Endurance Training Improves Insulin Sensitivity, Metabolic Flexibility, and Mitochondrial Function in Type 2 Diabetes

To determine how endurance training influences insulin sensitivity, metabolic flexibility, and mitochondrial function in individuals with and without type 2 diabetes (T2D). Insulin sensitivity (2-step hyperinsulinaemic-isoglycaemic clamp), metabolic flexibility, and mitochondrial respiratory capacity and H₂O₂ emission were assessed in participants with T2D (n = 15) and controls (n = 14) before and after 12 weeks of supervised endurance training. Sensitivity analyses were performed using linear mixed-effects models including all available participants. At baseline, glucose clearance was lower in individuals with T2D compared with controls. Training increased glucose clearance (mL/min/kg FFM) in both groups, with larger model-derived improvements in T2D (Step 1: +1.43 [0.88-1.97]; Step 2: +3.18 [2.12-4.23]) than in controls (Step 1: +0.76 [0.21-1.31]; Step 2: +1.49 [0.53-2.45]). The group × time interaction was significant at the higher insulin step. Metabolic flexibility to fat-but not glucose-was reduced in T2D and improved modestly with training. Mitochondrial respiratory capacity did not differ between groups; however, training decreased mitochondria-specific respiration and H₂O₂ emission normalized to CS activity and respiration. Endurance training enhances insulin sensitivity and fat oxidation in individuals with T2D and induces favorable mitochondrial adaptations, despite the absence of intrinsic mitochondrial dysfunction.