1261-P: OGTT Model–Derived ß-Cell Function Reveals Differential Loss in Youth vs. Adults during and following Treatment Withdrawal in the Restoring Insulin Secretion (RISE) Study

Loss of β-cell function is critical in the pathogenesis of T2D and may progress more rapidly in youth. We compared 3-hr OGTT model-derived measures of β-cell function in youth and adults with IGT or T2D in RISE treated for 12 mo with metformin (MET), or glargine followed by metformin (G/M) and 9 mo after treatment withdrawal. Model parameters included insulin sensitivity (OGIS), insulin secretion rate (ISR) at glucose 6.5 mM (ISR-6.5), total ISR (tISR), glucose sensitivity (GS: slope ISR vs. glucose concentration) and rate sensitivity (RS: ISR relative to glucose rate of change). Linear mixed models tested for differences by time (0-12 and 0-21 mo), age (youth vs. adults) and treatment (MET vs. G/M). Key observations included the following. Insulin sensitivity (OGIS) increased transiently in all but adults on G/M. In youth, insulin secretion (ISR-6.5 and tISR) and RS decreased relative to baseline, with GS also decreased in the G/M arm. In contrast, in adults there were no significant changes in modeled parameters at 21 mo. Insulin secretion and β-cell function parameters decreased more in youth vs. adults in the G/M arm. By treatment, GS decreased more in the G/M vs. MET arm in youth, but there were no differences in adults. In conclusion, only youth exhibited worsening of features of β-cell function that can only be derived with mathematical modeling. Disclosure K. Utzschneider: Other Relationship; Self; Medtronic. M. Tripputi: None. M. Cree-Green: Advisory Panel; Self; Novo Nordisk Inc. T.S. Hannon: None. K.J. Nadeau: None. E. Barengolts: None. J.P. Palmer: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S. Caprio: None. S. Edelstein: None. A. Mari: Consultant; Self; Lilly Diabetes. Research Support; Self; Boehringer Ingelheim International GmbH. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01); National Institute of Diabetes and Digestive and Kidney Diseases