Insulin Sensitivity in African-American Children with and without Family History of Type 2 Diabetes

Abstract 501 Endocrinology I Poster Symposium, Saturday, 5/1

Epidemiological evidence suggests that the risk to develop Type 2 diabetes is genetically determined. African-Americans are at increased risk for Type 2 diabetes. Moreover, over the last decade there has been an alarming increase in the rate of obesity-related Type 2 diabetes in adolescents with a propensity in Blacks. We had previously demonstrated that African-American children are hyperinsulinemic and insulin resistant compared with their White-American peers. ( J Pediatr 129:440, 1996; J Clin Endocrinol Metab 82:1923, 1997). The aim of the present investigation was to assess the impact of family history of Type 2 diabetes on insulin sensitivity and secretion in African-American children. Thirteen prepubertal healthy children with negative family history (FH(-)) and 9 with positive family history (FH(+)) for Type 2 diabetes were studied. The groups were matched for age (9.9±0.2 and 10.0±0.3 yrs, respectively), pubertal status (Tanner I), total body adiposity determined by DEXA, abdominal adiposity assessed by CT scan at the level of L_4-5 lumbar vertebra, and physical fitness measured by maximal oxygen consumption (VO_2max). During a 3-hour hyperinsulinemic (40 mu/m²/min)-euglycemic clamp, the FH(+) compared with FH(-) group had lower insulin stimulated glucose disposal (10.9±1.2 vs 14.2±0.9 mg/kg/min, p=0.035), and lower non-oxidative glucose disposal (5.7±0.8 vs 8.3±0.6 mg/kg/min, p=0.015) with no differences in rates of glucose oxidation, fat oxidation, and insulin mediated free fatty acid suppression. Fasting hepatic glucose production (3.3±0.3 and 3.7±0.5 mg/kg/min), assessed with [6,6-²H₂]glucose, and basal rates of glucose and fat oxidation were not different between the two groups. During a 2-hour hyperglycemic clamp (225 mg/dl), first-phase and second-phase insulin levels were not different between the two groups.

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. Therefore, in high risk populations early intervention with lifestyle changes should be implemented in childhood.