Sustained improvement of mitochondrial respiration after high intensity interval training in patients with type 2 diabetes and healthy controls probably results from increased mitochondrial biogenesis

 

High intensity interval training (HIT) has been proposed to stimulate mitochondrial biogenesis in healthy populations. We hypothesized that HIT would increase skeletal muscle insulin sensitivity due to improved muscle mitochondrial function in type 2 diabetes (T2D) patients and age- and BMI-matched controls (CON). We examined 12 sedentary male patients with T2D and 12 healthy male CON (age: 58 ± 5 vs. 57 ± 4 years, BMI: 31.4 ± 2.4 vs. 30.4 ± 2.3 kg/m²) that were enrolled in a 12-week HIT cycling protocol. Hyperinsulinemic-euglycemic clamps, skeletal muscle biopsies for high resolution respirometry and magnetic resonance spectroscopy for liver fat quantification were performed. After 12 weeks of HIT, T2D had increased their insulin sensitivity (in mg/kg.min; 3.9 ± 1.9 vs. baseline: 2.7 ± 1.6, p = 0.02), which returned to baseline after detraining. In CON, insulin sensitivity was increased by 20% following one exercise bout, but not after 12 weeks (8.0 ± 1.7 vs. baseline: 6.6 ± 2.6, p = 0.23). In T2D, liver fat was decreased by 17% and remained decreased after detraining. CON had lower liver fat content at baseline (CON: 4.8 ± 3.7% vs. T2D: 15.2 ± 7.8, p = 0.003), which remained unchanged by the training period. Muscle maximal uncoupled respiration increased in T2D and CON by 44% and 48%, respectively, at 12 weeks and remained increased after detraining (p < 0.01). Improvements in mitochondrial respiration were abolished after correction for citrate synthase activity (CSA) in both groups. We conclude that HIIT training improved insulin sensitivity and liver fat content in patients with T2D and that the improvement in muscle mitochondrial oxidation rather results from mitochondrial biogenesis than from altered mitochondrial functionality.