Beta Bionics Research Articles

781-P: Progressive Acceleration of Insulin Exposure over Seven Days of Infusion Set Wear

Insulin exposure and action are known to differ on each of 3 days of infusion set wear during CSII. We extend these observations to 1 week in a pilot phase study comparing conventional Teflon angled infusion sets to a prototype extended wear set using Capillary Biomedical SteadiFlow™ technology. Participants with T1DM for >12 months, A1C <8.5%, c-peptide <0.6 nmol/L, and ≥6 months use of Medtronic model 530G or higher were enrolled in a 2-period crossover euglycemic clamp study; clamps were performed after fasting overnight stabilization with IV insulin. Five men and 2 women, mean duration of diabetes 22.5 (16.6 SD) years and mean BMI 27.6 (3.8 SD) kg/m2 were enrolled; 4 completed all 8 clamps, 2 completed 7 clamps and 1 completed 1 clamp. We present the pharmacokinetic profiles of insulin lispro, 0.15 U/kg delivered by bolus infusion on Days 0, 3, 5 and 7 of infusion set wear. The Figure shows aggregate results from Control and Investigational infusion sets for insulin concentration (mean±SEM) vs. time by day of set wear. Statistically significant decreases from Day 0 to Day 7 were seen for tmax (p≤0.001) , t50% (early) (p<0.002) , t50% (late) (p<0.001) , and Mean Residence Time (p<0.001) . AUC0-300 declined by approximately 20% from Day 0 to Day 7 (p<0.11) . These results confirm and extend previous observations showing significant progressive acceleration of insulin exposure as a function of duration of infusion set wear time. Disclosure T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker's Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. J.R.Kastner: Consultant; Capillary Biomedical, Inc. P.Strange: Other Relationship; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. L.Shi: None. K.A.Oberg: Consultant; Beta Bionics, Inc., Companion Medical, Tandem Diabetes Care, Inc. J.I.Joseph: Advisory Panel; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. P.J.Strasma: Board Member; Capillary Biomedical, Inc., Employee; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. D.B.Muchmore: Consultant; Capillary Biomedical, Inc., Diasome, Zucara Therapeutics, Stock/Shareholder; Capillary Biomedical, Inc., Diasome. Funding National Institutes of Health (2R44DK110969-02)

33-OR: ADA Presidents' Select Abstract: Glycemic Outcomes over 12 Months in Very Young Children with the Omnipod 5 Automated Insulin Delivery (AID) System

The Omnipod 5 AID System is a tubeless hybrid closed-loop system with on-body operation and customizable glucose targets. Safe and effective system use was demonstrated in children aged 2-5.9y with type 1 diabetes (T1D) during a 3-mo pivotal study. To evaluate durability of glycemic benefit, we analyzed results from 9mo of an ongoing extension study, totaling 12mo of system use. In the pivotal study, participants used the system for 3mo at home, after 14d of their standard therapy (ST, pump or multiple daily injections) . They were then invited to participate in the extension study. Safety endpoints were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) . Glycemic outcomes were A1C and percent time in ranges (TIR 70-180 mg/dL, TBR <70 mg/dL, TAR >180 mg/dL) during 3-mo AID intervals compared with ST. All pivotal trial participants (N=80) , aged (mean±SD) 4.7±1.0y with T1D duration 2.3±1.1y and total daily insulin of 14±4U (range: 5.3-27U) at baseline, enrolled in the extension. Improved outcomes were observed for up to 12mo, including lower A1C and greater TIR during each AID interval compared with ST (all p<0.05, Table) . There were no episodes of DKA or SH in the 12-mo study. The safety and improved glycemic outcomes from the initial 3mo pivotal study persisted for an additional 9mo, indicating the potential long-term benefit of the Omnipod 5 System in very young children with T1D. Disclosure D.Desalvo: Consultant; Dexcom, Inc., Insulet Corporation, Research Support; Insulet Corporation. D.W.Hansen: None. T.T.Ly: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation. Omnipod 5 in preschoolers study group: n/a. B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker's Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. G.P.Forlenza: Advisory Panel; Lilly, Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. B.A.Buckingham: Advisory Panel; Arecor, Lilly Diabetes, Medtronic, Other Relationship; Insulet Corporation, Research Support; Insulet Corporation, Lilly Diabetes, Medtronic. A.B.Criego: Advisory Panel; Insulet Corporation, Other Relationship; Medscape, Sanofi, Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic. M.Schoelwer: Other Relationship; Dexcom, Inc., Research Support; Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. S.A.Macleish: Advisory Panel; Insulet Corporation. J.Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Speaker's Bureau; Lilly Diabetes. Funding Insulet Corporation

676-P: Difference in CGM Estimated Hemoglobin A1c in Adults with Type 1 and Type 2 Diabetes

The relationship between mean glucose measured using a continuous glucose monitor (CGM) and hemoglobin A1c (A1C) was evaluated in adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) . Data from participants enrolled in the MOBILE, DIAMOND, and WISDM trials and randomized to the CGM arm were used in the analysis. Follow-up visits collected A1C measured by a central laboratory at 8 months post-randomization in the MOBILE study and 6 months post-randomization in DIAMOND and WISDM studies. CGM data collected in the 91 days prior to the follow-up visit, when glucose control was thought to be relatively stable, was used to compute mean glucose. A least squares linear regression model estimated A1C using mean glucose as a predictor, and models were fit separately by diabetes type. 199 participants with T1D and 175 participants with T2D were included in the analysis. Mean age was 57±15 years among those with T1D and 58±years among those with T2D. Estimated A1C was similar but slightly higher for participants with T2D vs. T1D for the same mean glucose (Table) . Analyses restricting to White non-Hispanic cohort yielded similar results. Spearman partial correlation coefficients for mean glucose vs. A1C were 0.76 for T1D and 0.84 for T2D. Estimates of A1C based on CGM measured mean glucose were slightly higher for those with T2D compared with T1D. Disclosure M.Salam: Advisory Panel; Lilly Diabetes, Consultant; Neurocrine Biosciences, Inc., Research Support; Mylan N.V., Neurocrine Biosciences, Inc. R.Bailey: None. P.Calhoun: None. J.B.Mcgill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; Dexcom, Inc., Novo Nordisk. R.Beck: Consultant; Diasome, Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Research Support; Ascensia Diabetes Care, Beta Bionics, Inc., Bigfoot Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Tandem Diabetes Care, Inc. D.A.Price: Employee; Dexcom, Inc.

