Results from hyperglycemic clamps in the Restoring Insulin Secretion (RISE) Study found that youth (10-19 y) with impaired glucose tolerance (IGT) or early type 2 diabetes (T2D) are more insulin resistant and secrete more insulin than adults (20-65 y), despite similar BMI. Here we use Mari modeling of RISE 3-h OGTT data to explore differences in β-cell function between youth and adults. The Mari model describes the relationship between insulin secretion rate (ISR) and glucose concentration. The slope of the relationship is β-cell glucose sensitivity (GS); ISR at a fixed glucose is also calculated. Derived terms include the 3-h to baseline potentiation factor ratio (PFR; a relative insulin secretion increase during the OGTT) and rate sensitivity (RS; the dependence of ISR on the glucose rate of change). Analysis of covariance was used to compare youth vs. adults, with secretion measures adjusted for insulin sensitivity (M/I) from hyperglycemic clamps. Adjusted GS was significantly higher in youth vs. adults with IGT but not in those with T2D. Adjusted RS and ISR at plasma glucose of 5 and 7 mmol/L were higher in youth vs. adults for both IGT and T2D. The PFR was lower in youth than adults, suggesting possible differences in either incretin effects or glucose potentiation. Our OGTT findings provide additional evidence that β-cells in youth are more responsive to glucose than adults, with reduced secretion parameters in those with T2D.
K. Utzschneider: Consultant; Self; Novo Nordisk Inc. A. Mari: Consultant; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim International GmbH. M. Tripputi: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. K.J. Nadeau: None. S. Edelstein: None. T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company. S.A. Arslanian: None. M. Cree-Green: None. T.A. Buchanan: Research Support; Self; Allergan, Apollo EndoSurgery. S. Caprio: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. R. Consortium: None.
American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases