Mitochondrial cristae density is increased following high-intensity interval training in men with type 2 diabetes

AIMS/HYPOTHESIS: Mitochondrial cristae architecture is a key determinant of oxidative capacity in skeletal muscle. While mitochondrial dysfunction is common in type 2 diabetes, it remains unclear whether cristae density is reduced and whether it can be improved by exercise training. We therefore investigated the mitochondrial cristae density in skeletal muscle of individuals with type 2 diabetes compared with glucose-tolerant individuals with obesity and lean individuals, and examined the effect of high-intensity interval training (HIIT). METHODS: In a non-randomised intervention study, the effect of an 8 week supervised HIIT intervention combining rowing and cycling was examined in male participants (aged 40-65 years) with type 2 diabetes (n=15), glucose-tolerant individuals with obesity (n=15), and lean individuals (n=18). Muscle biopsies from the vastus lateralis muscle were analysed using transmission electron microscopy to quantify mitochondrial cristae density (cristae surface area per mitochondrial volume) and to derive cristae surface area per muscle volume, integrating mitochondrial abundance and ultrastructure. To ensure high stereological precision, a minimum of 49 mitochondrial profiles per sample were analysed. RESULTS: No differences in mitochondrial cristae density were observed between groups at baseline. HIIT induced a ~7% increase in cristae density across all groups, with the most pronounced adaptations in type 2 fibres and in the intermyofibrillar compartment. At baseline, participants with type 2 diabetes exhibited lower cristae surface area per muscle volume compared with lean individuals. Notably, HIIT increased cristae surface area per muscle volume by ~55%, exceeding the magnitude of previously reported increases in mitochondrial volume density. CONCLUSIONS/INTERPRETATION: Skeletal muscle mitochondrial cristae density is not different between individuals with type 2 diabetes and glucose-tolerant individuals with obesity and lean individuals, and the capacity for cristae remodelling in response to exercise is not affected by type 2 diabetes. These findings highlight the plasticity of mitochondrial architecture and support HIIT as a potent stimulus for improving muscle oxidative and metabolic health in type 2 diabetes.