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 β-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 β-cell glucose responsivity compared with NHWs.

Methods: Healthy nondiabetic AA (n = 18) and NHW (n=18) subjects were prospectively recruited. Indices of β-cell function, acute C-peptide secretion (X0); basal (Φ B), first-phase (Φ 1), second-phase (Φ 2), and total β-cell responsivity to glucose (Φ 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), Φ 1 [377.5 ± 59.0 vs 194.5 ± 26.6 (109) P = 0.03], and Φ TOT [76.7 ± 18.3 vs 29.6 ± 4.7 (109/min), P = 0.03], with no significant ethnic differences in Φ B and Φ 2.

Conclusions: Independent of insulin sensitivity, AAs showed significantly higher first-phase and total β-cell responsivity than NHWs. We propose that this difference reflects increased β-cell responsivity specifically to first-phase readily releasable insulin secretion. Future studies are warranted to identify mechanisms leading to primary β-cell hypersensitivity in AAs.