormone therapy in children and adults. Archives of endocrinology and metabolism Lal, R. A., Hoffman, A. R. 2019; 63 (6): 601–7


    Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7.

    View details for DOI 10.20945/2359-3997000000190

    View details for PubMedID 31939485

  • Fluoroscopic-assisted laparoscopic retrieval of retained glucose sensor wire from the omentum. Clinical case reports Sang, A. X., Lal, R., August, A., Danzer, E., Buckingham, B., Mueller, C. M. 2019; 7 (9): 1717-1720


    We describe a case in which retained wires from a continuous glucose monitor were removed from the abdominal wall and peritoneum of a 6-year-old boy. We highlight a concern for continuous glucose monitor use in children and discuss surgical techniques used to retrieve tiny, mobile objects from complex body cavities.

    View details for DOI 10.1002/ccr3.2348

    View details for PubMedID 31534734

    View details for PubMedCentralID PMC6745354

  • Fluoroscopic-assisted laparoscopic retrieval of retained glucose sensor wire from the omentum CLINICAL CASE REPORTS Sang, A. X., Lal, R., August, A., Danzer, E., Buckingham, B., Mueller, C. M. 2019

    View details for DOI 10.1002/ccr3.2348

    View details for Web of Science ID 000478842500001

  • Optimizing Basal Insulin Dosing. The Journal of pediatrics Lal, R. A., Maahs, D. M. 2019

    View details for DOI 10.1016/j.jpeds.2019.07.030

    View details for PubMedID 31383469

  • Realizing a Closed-Loop (Artificial Pancreas) System for the Treatment of Type 1 Diabetes. Endocrine reviews Lal, R. A., Ekhlaspour, L., Hood, K., Buckingham, B. 2019


    Recent, rapid changes in the treatment of type 1 diabetes have allowed for commercialization of an "artificial pancreas" which is better described as a closed-loop controller of insulin delivery. This review presents the current state of closed-loop control systems and expected future developments with a discussion of the human factor issues in allowing automation of glucose control. The goal of these systems is to minimize or prevent both short and long-term complications from diabetes and to decrease the daily burden of managing diabetes. The closed-loop systems are generally very effective and safe at night, have allowed for improved sleep and have decreased the burden of diabetes management overnight. However, there are still significant barriers to achieving excellent daytime glucose control while simultaneously decreasing the burden of daytime diabetes management. These systems utilize a subcutaneous continuous glucose sensor, an algorithm that accounts for the current glucose and rate of change of the glucose, and the amount of insulin which has already been delivered in order to safely deliver insulin to control hyperglycemia, while minimizing the risk of hypoglycemia. The future challenge will be to allow for full closed-loop control with minimal burden on the patient during the day alleviating meal announcements, carbohydrate counting, alerts and maintenance. The human factors involved with interfacing with a closed-loop system and allowing the system to take control of diabetes management are significant. It is important to find a balance between enthusiasm and realistic expectations and experiences with closed loop.

    View details for DOI 10.1210/er.2018-00174

    View details for PubMedID 31276160

  • Diabetes Technology and Therapy in the Pediatric Age Group. Diabetes technology & therapeutics Maahs, D. M., Lal, R., Shalitin, S. 2019; 21 (S1): S123–S137

    View details for DOI 10.1089/dia.2019.2510

    View details for PubMedID 30785328

  • One Year Clinical Experience of the First Commercial Hybrid Closed-Loop. Diabetes care Lal, R. A., Basina, M. n., Maahs, D. M., Hood, K. n., Buckingham, B. n., Wilson, D. M. 2019


    In September 2016, the U.S. Food and Drug Administration approved the Medtronic 670G "hybrid" closed-loop system. In Auto Mode, this system automatically controls basal insulin delivery based on continuous glucose monitoring data, but requires users enter carbohydrates and blood glucose for boluses. To track real-world experience with this first commercial closed-loop device, we prospectively followed pediatric and adult patients starting the 670G system.This was a 1-year prospective observational study of patients with type 1 diabetes starting the 670G system between May 2017 and May 2018 in clinic.A total of 84 patients received 670G and consented, 5 never returned for follow-up, with 79 (aged 9-61 years) providing data at 1 week and 3, 6, 9, and/or 12 months after Auto Mode initiation. For the 86% (68 out of 79) with 1-week data, 99% (67 out of 68) successfully started. By 3 months, at least 28% (22 out of 79) stopped using Auto Mode; at 6 months, 34% (27 out of 79); at 9 months, 35% (28 out of 79); and by 12 months, 33% (26 out of 79). The primary reason for continuing Auto Mode was desire for increased time in range. Reasons for discontinuation included sensor issues in 62% (16 out of 26), problems obtaining supplies in 12% (3 out of 26), hypoglycemia fear in 12% (3 out of 26), multiple daily injection preference in 8% (2 out of 26), and sports in 8% (2 out of 26). At all visits, there was a significant correlation between hemoglobin A1c (HbA1c) and Auto Mode utilization.While Auto Mode utilization correlates with improved glycemic control, a focus on usability and human factors is necessary to ensure use of Auto Mode. Alarms and sensor calibration are a major patient concern, which future technology should alleviate.

