Mitochondrial Bioenergetics and Skeletal Muscle Dysfunction in Type 2 Diabetes Mellitus: Novel Mechanistic Insights from a Nigerian Urban Cohort in Enugu

Skeletal muscle mitochondrial dysfunction is hypothesised to be a central but incompletely characterised mechanism driving insulin resistance and exercise intolerance in type 2 diabetes. This study investigated mitochondrial bioenergetics and their relationship to skeletal muscle dysfunction in a Nigerian type 2 diabetic cohort in Enugu, South East Nigeria, addressing a mechanistic gap with minimal African representation in global literature. A cross-sectional observational design with mechanistic depth enrolled 60 adults with confirmed type 2 diabetes and 30 age-matched healthy controls. Vastus lateralis muscle biopsies were obtained to assess mitochondrial enzyme activities including citrate synthase and complex I through IV of the electron transport chain. Skeletal muscle insulin signalling was evaluated through Akt and AS160 phosphorylation assays. In vivo muscle oxidative capacity was estimated by phosphocreatine recovery kinetics using near-infrared spectroscopy. Exercise capacity was assessed by VO2peak on a cycle ergometer. Mediation and moderation analyses were applied. Results showed significantly reduced mitochondrial enzyme activities across all complexes in diabetic patients. Phosphocreatine recovery was prolonged, confirming in vivo oxidative capacity impairment. Mitochondrial dysfunction severity was the strongest mediator of reduced VO2peak, independent of haemoglobin A1c. The study provides mechanistic evidence for mitochondrial pathology in Nigerian type 2 diabetic skeletal muscle, an original contribution to physiology. Mitochondrially targeted exercise and pharmacological interventions are proposed for future trials. Keywords: mitochondrial bioenergetics, type 2 diabetes, skeletal muscle, insulin resistance, Enugu.