Genetic risk score prediction of leg fat and insulin sensitivity differs by race/ethnicity in early pubertal children.

Abstract

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. 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. 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. 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). 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.