341-OR: Enhanced Responsiveness of ß- and α-Cells to Glucagon-Like Peptide-1 (GLP-1) in Youth vs. Adults with Impaired Glucose Tolerance (IGT) or Drug-Naïve Type 2 Diabetes (T2D)

Abstract

In the Restoring Insulin Secretion (RISE) Study, youth (Y) compared to adults (A) had enhanced β-cell (greater incremental C-peptide [CP] responses) and α-cell responsiveness (greater glucagon [GG] suppression) . As GLP-1 increases CP and decreases GG, we measured GLP-1 (Mercodia) during a 3-h oral glucose tolerance test (OGTT) in 65 Y (age: 14.2 y) and 65 A (51.0 y) to determine if greater GLP-1 release explained age-related differences in CP and GG responses. Groups were matched for sex (71% female) , race/ethnicity (29% white, 22% black, 37% Hispanic) and IGT/drug naïve T2D (80/20%) status and did not differ by BMI (36.7±6.0 vs. 35.3±4.1 kg/m2) . We calculated fasting, early (0-to-30 mins; ∆) and incremental area under the curve (iAUC) responses for G, CP and GLP-1, and decrements in GG (d∆; dAUC) . Y and A did not differ in fasting or OGTT glycemic responses, but Y had greater fasting CP, ∆CP and iAUC CP, more d∆GG suppression, and a trend for more diGG suppression, than A (Table) . Fasting GLP-1 was not different in Y vs. A, but stimulated GLP-1 was lower in Y throughout the OGTT. In conclusion, in Y higher CP and lower GG during an OGTT, paired with lower GLP-1 concentrations, suggest that the enhanced β- and α-cell responsiveness to GLP-1 could be due to increased sensitivity of the islet cells to the incretin, rather than a primary increase in GLP-1 release. Disclosure K.J.Nadeau: None. S.E.Kahn: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc. T.Consortium: None. A.H.Tjaden: None. D.A.Ehrmann: None. S.A.Arslanian: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Other Relationship; AstraZeneca, Research Support; Eli Lilly and Company, Novo Nordisk. S.Caprio: None. S.Edelstein: None. T.S.Hannon: Advisory Panel; Eli Lilly and Company. K.A.Temple: None. A.Xiang: None. Funding American Diabetes Association (1-20-RISE-01) ; NIDDK, Department of Veterans Affairs, and Kaiser Permanente Southern California