Exaggerated insulin secretion in Pima Indians and African‐Americans but higher insulin resistance in Pima Indians compared to African‐Americans and Caucasians

AbstractAims  African‐Americans have a higher prevalence of Type 2 diabetes than Caucasians, but a lower prevalence than Pima Indians. Studies suggest that both African‐Americans and Pima Indians are more insulin resistant and have higher acute insulin secretory responses to glucose than Caucasians; however, a direct comparison between these three populations is lacking.Methods  We measured insulin secretory responses to intravenous glucose (acute insulin response, AIR, 25 g ivGTT); insulin action at physiological (M‐low) and supra‐physiological (M‐high) levels of hyperinsulinaemia (2‐step hyperinsulinaemic clamp); basal and insulin‐suppressed endogenous glucose production in 30 African‐Americans, 30 Pima Indians and 30 Caucasians with normal glucose tolerance who were carefully matched for age, sex, and body fat (hydrodensitometry or DEXA). A subgroup of 24 subjects from each group additionally underwent a standardized mixed meal test.Results  M‐low was lower in Pima Indians (0.50 ± 0.03) compared to Caucasians (0.59 ± 0.02, P = 0.02) and African‐Americans [0.58 ± 0.03 mg/kgEMBS/min, log10 (means ± SE), P = 0.03] but was not different between African‐Americans and Caucasians. Basal endogenous glucose production was lower in Pima Indians (2.43 ± 0.06) compared to African‐Americans (2.70 ± 0.06, P = 0.02) and was not different between Pima Indians and Caucasians (2.59 ± 0.09 mg/kgEMBS/min) or African‐Americans and Caucasians (all P > 0.18). Insulin‐suppressed endogenous glucose production during the clamp was not different among the groups (all P > 0.40). AIR was higher in both African‐Americans (13.51 ± 0.26) and Pima Indians (13.72 ± 0.27) compared to Caucasians (12.33 ± 0.25 pm, log10, both P < 0.01). The areas under the curve for glucose in response to the oral glucose tolerance test and mixed meal test were higher in Pima Indians compared to African‐Americans (P = 0.03 and P = 0.03, respectively) and Caucasians (P = 0.01, mixed meal test), but not different between African‐Americans and Caucasians.Conclusions  Exaggerated glucose‐stimulated insulin secretion, manifested initially as an increased response to an intravenous glucose challenge, appears to be a characteristic in people with normal glucose tolerance at higher risk for diabetes. Lower whole‐body insulin sensitivity in Pima Indians compared to African‐Americans, however, may contribute to the higher risk for Type 2 diabetes in Pima Indians compared to African‐Americans.