We derived β-cell measures compensating for insulin resistance (disposition indices [DI]) from two-step hyperglycemic clamps with arginine stimulation, and examined their associations with glycemia cross-sectionally and longitudinally after treatment. Data included 355 adults (age 23-66 y; 51% female) and 89 youth (age 10-19 y; 71% female) from the RISE Consortium studies. Clamps were done at baseline and after 12 mo treatment with medications or gastric banding. Insulin sensitivity was quanitfied as M/I. β-cell responses included acute insulin (AIRg) and C-peptide (ACPRg) responses to glucose; steady-state C-peptide (SSCP) at glucose ∼11.1 mmol/L; and maximum insulin (AIRmax) or C-peptide (ACPRmax) responses to arginine at glucose >25 mmol/L. DIs were calculated from M/I and β-cell responses as [responses x (M/I)-b ]. The Table shows the correlations between each DI and glucose at baseline, and changes after treatment. The correlations were higher in youth than adults, except for changes in AIRmax or ACPRmax and 2-hour glucose. The correlations for ACPRg and AIRg were generally higher, followed by SSCP and then maximal responses. Thus, in the RISE cohorts, measures of early β-cell response were more strongly associated with glycemia than were late responses, with stronger correlations in youth. This underscores different contributions of early and late insulin secretion in the regulation of glycemia.
A. Xiang: None. T.S. Hannon: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. E. Barengolts: None. M. Cree-Green: Advisory Panel; Self; Novo Nordisk Inc. K.J. Nadeau: None. S. Sam: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T.A. Buchanan: None. T. Consortium: None.
American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases