Mitochondrial dysfunction in calf muscles of patients with combined peripheral arterial disease and diabetes type 2.

BACKGROUND: This study elucidates the effects on muscle mitochondrial function in patients suffering from combined peripheral arterial disease (PAD) and type 2 diabetes (T2D) and the relation to patient symptoms and treatment. METHODS: Near infrared spectroscopy (NIRS) calf muscle exercise tests were conducted on 40 subjects, 15 (PAD), 15 (PAD+T2D) and 10 healthy age matched controls (CTRL) recruited from the vascular outpatient clinic at Gentofte County Hospital, Denmark. Calf muscle biopsies (~80 mg, gastrocnemius and anterior tibial muscles) were sampled and mitochondrial function tested applying high resolution oxygraphy on isolated muscle fibers. RESULTS: The NIRS exercise tests showed evidence of mitochondrial dysfunction in the PAD+T2D group by a longer recovery of the deoxygenation resulting from exercise in spite of a higher exercise oxygenation level compared to the PAD group. This was confirmed by a ~30% reduction in oxygen consumption in the muscle biopsy tests for the PAD+T2D compared to the PAD group (P<0.05). We claim that this mitochondrial dysfunction partly explains the ~30% reduction in tread mill walking distance for the PAD+T2D group observed in this study. CONCLUSIONS: These findings support the use of early surgical revascularization in the PAD+T2D group, in order to obtain better walking performance and probably reduced risk of permanent mitochondrial damage.