405-P: Glycemic Control Impacts Renal Function Decline among People with Type 1 Diabetes after the Onset of Diabetic Kidney Disease

While poor glycemic control increases the risk of diabetic kidney disease (DKD) , its impact on renal function decline among those with established DKD is unclear. To examine this, we tested the relationship between baseline HbA1c and renal outcomes in the 3-year Preventing Early Renal Loss (PERL) trial (n=530) , which included persons with type 1 diabetes (T1D) and early-to-moderate DKD (eGFR 40-100 ml/min/1.73m2 and persistent albuminuria and/or ongoing GFR decline) . In Cox regression models, baseline HbA1c was associated (p<0.0001) with a higher risk of progression to ESKD or serum creatinine doubling (HR 1.87 per HbA1c unit increment, 95% CI 1.42-2.47) , and in mixed-effects linear regression models, with 0.87 and 0.51 ml/min/1.73m2/year higher rates of estimated glomerular filtration rate (eGFR) and iohexol GFR decline (p<0.00for both) . Baseline albumin excretion rate (AER) was a modifier of the HbA1c-GFR slope relationships (p for interaction <0.05) , such that HbA1c was associated with a higher rate of GFR decline among those with AER≥200 μg/min than among those with AER<20 or 20≤AER<200 (Fig.1) . Thus, worse glycemic control in PERL was a major determinant of GFR decline and ESKD risk after DKD onset, especially in persons with overt proteinuria. Efforts to normalize HbA1c should continue among such persons. Disclosure H.Shah: None. J.B.Mcgill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; Dexcom, Inc., Novo Nordisk. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. C.Wu: None. A.Galecki: None. M.Mauer: None. A.Doria: Research Support; Novo Nordisk Foundation. Perl consortium: n/a. Funding National Institutes of Health UC4DK101108Juvenile Diabetes Research Foundation 17-2012-377The Leona M. and Harry B. Helmsley Charitable Trust 2018PG-T1D014

596-P: Diabetes Responsibility Moderates Relationship between Fear of Hypoglycemia and A1C in Adolescents with Type 1 Diabetes

Fear of hypoglycemia (FOH) is not consistently correlated with A1C in youth with T1D, but few studies have taken other psychosocial variables into account. This study examined T1D responsibility as a moderator of the relationship between FOH and A1C. N=1youth ages 10-18 yrs (45.5% male; age=14.7±1.9 yrs; A1C=9.9±1.6%; T1D duration=6.5+3.4 yrs) completed the Maintain High Blood Glucose subscale of the Children’s Hypoglycemia Fear Survey (assesses behavioral manifestations of FOH) and Diabetes Family Responsibility Questionnaire (assesses distribution of T1D responsibility between child and caregiver) . Higher scores indicate greater FOH and caregiver responsibility, respectively. The main effect of T1D responsibility on A1C was not significant (p>0.05) , whereas the main effect of Maintain High Blood Glucose was (p=0.03) . Responsibility moderated the relationship between Maintain High Blood Glucose and A1C; child’s FOH had less of an effect on A1C if the caregiver had higher responsibility (B=-0.41, p=0.04; R2 =0.038, p<0.04) . Children who maintain their blood glucoses higher than recommended due to high FOH should have more parent involvement in their T1D care to minimize the deleterious impact of their fears on A1C. Future research should examine the Maintain High Blood Glucose subscale and other psychosocial moderators specifically in relation to glycemic outcomes. Disclosure E.R.Shaffer: None. H.K.O'donnell: None. G.T.Alonso: None. S.Majidi: None. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. R.Wadwa: Advisory Panel; Dompé, Consultant; Beta Bionics, Inc., Other Relationship; Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. K.A.Driscoll: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK113363)

1017-P: Relationship between Parent Fear of Hypoglycemia and Diabetes Family Conflict in Adolescents with Type 1 Diabetes

Few studies have examined the relationship between diabetes-related family conflict and parent fear of hypoglycemia (FOH) in adolescents, thus the current research evaluated this connection. This study specifically examined three subdimensions of FOH which parents of children with diabetes may experience: maintaining blood glucoses higher than medical recommendations, worrying about and/or feeling helplessness about preventing low blood glucoses, and worrying about social consequences associated with low blood glucoses. At the baseline visit of an RCT aimed at improving health outcomes of youth with elevated A1C (9-12% in the last year) , caregivers completed the Diabetes Family Conflict Scale and the Parent Hypoglycemia Fear Survey. N=1child-caregivers dyads (child age=14.7±1.9 years, T1D duration=6.5±3.4 years, A1C=9.9±1.6%; 53% female; 77% continuous glucose monitor; 82% insulin pump) . In three separate regression models, no child demographic or T1D clinical characteristics other than A1C were associated with family conflict. After controlling for A1C, only Worry/Helplessness About Low Blood Glucose (b=0.182; p=0.025) and Worry About Negative Social Consequences (b=0.532; p=0.008) significantly predicted parent-reported family conflict; Maintain High Blood Glucose (b=0.082; p=0.73) was not significant. This is the first study to demonstrate that caregivers’ worry about their adolescents having low blood glucoses is associated with diabetes-specific family conflict- a common adherence barrier for adolescents with T1D and their families. This finding supports screening caregivers for fear of hypoglycemia and incorporating into treatment when providing intervention for families with high levels of conflict. Important next steps include dyadic data analysis to understand how fear of hypoglycemia symptoms among child-caregiver dyads affect family conflict. Disclosure H.Manis: Other Relationship; Abbott Diabetes. H.K.O'donnell: None. G.T.Alonso: None. S.Majidi: None. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. R.Wadwa: Advisory Panel; Dompé, Consultant; Beta Bionics, Inc., Other Relationship; Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. K.A.Driscoll: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK113363)

279-OR: Self-Efficacy, Diabetes Distress, Self-Care, and Blood Glucose: Within-Person Pathways in Adults with T1D

