1794-P: Successful Standardization of a Hyperglycemic Clamp Method across Multiple Clinical Centers in the Restoring Insulin Secretion (RISE) Study

Abstract

In RISE, repeated measurements of β-cell function and insulin sensitivity were performed using a standardized hyperglycemic glucose clamp method. After in person training, clamps were performed at seven centers, in youth (Y) and adults (A) with impaired glucose tolerance (IGT) or early type 2 diabetes (T2D). The goal was to achieve and maintain a plasma glucose concentration of 200 mg/dL over 120 minutes using a priming bolus followed by a continuous infusion of 20% dextrose adjusted based on plasma glucose measured every 5 minutes. Guidance for achieving target glycemia was formalized using spreadsheet-based calculations for glucose boluses and infusion rate changes, using participant weight and the delta of glucose from 200 mg/dL. We evaluated the achieved bedside glucose relative to target as well as differences between the guidance and selected infusion rates. We also compared relevant subgroups. Data from 923 clamps performed on 379 participants (up to three clamps each) were examined. Overall mean ± SD plasma glucose 10 minutes after the glucose bolus was 189 ± 18 mg/dL. This was higher in Y vs. A (194 ± 20 vs. 188 ± 18, p<0.01) and higher in T2D vs. IGT (192 ± 18 vs. 188 ± 18, p<0.01). At steady state (100-120 minutes) the achieved glucose was 199 ± 8 mg/dL slightly but significantly higher in T2D vs. IGT (200 ± 7 vs. 198 ± 8, p=0.006) and in Y vs. A (200 ± 8 vs. 198 ± 8, p<0.05). The glucose infusion rate guidance was followed overall, but deviations occurred during the first 10 minutes (rate 11 ± 21 mL/hr higher than guidance). This deviation differed by clinic (p<0.01) and by diabetes status (p<0.01), but not in Y vs. A (p=0.26). Deviations from guidance were otherwise minor (2-4 mL/hr) and equal by subgroups except at T=90 min (A > Y p=0.05, IGT > T2D p<0.01). The RISE hyperglycemic clamp procedure used formalized calculations and guidance to standardize the clamp approach. This approach achieved uniformity in performance of glucose clamps in a multicenter study in both Y and A. Disclosure K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. A.H. Tjaden: None. S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. K. Utzschneider: Other Relationship; Self; Medtronic. S. Caprio: None. K. Utzschneider: Other Relationship; Self; Medtronic. K.M. Atkinson: None. M. Cree-Green: Advisory Panel; Self; Novo Nordisk Inc. K.J. Nadeau: None. T.A. Buchanan: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases