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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00428987.

Keywords: African Americans; insulin sensitivity; β-cell function.

Published by Oxford University Press on behalf of the Endocrine Society 2020.

Figures

Figure 1.

Hyperinsulinemic euglycemic glucose clamp studies in AA and NHW subjects. Data shown are the mean ± SEM for blood glucose concentration and glucose infusion rate plotted as a function of time.

Figure 2.

Plasma levels of glucose (A), insulin (B), and C-peptide (C), in adult African Americans (AA) and non-Hispanic Whites (NHW) during an insulin-modified intravenous glucose test (IM-FSIVGT). Data shown are mean ± SEM. P values for the effects of racial group, time, and the race*time interaction were obtained with repeated-measures analysis of variance with post hoc Bonferroni’s test.

Figure 3.

Model estimates of β-cell function during an insulin-modified intravenous glucose test. X0 (A), Φ Basal (B), Φ 1 (C), Φ 2 (D), and Φ Total (E) in adult African Americans (AA) and non-Hispanic Whites (NHW). Data shown are mean ± SEM. Comparisons between groups were assessed by independent unpaired t-test or The Wilcoxon-Mann-Whitney test.