Introduction: Research links self-efficacy and diabetes distress to suboptimal diabetes self-care and blood glucose (BG) regulation. However, most studies rely on between-person comparisons that cannot rule out confounding by unmeasured variables or capture the dynamic interplay among these variables in real time. Pairing continuous glucose monitoring (CGM) with ecological momentary assessment, we sought to illuminate pathways of influence among these variables in a diverse sample of adults with T1D. Methods: Participants (N=127, 41±15 yrs, 53% women, 39% Latino, 35% White, 10% Black) wore blinded CGM for 10-14 days and completed smartphone surveys 5-6 times per day. Using dynamic structural equation modeling, we evaluated within-person pathways shown in Figure 1. Results: Hypothesized pathways were significant, as were indirect effects of:1) morning self-efficacy on that day’s mean BG via diabetes distress and self-care and2) diabetes distress on mean BG via self-care. Similar results were observed for time in range and SD of BG. Conclusion: Our findings provide novel evidence for a sequential pathway of influence of psychological, emotional, and behavioral variables on BG regulation, observed over time and within individuals. These results provide a roadmap for interventions that target self-efficacy, diabetes distress, and self-care to improve BG regulation among adults with T1D. Disclosure J.S.Gonzalez: Consultant; Virta Health Corp. H.Jin: None. L.T.Pham: None. A.Ali: None. P.Lee: None. V.F.Ruelas: n/a. R.Basile: None. E.Pyatak: Research Support; Abbott Diabetes. D.Spruijt-metz: None. S.Schneider: None. A.L.Peters: Advisory Panel; Abbott Diabetes, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Shouti, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Other Relationship; Omada Health, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Stock/Shareholder; Teladoc Health. J.P.Crandall: Research Support; Abbott Diabetes. G.Crespo-ramos: None. H.Mendez-rodriguez: None. C.J.Hoogendoorn: None. S.Agarwal: Advisory Panel; Medtronic, Consultant; Beta Bionics, Inc. Funding National Institutes of Health (1R01DK121298-01; P30 DK111022)

774-P: Impact of Transition to Tandem Control-IQ on Sleep Awakenings in Youth with Type 1 Diabetes (T1D) and Their Parents

Youth with T1D and their parents are susceptible to diabetes-related nocturnal awakenings, which have been associated with reduced sleep duration and quality. We conducted an observational study of youth with T1D starting on the Tandem Control-IQ (CIQ) hybrid closed-loop (HCL) system to evaluate the impact of system use on sleep. Thirty-nine youth (age 11.1±3.6 yrs, T1D duration 2.5±3.0 yrs, 54% male) and a parent (age 42.5±6.7 yrs, 18% male) completed sleep diaries capturing the number of and reasons for nocturnal awakenings over a 7-day period. Analyses compared diaries from before starting CIQ (baseline) to 3- and 6-months after starting CIQ using a zero-inflated Poisson mixed model with random intercept for participants. Youth and parents reported significantly fewer total awakenings per night at 3- and 6-months compared to baseline (Table) . A significant decrease in diabetes-related awakenings was observed after 6 months in youth but not in parents. Following CIQ initiation, fewer nocturnal awakenings were reported by parents and youth, with youth additionally reporting significantly fewer diabetes-related awakenings at 6 months. Due to the subjective nature of diaries, the number of true awakenings may be different. The results suggest that HCL technology may be beneficial in reducing sleep disruptions in youth and parents. Disclosure A.J.Karami: None. L.Pyle: None. T.B.Vigers: None. E.Jost: Other Relationship; Tandem Diabetes Care, Inc. R.Wadwa: Advisory Panel; Dompé, Consultant; Beta Bionics, Inc., Other Relationship; Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. E.C.Cobry: None.

691-P: Closed-Loop Glycemic Control with the Insulin-Only Bionic Pancreas for the Management of Type 2 Diabetes

Closed-loop insulin delivery has been shown to improve glycemia in patients with type 1 diabetes (T1D) but fewer studies have applied these technologies to the management of type 2 diabetes (T2D). We conducted a random-order crossover feasibility study in 5 adults with T2D who used basal and prandial insulin, comparing automated glycemic control with the insulin-only bionic pancreas (BP) to usual care (UC) in the home-use setting. Each study period was one week long. Non-insulin diabetes medications besides metformin were held during the BP arm only. The BP utilized the same control algorithms previously tested in T1D. The system was initialized with participants’ body mass only; no information on insulin requirement or regimen was provided to the BP. Participants were encouraged to enter qualitative meal announcements (“typical”, “small”, or “ large” amounts of carbohydrate) for main meals but not for snacks. The BP used a target glucose of 100 mg/dl (110 mg/dl is the minimum target previously used by the insulin-only configuration in T1D studies). There was a nominal improvement in mean continuous glucose monitor (CGM) glucose in the BP compared to UC arms (137±8 vs. 153±21 mg/dl) with similar % time Disclosure J. Sherwood: None. C. A. Balliro: Consultant; Self; Beta Bionics, Inc., Novo Nordisk. M. Hillard: None. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. F. El-khatib: Employee; Self; Beta Bionics, Inc., Stock/Shareholder; Self; Beta Bionics, Inc. E. Damiano: Other Relationship; Self; Beta Bionics, Inc., Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S. J. Russell: Advisory Panel; Self; Companion Medical, ConvaTec Inc., Consultant; Self; Beta Bionics, Inc., Novo Nordisk, Other Relationship; Self; Beta Bionics, Inc., Research Support; Self; Beta Bionics, Inc., Novo Nordisk, Zealand Pharma A/S. Funding The Leona M. and Harry B. Helmsley Charitable Trust

216-OR: A Random-Order, Double-Blinded, Placebo-Controlled Study of the Bionic Pancreas in the Bihormonal vs. Insulin-Only Configurations Using Two Different Glucose Targets in Adults with Type 1 Diabetes in the Home-Use Setting

