Abstract
BACKGROUND: In the United States, the underlying reasons for racial/ethnic disparities in type 2 diabetes risk remain unclear. However, differences in genetic risk for insulin resistance and peripheral adipose tissue distribution may be contributing factors. OBJECTIVE: To investigate racial/ethnic differences in associations of genetic risk for insulin resistance with leg fat and insulin sensitivity in a cohort of American children. METHODS: Participants were healthy European-American (n = 83), African-American (n = 79) and Hispanic-American (n = 74) children aged 7-12 years. Genetic risk scores were derived from published variants associated with insulin resistance phenotypes in European adults. Body composition was assessed using dual-energy X-ray absorptiometry. Insulin sensitivity was determined from the frequently sampled intravenous glucose tolerance test and minimal modelling. Statistical models were adjusted for age, sex, pubertal stage and body composition. RESULTS: In the combined cohort, risk score was inversely associated with insulin sensitivity (p = 0.033) but not leg fat (p = 0.170). Within Hispanic Americans, risk score was inversely associated with insulin sensitivity (p = 0.027) and leg fat (p = 0.005), while associations were non-significant in European and African Americans (p > 0.200). CONCLUSIONS: The higher type 2 diabetes risk observed among Hispanic Americans may have a genetic basis related to an inability to store lipid in peripheral adipose tissue.