    View details for DOI 10.2337/dc19-0855

    View details for PubMedID 31548247

  • Long-Acting Growth Hormone Preparations in the Treatment of Children. Pediatric endocrinology reviews : PER Lal, R. A., Hoffman, A. R. 2018; 16 (Suppl 1): 162–67


    Human growth hormone (hGH), which had been in use since 1958, was supplanted by recombinant human growth hormone (rhGH) in 1985 for those with growth hormone deficiency (GHD). Adherence to daily subcutaneous growth hormone is challenging for patients. Thus, several companies have pursued the creation of long acting rhGH. These agents can be divided broadly into depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding GH and GH fusion proteins. Nutropin Depot is the only long acting rhGH ever approved by the U.S. Food and Drug Administration, and it was removed from the market in 2004. Of the approximately seventeen candidate drugs, only a handful remain under active clinical investigation or are commercially available.

    View details for PubMedID 30378794

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

    View details for PubMedID 29916743

  • Postmenopausal Hyperandrogenism. Journal of women's health care Lal, R. A., Basina, M. 2018; 7 (1)

    View details for DOI 10.4172/2167-0420.1000e132

    View details for PubMedID 32284912

  • A Case Report of Hypoglycemia and Hypogammaglobulinemia: DAVID syndrome in a patient with a novel NFKB2 mutation. journal of clinical endocrinology and metabolism Lal, R. A., Bachrach, L. K., Hoffman, A. R., Inlora, J., Rego, S., Snyder, M. P., Lewis, D. B. 2017


    DAVID syndrome (Deficient Anterior pituitary with Variable Immune Deficiency) is a rare disorder in which children present with symptomatic ACTH deficiency preceded by hypogammaglobulinemia from B-cell dysfunction with recurrent infections, termed common variable immunodeficiency (CVID). Subsequent whole exome sequencing studies have revealed germline heterozygous C-terminal mutations of NFKB2 as either a cause of DAVID syndrome or of CVID without clinical hypopituitarism. However, to the best of our knowledge there have been no cases in which the endocrinopathy has presented in the absence of a prior clinical history of CVID.A previously healthy 7 year-old boy with no history of clinical immunodeficiency, presented with profound hypoglycemia and seizures. He was found to have secondary adrenal insufficiency and was started on glucocorticoid replacement. An evaluation for autoimmune disease, including for anti-pituitary antibodies, was negative. Evaluation unexpectedly revealed hypogammaglobulinemia (decreased IgG, IgM, and IgA). He had moderately reduced serotype-specific IgG responses following pneumococcal polysaccharide vaccine. Subsequently, he was found to have growth hormone (GH) deficiency. Six years after initial presentation, whole exome sequencing revealed a novel de novo heterozygous NFKB2 missense mutation c.2596A>C (p.Ser866Arg) in the C-terminal region predicted to abrogate the processing of the p100 NFKB2 protein to its active p52 form.Isolated early-onset ACTH deficiency is rare and C-terminal region NFKB2 mutations should be considered as an etiology even in the absence of a clinical history of CVID. Early immunologic evaluation is indicated in the diagnosis and management of isolated ACTH deficiency.

