Introduction and Objective: Many people living with T1D do not achieve glycemic targets, and the risk of severe hypoglycemia persists. HDV-L restores postprandial hepatic glycogen storage by presenting insulin to hepatocyte receptors as a dense molecular aggregate, improving receptor signaling. The OPTI-2 study evaluated the impact of HDV-L on A1C and hypoglycemia risk.Methods: In a […]
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1238-OR: Pioglitazone Prevents the Blunted Counterregulatory Response Induced by Recurrent Hypoglycemia
Introduction and Objective: Recurrent iatrogenic hypoglycemia blunts the counterregulatory response (CRR) to hypoglycemia. This study tested the hypothesis that RH induces insulin resistance and that the insulin sensitizer, pioglitazone, prevents the development of insulin resistance and consequently prevents the development of a blunted epinephrine response to hypoglycemia.Methods: 8-10-week-old rats were randomized to 1 of 3 […]
Read More1258-OR: Performance of a Next-Generation Algorithm for Omnipod in Adults with Type 2 Diabetes: Findings from the STRIVE Randomized Trial
Introduction and Objective: A recent randomized crossover trial compared a next-generation algorithm for Omnipod (Omnipod 6) with the first-generation Omnipod® 5 Automated Insulin Delivery System in a diverse population of adults (T1D/T2D) and children (T1D). Assessing performance of Omnipod 6 in those with T2D is needed given the unique pathophysiology, insulin needs, and concomitant therapy […]
Read More1225-OR: Efficacy and Safety of Mazdutide 9 mg in Chinese Adults with Obesity: Results from the Phase 3 GLORY-2 Trial
Introduction and Objective: To evaluate the efficacy and safety of mazdutide (MAZ) 9 mg, a once-weekly GLP-1 and glucagon receptor dual agonist, in Chinese adults with obesity.Methods: In this randomized, double-blind, placebo (PBO)-controlled trial (NCT06164873, GLORY-2), 462 Chinese adults with obesity (BMI ≥30 kg/m2; 16.0% with T2D) were randomized in a 2:1 ratio to receive […]
Read More1237-OR: A Novel Hypoglycemic Clamp Procedure to Assess “Spontaneous Time to Recovery” as a Clinically Relevant Safety Endpoint
Introduction and Objective: The conventional hypoglycemic clamp utilizes high-dose IV insulin at fixed rates to induce target hypoglycemia, lacks standardized protocols and results in insulin overdose affecting spontaneous recovery. This improved hypoglycemic clamp procedure adjusts for individual insulin sensitivity and assesses “time to spontaneous recovery” as a critical endpoint.Methods: 12 healthy (41±12 yrs, 28±2 kg/m2) […]
Read More1270-OR: Differential Sorting of Immunomodulatory Islet Extracellular Vesicle Cargo Tracks with Heterogeneity in Beta-Cell Survival in Type 1 Diabetes
Introduction and Objective: We have shown that beta cell-derived extracellular vesicle (EV) programmed death ligand-1 (PD-L1) reduces CD8+ T-cell activity and may protect against beta cell killing in T1D. However, underlying mechanisms linking differences in islet EV cargo to heterogeneity in beta cell survival are poorly defined.Methods: EVs were isolated using size exclusion chromatography from […]
Read More1253-OR: ADA Presidents' Select Abstract: Efficacy and Safety of Orforglipron vs. Placebo Added to Titrated Insulin Glargine in Adults with Long-Standing Type 2 Diabetes: ACHIEVE-5
Introduction and Objective: The efficacy and safety of the daily oral, non-peptide GLP-1RA orforglipron (OFG) were assessed as add-on to insulin glargine with/without metformin and/or SGLT-2 inhibitors in adults with type 2 diabetes (T2D) (ACHIEVE-5; NCT06109311).Methods: In this 40-week double-blind, randomized, placebo-controlled, phase 3 study, participants with T2D and inadequate glycemic control were randomized (1:1:1:1) […]
Read More1275-OR: Central Regulation of Glucose Production Is Affected by Insulin Levels
Introduction and Objective: Central KATP channel activation with diazoxide (DZX) suppresses endogenous glucose production (EGP) in rodents and humans (JCI 121:4916, 2011), suggesting that brain signals help regulate glucose metabolism. This regulation may require adequate insulin levels (Diabetes 60:3132, 2011). Since previous studies were performed at insulin levels ~20 µU/ml, we evaluated this regulation under […]
Read More1274-OR: Effects of Empagliflozin on Hepatic Glucose Production, Gluconeogenesis, and Lipolysis in Type 2 Diabetes
Introduction and Objective: We previously showed that SGLT2 inhibitors stimulate endogenous glucose production, offsetting their glucosuria-induced glucose lowering action, and that this effect is not explained by changes in plasma glucose, insulin, or glucagon concentration using a pancreatic clamp. To investigate the impact of Empagliflozin (an SGLT2 inhibitor) on fasting hepatic glucose production (HGP), gluconeogenic […]
Read More1260-OR: Fully Closed-Loop Delivery of Ultra-Rapid Insulin Lispro and Pramlintide vs. Carbohydrate Counting in Type 1 Diabetes: A Randomized, Crossover, Noninferiority Trial
Introduction and Objective: Carbohydrate counting remains a major burden in type 1 diabetes. We evaluated a novel fully closed-loop (FCL) insulin-and-pramlintide delivery system designed to eliminate carbohydrate counting.Methods: We conducted a randomized, crossover, noninferiority trial assessing 21 days of (i) hybrid closed-loop (HCL) insulin-and-placebo delivery with carbohydrate counting and FCL insulin-and-pramlintide delivery at (ii) an […]
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