Sex and Diabetes Status Interact to Affect Human Skeletal Muscle Mitochondrial Function

People with type 2 diabetes (T2D) have lower cardiorespiratory fitness (CRF)–a predictor of cardiovascular disease, morbidity, and mortality–than those without T2D. The impact of diabetes on CRF is greater in females than males. T2D confers worse CRF, in part, due to impairments in mitochondrial function, but it is unclear to what extent sex and T2D attenuate the expected improvements in mitochondrial function due to exercise training (ExTr). We hypothesized that female sex and T2D decrease mitochondrial response to ExTr. Mitochondrial respiration measures in vastus lateralis of physically inactive overweight adults aged 30-55 years with and without T2D were analyzed pre- and post- ExTr. We found increases in state 3 respiration (p=0.01), state 4 respiration (p=0.0002), and uncoupled respiration (p=0.02) after ExTr in all groups, suggesting a consistent effect of ExTr. Sex and T2D status interact to affect state 3 respiration (p=0.0003), State 4 respiration (p=0.003) and oxidative phosphorylation (P/E) ratio (p=0.0002) (Figure); females with T2D have lower mitochondrial respiration than males with T2D, unlike overweight control participants. Sex and T2D did not statistically interact with ExTr. These findings suggest that differences in muscle mitochondrial function due to T2D and sex persist despite improvements in mitochondrial respiration with ExTr. Disclosure L.Abushamat: None. J.G.Regensteiner: None. R.L.Scalzo: None. I.E.Schauer: None. L.Knaub: None. D.Rafferty: None. E.Clark: None. M.O.Whipple: None. A.G.Huebschmann: None. J.E.B.Reusch: Advisory Panel; Medtronic. Funding American Diabetes Association (1-21-CMF-003 to L.A.); U.S. Department of Veterans Affairs (CX001532)