Introduction and Objective: Insulin secretion in nondiabetic individuals is inversely related to the prevailing level of insulin sensitivity. The aim of the present study was to characterize insulin secretion caused by GLP-1 RA in non diabetic individualsMethods: 251 subjects free of T2DM received a 2-step hyperglycemic clamp (+125 mg/dl, and +400 mg/dl) followed by intravenous exenatide infusion and 5-grms intravenous arginine injection. Insulin sensitivity was measured with the Matsuda index and the euglycemic insulin clamp.Results: exenatide infusion caused a robust increase (41%) in plasma C-peptide concentration and the increase in plasma C-peptide concentration was significantly greater in NGT subjects (57%) than in subjects with IFG and/or IGT (39%), (p=0.007). However, unlike the increase in insulin secretion caused by hyperglycemia, the increase in insulin secretion caused by exenatide infusion was unrelated to insulin sensitivity or to the increase in insulin secretion cause by glucose.Conclusion: incretin-stimulated insulin secretion is unrelated to the prevailing level of insulin sensitivity and is impaired in subjects with prediabetes.
M. Abu-Farha: None. A. Chavez: None. G. Baskoy: None. J.M. Adams: None. J. Abubaker: None. T. Alessa: Advisory Panel; Abbott Diagnostics. Speaker’s Bureau; Amgen Inc, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Merck & Co., Inc, Novo Nordisk, Sanofi. F. Alajmi: Advisory Panel; Abbott. Research Support; Novo Nordisk. Speaker’s Bureau; Novo Nordisk. R. Belfort De Aguiar: None. R.A. DeFronzo: Advisory Panel; AstraZeneca. Research Support; AstraZeneca. Speaker’s Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Research Support; Boehringer-Ingelheim. Advisory Panel; Corcept Therapeutics, Novo Nordisk. Speaker’s Bureau; Corcept Therapeutics. Research Support; 89bio, Inc, Amgen Inc. F. Almulla: None. M. Abdul-Ghani: None.
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