Objective: We evaluated the glycemic outcomes with 2 glucose targets in both configurations (bihormonal and insulin-only) of the bionic pancreas (BP) in a home-use study of adults with type 1 diabetes. Research Design and Methods: 20 participants completed a double-blinded, placebo-controlled (glucagon vs. placebo), random-order, four-arm cross-over trial comparing the bihormonal (BH) and insulin-only (IO) configurations of the BP, each using 2 glucose targets (110 and 130 mg/dl); each arm lasted 3 days. Co-primary outcomes were continuous glucose monitor (CGM) mean glucose level and time <54 mg/dl. Results: For the BH vs. IO configurations using the 130 mg/dl glucose target, the mean CGM glucose was 156±12 vs. 161±17 mg/dl (p=0.11) and the median percentage of time with CGM glucose <54 mg/dl was 0.0% [IQR 0-0.52%] vs. 0.0% [0-0.35%] (p=0.45). For the BH vs. IO configurations using the 110 mg/dl glucose target, the mean CGM glucose was 148±17 vs. 153±15 mg/dl (p=0.21) and the median percentage of time with CGM glucose <54 mg/dl was 0.0% [0-0%] vs. 0.52% [0.0-1.0%] (p=0.002). The nominal differences in mean CGM glucose between the 110 mg/dl and the 130 mg/dl glucose targets (8 mg/dl in each case) were not statistically significant in either the IO or BH configuration (p>0.05). There was less hypoglycemia in the IO configuration, but not the BH configuration, when using the 130 mg/dl target vs. the 110 mg/dl target (p=0.03). Conclusions: Both configurations of the BP provided safe and effective glycemic control using both glucose targets during home use. Hypoglycemia was lower with the BH configuration vs. the IO configuration using the 110 mg/dl target. Hypoglycemia was lower in the IO configuration when using the 130 mg/dl target vs. the 110 mg/dl target. Larger and longer studies will be needed to quantify differences in outcomes between the IO and BH configurations of the BP. Disclosure L. E. Castellanos: None. C. A. Balliro: Consultant; Self; Beta Bionics, Inc., Novo Nordisk. J. Sherwood: None. M. Tuffaha: None. M. Hillard: None. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. F. El-khatib: Employee; Self; Beta Bionics, Inc., Stock/Shareholder; Self; Beta Bionics, Inc. E. Damiano: Other Relationship; Self; Beta Bionics, Inc., Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S. J. Russell: Advisory Panel; Self; Companion Medical, ConvaTec Inc., Consultant; Self; Beta Bionics, Inc., Novo Nordisk, Other Relationship; Self; Beta Bionics, Inc., Research Support; Self; Beta Bionics, Inc., Novo Nordisk, Zealand Pharma A/S.

214-OR: Cambridge Hybrid Closed-Loop in Children and Adolescents with T1D: A Multicentre Six-Month Randomised Trial

Aims: We assessed safety and efficacy of Cambridge hybrid closed-loop (HCL) compared with usual care over 6 months in children and young people with T1D. Methods: In an open-label multicentre multinational parallel randomised controlled trial, we randomly assigned participants on insulin pump therapy aged 6 to 18 years to receive either HCL therapy (CL) or continue usual care (control) for 6 months. We used the same Cambridge model predictive control algorithm in two consecutive hardware iterations, FlorenceM then CamAPS FX. Primary endpoint was central laboratory HbA1c at 6 months. Results: We randomised 133 participants: 65 to CL and 68 to control (baseline HbA1c 8.2±0.7% vs. 8.3±0.8%). At 6 months mean HbA1c was 0.32% lower in CL compared to control (95% CI -0.59 to -0.04; p=0.02). Closed-loop usage was low (40% [26, 53]; median [IQR]) with FlorenceM due to hardware issues, and high (93% [88, 96]) with CamAPS FX. In the CamAPS FX CL group (n=21) HbA1c was 1.05% lower (95% CI -1.43 to -0.67; p Conclusion: Cambridge HCL is safe and significantly improves glycaemic control in children and young people with T1D. Efficacy relies on consistent usage of closed-loop, as demonstrated by CamAPS FX. Disclosure J. Fuchs: None. B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. N. Davis: None. L. Dimeglio: Advisory Panel; Self; MannKind Corporation. N. Mauras: Advisory Panel; Self; Novo Nordisk, Research Support; Self; LifeScan, Medtronic, Novo Nordisk. R. Besser: None. A. Ghatak: None. S. A. Weinzimer: Advisory Panel; Self; Dompe, Zealand Pharma A/S, Speaker’s Bureau; Self; Medtronic. K. K. Hood: Consultant; Self; Cecelia Health, Cercacor, LifeScan Diabetes Institute. D. Fox: None. L. Kanapka: None. C. K. Boughton: None. C. Kollman: Consultant; Self; Diasome Pharmaceuticals, Inc., Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. J. Sibayan: None. R. Beck: Consultant; Self; Bigfoot Biomedical, Inc., Diasome Pharmaceuticals, Inc., Insulet Corporation, Lilly Diabetes, vTv Therapeutics, Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Medtronic, Novo Nordisk, Tandem Diabetes Care. R. Hovorka: Research Support; Self; Abbott Laboratories, Dexcom, Inc., Medtronic, Speaker’s Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Stock/Shareholder; Self; CamDiab Ltd. Dan05 consortium: n/a. J. M. Allen: None. M. E. Wilinska: Consultant; Self; CamDiab Ltd. M. Tauschmann: None. L. Denvir: None. A. Thankamony: None. F. Campbell: n/a. R. Wadwa: Consultant; Self; Tandem Diabetes Care, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UC4DK108520)

70-OR: Evaluation of the Omnipod 5 Automated Insulin Delivery System in Very Young Children with Type 1 Diabetes (T1D)

