Race Adiposity Interactions Regulate Mechanisms Determining Insulin Sensitivity

Insulin resistance plays a major role in the etiology of chronic metabolic diseases, many of which differ with race/ethnicity. Previous studies using mainly indirect methods suggest that insulin sensitivity is lower in AA vs. EA. Our preliminary data using the reference standard glucose clamp indicate that in lean individuals, insulin sensitivity is lower among AA, while in obese individuals, insulin sensitivity is higher among AA. We hypothesize that this race/body mass index (BMI) interaction may be explained in part by significantly lower visceral and hepatic fat accumulation in AA. Conversely, based on our preliminary data, we hypothesize that inherently greater oxidative stress impairs insulin sensitivity even in AA, explaining lower insulin sensitivity in lean AA vs. EA. We propose to test these hypotheses by prospectively comparing skeletal muscle and hepatic insulin sensitivity in healthy lean, overweight, and obese AA and EA using the hyperinsulinemic isoglycemic glucose clamp. Analysis of ancestral genes will permit simultaneous assessment of the contribution of ancestry to main outcomes.