Using genetic admixture to explain racial differences in insulin-related phenotypes.

Documented differences in measures of insulin secretion and action between African Americans and European Americans may be due to either genetic or environmental factors. This study used genetic admixture (ADM), determined from approximately 20 ancestry informative markers, and a questionnaire designed to assess socioeconomic status (SES) to examine potential genetic and environmental contributions to minimal model-derived measures of insulin sensitivity (S(I)), fasting insulin, and the acute insulin response to glucose (AIR(g)) in 125 children residing in Birmingham, Alabama. The study was longitudinal in design and yielded multiple outcome measures on each subject. Mixed models analysis was used to determine if ADM and SES were independently related to S(I), fasting insulin, and AIR(g) after adjusting for confounding factors (pubertal status, adiposity, age) and for repeated testing of individuals. In this cohort, African ADM ranged from 0% (individuals with no markers reflecting African ancestry) to 100% (individuals with all 20 markers reflecting African ancestry). Results indicated that ADM was independently related to S(I) (P < 0.001) and fasting insulin (P < 0.01), with individuals having greater African ADM having a lower S(I) and a higher fasting insulin concentration. Both ADM (P < 0.001) and SES (P < 0.05) were independently related to AIR(g); children with greater African ADM or lower SES had a higher AIR(g), even after adjusting for S(I). These observations suggest that use of ADM can replace assignment of individuals to categorical racial groups; that lower S(I) and higher fasting insulin among African Americans compared with European Americans may have a genetic basis; and that higher AIR(g) among African Americans may be due to both genetic factors and to environmental factors that remain to be identified.