The Omnipod 5 System is a novel hybrid closed-loop (HCL) system with full on-body operation. A tubeless insulin pump containing a personalized MPC algorithm communicates directly with a Dexcom G6 CGM to automate insulin delivery. Following demonstration of positive safety and efficacy in older children (≥6y) and adults, we evaluated the system in very young children (2-5.9y) with T1D. Preschoolers with T1D often have erratic eating behaviors and may dislike being tethered to devices, and parental concern may lead to permissive hyperglycemia. This HCL system may be ideal for young children, given its customizable glucose targets from 110-150mg/dL, wireless system interaction through a mobile application, and bolus calculator that incorporates CGM trend information. Also, the system has no minimum weight or total daily dose (TDD) requirement. Participants with T1D and A1C<10% used their respective standard therapies (ST) for 14d, and then transitioned to use of the HCL system for 3mo. Primary safety outcomes are the incidence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA). Primary effectiveness outcomes are change in A1C and percent of time in target range (TIR, 70-180 mg/dL) with the HCL system compared with ST. Baseline characteristics of participants (N=80) were (mean±SD) age 4±1y (range 2-5y), T1D duration 2.2±1.1y, and A1C 7.4±0.9%, with mean (range) TDD 13.7 (5.3-27.1) U/day and weight 20 (12-53) kg. There have been no serious adverse events, including SH and DKA, reported in over 5,254 person-days of HCL use. During the ST phase, TIR was 57.2±15.1%, time <54mg/dL was 0.8±1.7%, <70mg/dL was 3.4±3.9%, >180mg/dL was 39.4±16.5%, and ≥250mg/dL was 14.7±12.0%. The same efficacy analysis is planned for the 3-month HCL phase upon its completion in January 2021. This multi-center pivotal study has, to date, demonstrated safety of the Omnipod 5 System in very young children with T1D. At completion, this will be the largest study of HCL in this age group reported to date. Disclosure J. Sherr: Advisory Panel; Self; Cecelia Health, Insulet Corporation, Medtronic, Consultant; Self; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Speaker’s Bureau; Self; Lilly Diabetes. D. W. Hansen: None. T. T. Ly: Employee; Self; Insulet Corporation. Omnipod 5 in preschoolers study group: n/a. B. W. Bode: Advisory Panel; Self; Eli Lilly and Company, Consultant; Self; Bigfoot Biomedical, Inc., Companion Medical, Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Abvance Therapeutics, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Dompe, Eli Lilly and Company, Eyenuk, Inc., Insulet Corporation, Jaeb Center for Health Research, Medtronic, Nova Biomedical, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanofi, Senseonics, Viacyte, Inc., vTv Therapeutics, Xeris Pharmaceuticals, Inc., Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; Self; AgaMatrix, Aseko, Inc., Glytec, LLC. G. P. Forlenza: Advisory Panel; Self; Medtronic, Consultant; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. S. A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. A. B. Criego: Consultant; Self; Bigfoot Biomedical, Inc., Other Relationship; Self; Sanofi, Research Support; Self; Abbott Diabetes, Eli Lilly and Company, Insulet Corporation, Medtronic. D. Desalvo: Consultant; Self; Insulet Corporation, Research Support; Self; Insulet Corporation, Speaker’s Bureau; Self; Dexcom, Inc. S. A. Macleish: Advisory Panel; Self; Insulet Corporation. Funding Insulet Corporation

96-LB: Glycemic Management over 6 Months with the Omnipod 5 Automated Insulin Delivery System

Safe and effective use of the Omnipod 5 System was demonstrated in adults and children with type 1 diabetes (T1D) during a 3-month pivotal study. Longer studies are needed to evaluate durability of glycemic benefit. Those completing the pivotal study were invited to continue system use for an additional 12 months, with 95% enrolling in the extension. We present results from the first 3-month follow-up. Participants aged 6-70y with T1D≥6 months and A1C<10% used the system in Automated Mode at home. Following the pivotal study, A1C was measured again after 3 months (6 months of total use). Safety and efficacy endpoints were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) and change in A1C, respectively. Participants (n=217) were aged (mean±SD) 24±17y with T1D duration 11±11y. A1C was lower after 6 months of system use than at baseline for children and adults (p<0.001, Table). For children, A1C was not significantly different between end of pivotal and the 3-month extension, while adults had an additional -0.1% decrease (p<0.01). There was 1 episode of DKA and no episodes of SH during the 3-month extension phase. The safety and improved glycemic outcomes from the pivotal study persisted for an additional 3 months of system use in this large cohort of participants, with 99% continuing into the next extension phase. Sustained reduction of A1C indicates the potential long-term benefit of the Omnipod 5 System.View largeDownload slideView largeDownload slide DisclosureA. L. Carlson: Board Member; Self; JDRF, Other Relationship; Self; Medtronic, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Omnipod, Sanofi, UnitedHealth Group. J. Sherr: Advisory Panel; Self; Cecelia Health, Insulet Corporation, Medtronic, Consultant; Self; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Speaker’s Bureau; Self; Lilly Diabetes. S. N. Mehta: None. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. V. Shah: Advisory Panel; Self; Medscape, Sanofi, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi, vTv Therapeutics. A. Bhargava: Research Support; Self; Abbott, AbbVie Inc., Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Boston Therapeutics, Inc., Covance Inc., Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Insulet Corporation, Janssen Research & Development, LLC, Kowa Pharmaceuticals America, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Mylan N. V., Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics. R. S. Weinstock: Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. S. A. Macleish: Advisory Panel; Self; Insulet Corporation. D. Desalvo: Consultant; Self; Insulet Corporation, Research Support; Self; Insulet Corporation, Speaker’s Bureau; Self; Dexcom, Inc. T. C. Jones: None. G. Aleppo: Consultant; Self; Dexcom, Inc., Insulet Corporation, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. A. B. Criego: Consultant; Self; Bigfoot Biomedical, Inc., Other Relationship; Self; Sanofi, Research Support; Self; Abbott Diabetes, Eli Lilly and Company, Insulet Corporation, Medtronic. B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. T. T. Ly: Employee; Self; Insulet Corporation. Omnipod 5 research group: n/a. G. P. Forlenza: Advisory Panel; Self; Medtronic, Consultant; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. B. W. Bode: Advisory Panel; Self; Eli Lilly and Company, Consultant; Self; Bigfoot Biomedical, Inc., Companion Medical, Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Abvance Therapeutics, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Dompe, Eli Lilly and Company, Eyenuk, Inc., Insulet Corporation, Jaeb Center for Health Research, MedtroFundingInsulet Corporation

101-LB: Reported Satisfaction during the Medtronic Extended-Wear Infusion Set (EWIS) Pivotal Trial

