Sex and race contribute to variation in mitochondrial function and insulin sensitivity

Abstract Objective Insulin sensitivity is lower in African American (AA) versus Caucasian American (CA). We tested the hypothesis that lower insulin sensitivity in AA could be explained by mitochondrial respiratory rates, coupling efficiency, myofiber composition, or H2O2 emission. A secondary aim was to determine whether sex affected the results. Methods AA and CA men and women, 19–45 years, BMI 17–43 kg m2, were assessed for insulin sensitivity (SIClamp) using a euglycemic clamp at 120 mU/m2/min, muscle mitochondrial function using high‐resolution respirometry, H2O2 emission using amplex red, and % myofiber composition. Results SIClamp was greater in CA (p < 0.01) and women (p < 0.01). Proportion of type I myofibers was lower in AA (p < 0.01). Mitochondrial respiratory rates, coupling efficiency, and H2O2 production did not differ with race. Mitochondrial function was positively associated with insulin sensitivity in women but not men. Statistical adjustment for mitochondrial function, H2O2 production, or fiber composition did not eliminate the race difference in SIClamp. Conclusion Neither mitochondrial respiratory rates, coupling efficiency, myofiber composition, nor mitochondrial reactive oxygen species production explained lower SIClamp in AA compared to CA. The source of lower insulin sensitivity in AA may be due to other aspects of skeletal muscle that have yet to be identified