Insulin sensitivity in African-American children with and without family history of type 2 diabetes

OBJECTIVE - African-Americans are at increased risk for type 2 diabetes. We have previously demonstrated that African-American children are hyperinsulinemic and insulin resistant compared with their white American peers. The aim of the present investigation was to assess the impact of family history of type 2 diabetes on insulin sensitivity in African-American children. RESEARCH DESIGN AND METHODS - A total of 13 prepubertal healthy children with negative family history (FH-) and 9 with positive family history (FH+) of type 2 diabetes underwent a 3-h hyperinsulinemic (40 mU . m(-2) . min(-1))-euglycemic clamp study to assess insulin sensitivity. The groups were comparable for age, pubertal status, total body adiposity determined by dual-energy X-ray absorptiometry, abdominal adiposity assessed by computed tomography scan at the level of L4-5 lumbar vertebra, and physical fitness measured by maximal oxygen consumption (VO2max). RESULTS - The FH+, compared with the FH-, group had lower insulin-stimulated glucose disposal (10.9 +/- 1.2 vs. 14.2 +/- 0.9 mg . kg(-1) . min(-1), P = 0.035) and lower nonoxidative glucose disposal (5.7 +/- 0.8 vs. 8.3 + 0.6 mg . kg(-1) . min(-1), P = 0.015), with no differences in rates of glucose oxidation, fat oxidation, or insulin-mediated free fatty acid suppression. Fasting hepatic glucose production assessed with [6,6-H-2(2)]glucose and basal rates of glucose and fat oxidation were not different between the two groups. CONCLUSIONS - These data suggest that in African-American children, family history of type 2 diabetes is a risk factor for insulin resistance. These children manifest important metabolic alterations, including impaired insulin-stimulated total and nonoxidative glucose disposal early in the first decade of life. We propose that this familial tendency, combined with environmental influences, could lead to type 2 diabetes decades later.