Objective: Most insulin infusion sets (ISs) are labeled for 2- or 3-days use. The Medtronic EWIS is designed to increase wear time up to 7 days, and demonstrated a 74.8% survival rate (77.8%, excluding inadvertent early removal) in the pivotal trial (ClinicalTrials.gov: NCT04113694). This study reports on study participant satisfaction during the EWIS pivotal trial.Method: This multi-center (15), single-arm, non-randomized, non-inferiority trial in 259 participants (18-80yrs) with T1D using the MiniMed™ 670G system (with Humalog™ or Novolog™ insulin) involved wearing a 2- or 3-day IS for 2 weeks (run-in) followed by 12 consecutive EWIS wears (study phase). The latter was worn for ≥174 hours or until set failure. Participants completed a Medtronic Likert-based questionnaire at baseline and study exit. The averaged paired change in score at study-baseline was determined (Wilcoxon signed-rank test).Result: Reported satisfaction data during 2- or 3-day IS versus EWIS wear (Figure) show that ease and convenience of use, comfort, wear duration and time required to change a set were significantly improved with EWIS (p<0.001).Conclusion: These findings point to significantly greater satisfaction with the EWIS when compared with a 2- or 3-day IS, which may result in reduced care burden and improved adherence.View largeDownload slideView largeDownload slide DisclosureR. L. Brazg: Research Support; Self; Abbott Diabetes, Ascensia Diabetes Care, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., Roche Diagnostic USA, Senseonics. B. Horowitz: Research Support; Self; Abbott Laboratories, BD, Celgene, Crinetics Pharmaceuticals, Gan & Lee Pharmaceuticals, Medtronic, Speaker’s Bureau; Self; AstraZeneca, Lilly Diabetes, Merck & Co., Inc., Novo Nordisk Inc. K. B. Kaiserman: Advisory Panel; Self; Medtronic, Consultant; Self; Medtronic, Employee; Self; MannKind Corporation, Research Support; Self; Medtronic, Speaker’s Bureau; Self; Medtronic, Stock/Shareholder; Self; MannKind Corporation. S. Huang: None. V. Chen: Employee; Self; Medtronic. G. Zhang: Employee; Self; Medtronic. S. Chattaraj: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic. R. Vigersky: Employee; Self; Medtronic. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. Y. C. Kudva: Research Support; Self; Dexcom, Inc. S. K. Garg: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Medtronic. G. Grunberger: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk. A. Cavale: Research Support; Self; Eli Lilly and Company, Medtronic. J. Thrasher: Advisory Panel; Self; Medtronic, Board Member; Self; Medtronic, Consultant; Self; Medtronic, Research Support; Self; Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Mylan N. V., Novo Nordisk, Sanofi, Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Medtronic, Sanofi. A. Bhargava: Research Support; Self; Abbott, AbbVie Inc., Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Boston Therapeutics, Inc., Covance Inc., Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Insulet Corporation, Janssen Research & Development, LLC, Kowa Pharmaceuticals America, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Mylan N. V., Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics. B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care.

1240-P: Changes in Protein Expression during Islet Regeneration in a Cystic Fibrosis-Related Diabetes (CFRD) Ferret Model

Diabetes is a common complication among persons with cystic fibrosis (CF), affecting nearly 20% of adolescents and 50% of all adults with CF. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) knockout (KO) ferret is a well-characterized animal model of CF that exhibits distinct periods of dysglycemia and pancreatic remodeling that are similar to patterns observed in humans. After the first month of life (normoglycemia/Phase I), hyperglycemia develops during the second month of life (Phase II) with reduced islet mass, followed by a period of near normoglycemia (Phase III) during which the islet mass regenerates, followed by persistent hyperglycemia/CFRD at the 4th month of life (Phase IV). While dynamic changes in islet hormone mRNA levels have been described across these phases, changes in protein expression patterns have not been characterized. To this end, immunofluorescence was performed to characterize islet hormone expression patterns in age-matched CFTR KO and wild type (WT) ferrets, focusing on the regenerative Phase III. The relative intensity of immunofluorescent staining per islet area was calculated. Compared to WT ferrets, the relative staining intensity of insulin and glucagon increased (4.687 vs. 3.228, p&amp;lt;0.05 and 0.827 vs. 0.238, p&amp;lt;0.0001, respectively ), while the intensity of proinsulin decreased (1.061 vs. 1.455, p&amp;lt;0.05) in CF ferret sections. Our findings suggest increased efficiency of proinsulin processing and a potential compensatory upregulation of insulin expression during this phase with the surprising finding of increased glucagon expression. Additional studies are underway to further characterize changes in islet hormone expression across each of the four described phases as well as potential cellular dedifferentiation patterns. Disclosure H. M. Ismail: None. R. G. Mirmira: Advisory Panel; Self; Hibercell Inc., Sigilon Therapeutics, Inc., Veralox Therapeutics, Employee; Spouse/Partner; Beta Bionics, Inc. C. Evans-molina: Advisory Panel; Self; Provention Bio, Inc., Consultant; Self; Dompe, Other Relationship; Self; Bristol-Myers Squibb Company, Nimbus Pharmaceuticals, Pfizer Inc. R. N. Bone: None.

716-P: Transition from Multiple Daily Injections (MDI) to Omnipod 5 Automated Insulin Delivery System Improves A1C in Type 1 Diabetes (T1D)