    View details for DOI 10.1210/jc.2017-00341

    View details for PubMedID 28472507

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

    View details for DOI 10.1089/dia.2017.0013

    View details for PubMedID 28541138

  • An unusual cause of hyperglycemia JOURNAL OF POSTGRADUATE MEDICINE Lal, R., Loomba-Albrecht, L. A., Bremer, A. A. 2011; 57 (4): 343–46

    View details for DOI 10.4103/0022-3859.90092

    View details for Web of Science ID 000298626200018

    View details for PubMedID 22120869

  • Amyloid-beta and Glucose Metabolism in Alzheimer's Disease JOURNAL OF ALZHEIMERS DISEASE Furst, A. J., Lal, R. A. 2011; 26: 105-116


    This study used PET with the amyloid-β (Aβ) imaging agent 11 C Pittsburgh Compound-B (PIB) and the glucose metabolic tracer 18F-fluorodeoxyglucose (FDG) to map the relationship of Aβ deposition to regional glucose metabolism in Alzheimer's disease (AD). Comparison of 13 AD patients' FDG scans with 11 healthy controls confirmed a typical temporo-parietal hypometabolic pattern in AD. In contrast, PIB distribution-volume-ratios showed a distinct pattern of specific tracer retention in fronto-temporo-parietal regions and striatum in AD with peaks in left frontal cortex, precuneus, temporal cortex, striatum and right posterior cingulate. There were no region-to-region or within region correlations between FDG and PIB uptake in PIB positive AD patients but when the impact of Aβ load on glucose metabolism was assessed via probabilistic maps, increased amyloid burden was coupled with decreased metabolism in temporo-parietal regions and the posterior cingulate. However, importantly, severe Aβ burden was not associated with comparable metabolic decreases in large parts of the frontal lobes, the striatum and the thalamus.

    View details for DOI 10.3233/JAD-2011-0066

    View details for Web of Science ID 000297842800008

    View details for PubMedID 21971455

  • Amyloid-beta and Glucose Metabolism in Alzheimer's Disease HANDBOOK OF IMAGING THE ALZHEIMER BRAIN Furst, A. J., Lal, R. A., Ashford, J. W., Rosen, A., Adamson, M., Bayley, P., Sabri, O., Furst, A., Black, S. E., Weiner, M. 2011; 2: 235–46
  • Striatal Dopamine and Working Memory CEREBRAL CORTEX Landau, S. M., Lal, R., O'Neil, J. P., Baker, S., Jagust, W. J. 2009; 19 (2): 445-454


    Recent studies have emphasized the importance of dopamine projections to the prefrontal cortex (PFC) for working memory (WM) function, although this system has rarely been studied in humans in vivo. However, dopamine and PFC activity can be directly measured with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), respectively. In this study, we examined WM capacity, dopamine, and PFC function in healthy older participants in order to test the hypothesis that there is a relationship between these 3 factors. We used the PET tracer 6-[18F]fluoro-L-m-tyrosine to measure dopamine synthesis capacity in the striatum (caudate, putamen), and event-related fMRI to measure brain activation during different epochs (cue, delay, probe) of a WM task. Caudate (but not putamen) dopamine correlated positively with WM capacity, whereas putamen (but not caudate) dopamine correlated positively with motor speed. In addition, delay-related fMRI activation in a left inferior prefrontal region was related to both caudate dopamine and task accuracy, suggesting that this may be a critical site for the integration of WM maintenance processes. These results provide new evidence that striatal dopaminergic function is related to PFC-dependent functions, particularly brain activation and behavioral performance during WM tasks.

    View details for DOI 10.1093/cercor/bhn095

    View details for Web of Science ID 000262518800019

    View details for PubMedID 18550595

    View details for PubMedCentralID PMC2733326

  • A beta Amyloid and Glucose Metabolism in Three Variants of Primary Progressive Aphasia ANNALS OF NEUROLOGY Rabinovici, G. D., Jagust, W. J., Furst, A. J., Ogar, J. M., Racine, C. A., Mormino, E. C., O'Neil, J. P., Lal, R. A., Dronkers, N. F., Miller, B. L., Gorno-Tempini, M. L. 2008; 64 (4): 388-401


    Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, Abeta amyloidosis, and glucose metabolism in three PPA variants using [11C]-Pittsburgh compound B ([11C]PIB) and [18F]-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG-PET).Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing. [11C]PIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference). [18F]FDG images were normalized to pons. Partial volume correction was applied.Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) (p < 0.02). In PIB-positive PPA, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (n = 10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG uptake was significant asymmetric (favoring left hypometabolism) in PPA (p < 0.005) but not in AD.LPA is associated with Abeta amyloidosis, suggesting that subclassification of PPA based on language features can help predict the likelihood of AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD.

    View details for DOI 10.1002/ana.21451

    View details for Web of Science ID 000260845000007

    View details for PubMedID 18991338

    View details for PubMedCentralID PMC2648510