Although obesity is a significant public health problem, why obesity leads to diabetes in some individuals but not others is poorly understood. Mitochondrial impairment, particularly in skeletal muscle with its high energy requirement, has been implicated in the pathogenesis of obesity-related insulin resistance. In addition, individuals with genetic disorders affecting mitochondrial function are at increased risk of diabetes. The proposed studies will investigate the association between skeletal muscle oxidative phosphorylation capacity (OXPHOS), which is a dimension of mitochondrial function, and glucose and lipid homeostasis in (i) individuals with genetic disorders of muscle mitochondrial function as compared to (ii) non-obese adults and (iii) otherwise healthy obese adults.