Many of those with T1D in the US use MDI as their insulin delivery method. Hybrid closed-loop (HCL) systems such as the Omnipod 5 System may improve glycemic outcomes and reduce treatment burden, however, these systems must be accessible to current MDI users. We performed a subgroup analysis of participants transitioning directly from MDI in the pivotal study of the Omnipod 5 System. Children (6-13.9 y) and adults (14-70 y) with T1D≥6 months and A1C<10% used the HCL system for 3 months at home, after a 14-d run-in phase of MDI as their standard therapy (ST). Primary efficacy endpoints were change in A1C and percent time with sensor glucose in target range (TIR, 70-180 mg/dL) during HCL compared with MDI. Thirteen children (mean±SD, age 11±2 y, T1D duration 4±2 y, A1C 7.7±1.0%, 77% CGM users) and 23 adults (age 38±13 y, T1D duration 16±12 y, A1C 7.4±0.9%, 91% CGM users) used MDI as ST. HCL use among children and adults improved TIR by 16.7±14.0% and 12.7±12.5%, and reduced A1C by 1.0±0.8% and 0.5±0.7%, respectively, compared with MDI (all p<0.05, Table). There were no episodes of severe hypoglycemia or diabetic ketoacidosis in this subgroup. Direct transition from MDI to the Omnipod 5 System is feasible and effective in reducing A1C and improving TIR in T1D. Most participants (97%) chose to continue HCL use during an extension phase, suggesting high acceptability of the system among MDI users.View largeDownload slideView largeDownload slide DisclosureV. Shah: Advisory Panel; Self; Medscape, Sanofi, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi, vTv Therapeutics. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. G. Aleppo: Consultant; Self; Dexcom, Inc., Insulet Corporation, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. B. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. D. Desalvo: Consultant; Self; Insulet Corporation, Research Support; Self; Insulet Corporation, Speaker’s Bureau; Self; Dexcom, Inc. I. B. Hirsch: Consultant; Self; Abbott Diabetes, Bigfoot Biomedical, Inc., Research Support; Self; Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Medtronic. S. A. Macleish: Advisory Panel; Self; Insulet Corporation. J. E. Pinsker: Advisory Panel; Self; Medtronic, Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. T. T. Ly: Employee; Self; Insulet Corporation. A. B. Criego: Consultant; Self; Bigfoot Biomedical, Inc., Other Relationship; Self; Sanofi, Research Support; Self; Abbott Diabetes, Eli Lilly and Company, Insulet Corporation, Medtronic. A. L. Carlson: Board Member; Self; JDRF, Other Relationship; Self; Medtronic, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Omnipod, Sanofi, UnitedHealth Group. A. Bhargava: Research Support; Self; Abbott, AbbVie Inc., Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Covance Inc., Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Gan & Lee Pharmaceuticals, Insulet Corporation, Janssen Research & Development, LLC, Madrigal Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Mylan N. V., Novo Nordisk, Quintiles, Sanofi, Senseonics, Senseonics, Tolerion, Inc., viking. B. W. Bode: Advisory Panel; Self; Eli Lilly and Company, Consultant; Self; Bigfoot Biomedical, Inc., Companion Medical, Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Abvance Therapeutics, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Dompe, Eli Lilly and Company, Eyenuk, Inc., Insulet Corporation, Jaeb Center for Health Research, Medtronic, Nova Biomedical, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanofi, Senseonics, Viacyte, Inc., vTv Therapeutics, Xeris Pharmaceuticals, Inc., Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; Self; AgaMatrix, Aseko, Inc., Glytec, LLC. S. A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc.FundingInsulet Corporation

100-LB: Infusion Set Survival and Performance during the Medtronic Extended-Wear Infusion Set (EWIS) Pivotal Trial

Objective: Most insulin infusion sets (ISs) are labeled for 2- or 3-days use. The Medtronic EWIS is designed to increase wear time up to 7 days. This study reports on EWIS survival and performance during the pivotal trial (ClinicalTrials.gov: NCT04113694).Method: This multi-center (15), single-arm, non-randomized, non-inferiority trial in 259 participants (18-80yrs) with T1D using the MiniMed™ 670G system (with Humalog™ or Novolog™ insulin) involved wearing a 2- or 3-day IS for 2 weeks (run-in) followed by 12 consecutive EWIS wears (study phase). The latter was worn for ≥174 hours or until set failure. Safety and performance (i.e., a priori target of <16% failure rate due to unexplained hyperglycemia) were evaluated. Exploratory analysis of glycemic control (e.g., A1C, sensor glucose and time spent at glucose ranges) and insulin use during 3-day IS and EWIS wear were also evaluated.Result: The EWIS survival rate was 74.8% versus the 67.7% rate of 2- or 3-day ISs (p<0.05). The EWIS rate was 77.8% when excluding inadvertent early removals. Glycemic control outcomes were improved during EWIS use (Table) and there were no episodes of EWIS-related severe hypoglycemia or DKA.Conclusion: The 7-day EWIS was safe and its performance was superior at ≥174 hours compared to the performance observed for 2- or 3-day infusion sets.View largeDownload slideView largeDownload slide DisclosureB. A. Buckingham: Advisory Panel; Self; Medtronic, Tolerion, Inc., Research Support; Self; Beta Bionics, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. B. Horowitz: Research Support; Self; Abbott Laboratories, BD, Celgene, Crinetics Pharmaceuticals, Gan & Lee Pharmaceuticals, Medtronic, Speaker’s Bureau; Self; AstraZeneca, Lilly Diabetes, Merck & Co., Inc., Novo Nordisk Inc. K. B. Kaiserman: Advisory Panel; Self; Medtronic, Consultant; Self; Medtronic, Employee; Self; MannKind Corporation, Research Support; Self; Medtronic, Speaker’s Bureau; Self; Medtronic, Stock/Shareholder; Self; MannKind Corporation. S. Huang: None. V. Chen: Employee; Self; Medtronic. G. Zhang: Employee; Self; Medtronic. S. Chattaraj: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic. R. Vigersky: Employee; Self; Medtronic. R. L. Brazg: Research Support; Self; Abbott Diabetes, Ascensia Diabetes Care, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., Roche Diagnostic USA, Senseonics. T. S. Bailey: Consultant; Self; Abbott Diabetes, LifeScan, Novo Nordisk, Sanofi, Research Support; Self; Abbott, Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Lexicon Pharmaceuticals, Inc., Livongo, Medtronic, Medtrum Technologies, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Self; BD, Medtronic, Sanofi. Y. C. Kudva: Research Support; Self; Dexcom, Inc. S. K. Garg: Advisory Panel; Self; Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Zealand Pharma A/S, Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Medtronic. G. Grunberger: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk. J. Thrasher: Advisory Panel; Self; Medtronic, Board Member; Self; Medtronic, Consultant; Self; Medtronic, Research Support; Self; Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Mylan N. V., Novo Nordisk, Sanofi, Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Medtronic, Sanofi. A. Cavale: Research Support; Self; Eli Lilly and Company, Medtronic. A. Bhargava: Research Support; Self; Abbott, AbbVie Inc., Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Boston Therapeutics, Inc., Covance Inc., Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Insulet Corporation, Janssen Research & Development, LLC, Kowa Pharmaceuticals America, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Mylan N. V., Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics.

