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

Aims 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, log(10) (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, log(10), 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.