Effects of Treatment of Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes With Metformin Alone or in Combination With Insulin Glargine on β-Cell Function: Comparison of Responses In Youth And Adults

beta-Cell dysfunction is central to the pathogenesis of impaired glucose tolerance (IGT) and type 2 diabetes. Compared with adults, youth have hyperresponsive beta-cells and their decline in beta-cell function appears to be more rapid. However, there are no direct comparisons of beta-cell responses to pharmacological intervention between the two age-groups. The Restoring Insulin Secretion (RISE) Adult Medication Study and the RISE Pediatric Medication Study compared interventions to improve or preserve beta-cell function. Obese youth (n = 91) and adults (n = 132) with IGT or recently diagnosed type 2 diabetes were randomized to 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin. Hyperglycemic clamps conducted at baseline, after 12 months of medication, and 3 months after medication withdrawal assessed beta-cell function as steady-state and maximal C-peptide responses adjusted for insulin sensitivity. Temporal changes in beta-cell function were distinctly different. In youth, beta-cell function deteriorated during treatment and after treatment withdrawal, with no differences between treatment groups. In adults, beta-cell function improved during treatment, but this was not sustained after treatment withdrawal. The difference in beta-cell function outcomes in response to medications in youth versus adults supports a more adverse trajectory of beta-cell deterioration in youth.