717-P: Real-World, Patient-Reported Data on Training and Use of 670G Hybrid Closed-Loop (HCL) among Children and Adults with Type 1 Diabetes (T1D)

This report describes patient-reported data from persons with T1D initiating use of the Medtronic MiniMed 670G HCL insulin delivery system (670G) for clinical care. Questionnaires were completed in clinic before starting the system, and then follow up surveys were emailed at 6 weeks, 6 months and 12 months from the time of enrollment. Participants who completed the 6 week survey (n=97) had a mean HbA1c of 8.2%, T1D duration of 19 yrs, median age of 37 yrs, with 57% being female, 88% non-Hispanic white. Most were on pump therapy at baseline with 87% using a sensor. Nearly all who completed the training questionnaire agreed/strongly agreed that he/she received adequate training on the majority of the 670G components. Alarms were described as somewhat to very bothersome during the day by nearly half of participants/parents and more than half had issues with sleep interruption at night (Table). Close to half (~40%) noted frequent exits from Auto Mode were somewhat to very bothersome. In this real-world assessment of 670G use, while many were satisfied by device training, issues with the system were prevalent amongst those who persisted with device use. With this first in-class device, this study highlights that methods to minimize burdens of HCL use, such as the number of alarms and frequent exits from automation, will be essential for alternate and next generation systems.View largeDownload slideView largeDownload slide DisclosureC. Bauza: None. S. Dubose: None. A. Verdejo: None. R. Beck: Consultant; Self; Bigfoot Biomedical, Inc., Diasome Pharmaceuticals, Inc., Insulet Corporation, Lilly Diabetes, vTv Therapeutics, Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Medtronic, Novo Nordisk, Tandem Diabetes Care. R. M. Bergenstal: Advisory Panel; Self; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk, Onduo LLC., Roche , Sanofi, United Healthcare , Consultant; Self; Abbott Diabetes, Ascensia , Dexcom, Inc., Eli Lilly and Company, Hygieia, Johnson & Johnson, Medtronic, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare, Other Relationship; Self; HealthPartners Institute, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Helmsley Charitable Trust, Hygieia, Johnson & Johnson, Medtronic, NIDDK, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare. J. Sherr: Advisory Panel; Self; Cecelia Health, Insulet Corporation, Medtronic, Consultant; Self; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Speaker’s Bureau; Self; Lilly Diabetes.FundingThe Leona M. and Harry B. Helmsley Charitable Trust

1164-P: A Zebrafish Nonalcoholic Fatty Liver Disease Model Links Liver Inflammation with Pancreatic Inflammation and Hyperglycemia

The spectrum of nonalcoholic liver disease (NAFLD) ranges from simple steatosis to steatohepatitis with the latter having the potential to irreversibly progress to cirrhosis. Compared with the general population, NAFLD is more frequently seen in patients with type 2 diabetes (T2D), and conversely, NAFLD is associated with increased incidence of T2D. Existing rodent models of NAFLD focus narrowly on certain stages of liver damage and insufficiently encompass all metabolic changes, limiting their utility. The aims of this study were to develop a new model of NAFLD in young zebrafish and use it to probe the associations between liver inflammation and pancreatic islet function. We examined hepatopancreatic inflammation under three conditions: (1) in a zebrafish line (fabp10-CETI-PIC3) in which liver-specific expression of pro-inflammatory cytokines IL-1β, TNFα, and IFN-γ was induced by doxycycline treatment (M1); (2) in wild-type zebrafish fed a high-fat diet (M2); and (3) in a combination of these models (M3). All three conditions showed increased expression of inflammatory cytokines compared to Tg(fabp10:cre) control larvae, and when compared to controls, all three showed increased macrophage infiltration in the liver. Strikingly, staining with CellRox Deep Red to assess reactive oxygen species (ROS)-mediated stress in the liver revealed a 2-fold increase in the M3 combination model, but not in either M1 or M2. Further, although all models showed hyperglycemia, decreased insulin transcription without β cell death, and ROS accumulation in the pancreas, only the M3 condition demonstrated a significant increase in macrophage infiltration of the pancreatic islets as compared to controls. In sum, our novel zebrafish model of liver steatosis and steatohepatitis is a promising model in which to study the intricate associations between NAFLD and T2D, and may serve as an amenable platform for screening novel pharmaceutical interventions. Disclosure S. Ibrahim: None. I. Haider: None. A. Kulkarni: None. I. Doycheva: None. R. G. Mirmira: Advisory Panel; Self; Hibercell Inc., Sigilon Therapeutics, Inc., Veralox Therapeutics, Employee; Spouse/Partner; Beta Bionics, Inc. E. K. Sims: None. R. Anderson: None.

621-P: The Inaccuracy of Commercial Home Hemoglobin A1c Tests

The COVID-19 pandemic and rapid expansion of telemedicine has increased the need for accurate and reliable capillary A1c testing. Nevertheless, validation studies of commercially available kits have been in short supply. As such, capillary and venous A1c samples were assessed using 3 commercial home kits (Home Access, CoreMedica, A1cNow) and 2 non-commercial kits from academic centers (U of MN Advanced Research and Diagnostic Lab [ARDL] and Children’s Mercy Hospital [CMH]). Samples were collected either with study staff guidance (non-commercial) or hands-on assistance (commercial) and sent by USPS for processing except for the immediate response A1cNow+ kit. Differences in A1c between commercial kits and reference values were appreciable (Table). Notably, none of the commercially tested kits reached the National Glycohemoglobin Standardization Program target of more than 90% of values within 5% of DCCT venous reference values although the Home Access kit performed much better than the other two. In contrast, evaluation of kits from ARDL and CMH showed 97.4% of values within the 5% standard. Ease of use and discomfort with sample collection varied between kits. While the accuracy of the commercial kits analyzed was limited, participants’ response was positive overall. Telemedicine is likely to persist as a mainstay of diabetes care well after the COVID-19 era. As such, accurate home A1c testing represents an urgent need for the diabetes community.View largeDownload slideView largeDownload slide DisclosureL. M. Jacobsen: None. L. E. Bocchino: Other Relationship; Self; Leona M. and Harry B. Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. J. Adams: None. J. W. Lum: None. M. J. Haller: Board Member; Self; SAB Biotherapeutics, Inc., Consultant; Self; MannKind Corporation, Other Relationship; Self; Janssen Pharmaceuticals, Inc., Sanofi. R. Beck: Consultant; Self; Bigfoot Biomedical, Inc., Diasome Pharmaceuticals, Inc., Insulet Corporation, Lilly Diabetes, vTv Therapeutics, Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Medtronic, Novo Nordisk, Tandem Diabetes Care.