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.

Ethnic differences in beta cell function occur independently of insulin sensitivity and pancreatic fat in black and white men

“… 68 This may be explained by different responses to glucose in BA men and women, with studies consistently finding greater hyperinsulinemia in women. 55 69–72 We note with interest that in a recent investigation by Armiyaw et al 15 it was only the African-American women who contributed to ethnic differences observed in beta cell responsivity, not the men. As their study was neither designed nor powered to examine interactions by sex, Armiyaw et al 15 rightly advised caution when interpreting these findings.…”

“… 55 69–72 We note with interest that in a recent investigation by Armiyaw et al 15 it was only the African-American women who contributed to ethnic differences observed in beta cell responsivity, not the men. As their study was neither designed nor powered to examine interactions by sex, Armiyaw et al 15 rightly advised caution when interpreting these findings. Further work examining the interactions between sex and ethnicity in BA groups is warranted.…”

Minimal Model–Derived Insulin Sensitivity Index Underestimates Insulin Sensitivity in Black Americans

“…Participants were admitted for a 3-night visit to the National Institutes of Health Metabolic Research Unit. After an overnight fast, S I was evaluated by the EHC (glucose disposal rate [GDR]) and insulin-modified FSIVGTT (S I -MM) on different days in random order as previously described ( 4 ). The rate of glucose disposal ( M ), a measure of S I was defined as the average of the glucose infusion rate during the steady state (GDR in milligrams per minute) corrected for estimated metabolic body size.…”

“…The steady-state period of the clamp was defined as a ≥20-min period, 90 min after the initiation of the clamp, where the coefficient of variation for plasma glucose and glucose infusion rate was <5%. Prior to EHC, basal hepatic glucose production (HGP) and hepatic insulin resistance index were measured by using a stable isotope tracer ( 4 ). Because of the interruption in pharmacy compounding services and access to tracers, we could conduct tracer studies in only 43 individuals (BA n = 21; NHW n = 22).…”

“…In addition, we measured circulating IGF binding protein 1 (IGFBP-1), a marker for hepatic S I . Minimal model analysis of the FSIVGTT was used to estimate glucose effectiveness (Sg) and S I -MM values as previously described using MINMOD software (version 6.02) (MinMOD Millenium, Los Angeles, CA) ( 4 ). Precision of parameter estimates from S I -MM was assessed by fractional SD.…”