Increased β-Cell Responsivity Independent of Insulin Sensitivity in Healthy African American Adults

Background: Primary insulin hypersecretion predicts type 2 diabetes (T2DM) independent of insulin resistance. Enhanced beta-cell glucose responsivity contributes to insulin hypersecretion. African Americans (AAs) are at a higher risk for T2DM than non-Hispanic Whites (NHWs). Whether AAs manifest primary insulin hypersecretion is an important topic that has not been examined systematically. Objective: To examine if nondiabetic AA adults have a higher beta-cell glucose responsivity compared with NHWs. Methods: Healthy nondiabetic AA (n = 18) and NHW (n=18) subjects were prospectively recruited. Indices of beta-cell function, acute C-peptide secretion (X0); basal (Phi(B)), first-phase (Phi(1)), second-phase (Phi(2)), and total beta-cell responsivity to glucose (Phi(TOT)), were derived from modeling of insulin, C-peptide, and glucose concentrations during an intravenous glucose tolerance test. Insulin sensitivity was assessed by the hyperinsulinemic-euglycemic glucose clamp technique. Results: Glucose disposal rate (GDR) during clamp was similar in AAs and NHWs (GDR: [AA] 12.6 +/- 3.2 vs [NHW] 12.6 +/- 4.2 mg/kg fat free mass +17.7/min, P = .49). Basal insulin secretion rates were similar between the groups. AA had significantly higher X0 (4423 +/- 593 vs 1807 +/- 176 pmol/L, P = .007), Phi(1) [377.5 +/- 59.0 vs 194.5 +/- 26.6 (10(9)) P = 0.03], and Phi(TOT) [76.7 +/- 18.3 vs 29.6 +/- 4.7 (10(9)/min), P = 0.03], with no significant ethnic differences in Phi(B) and Phi(2). Conclusions: Independent of insulin sensitivity, AAs showed significantly higher first-phase and total beta-cell responsivity than NHWs. We propose that this difference reflects increased beta-cell responsivity specifically to first-phase readily releasable insulin secretion. Future studies are warranted to identify mechanisms leading to primary beta-cell hypersensitivity in AAs.