Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction

Several lines of evidence support a potential role of skeletal muscle mitochondrial dysfunction in the pathogenesis of insulin resistance and/or type 2 diabetes. However, it remains to be established whether mitochondrial dysfunction represents either cause or consequence of the disease. We examined in vivo skeletal muscle mitochondrial function in early and advanced stages of type 2 diabetes, with the aim to gain insight in the proposed role of mitochondrial dysfunction in the aetiology of insulin resistance and/or type 2 diabetes.

Ten long-standing, insulin-treated type 2 diabetes patients, 11 subjects with impaired fasting glucose, impaired glucose tolerance and/or recently diagnosed type 2 diabetes, and 12 healthy, normoglycaemic controls, matched for age and body composition and with low habitual physical activity levels were studied. In vivo mitochondrial function of the vastus lateralis muscle was evaluated from post-exercise phosphocreatine (PCr) recovery kinetics using (31)P magnetic resonance spectroscopy (MRS). Intramyocellular lipid (IMCL) content was assessed in the same muscle using single-voxel (1)H MRS.

IMCL content tended to be higher in the type 2 diabetes patients when compared with normoglycaemic controls (P=0.06). The(31)P MRS parameters for mitochondrial function, i.e. PCr and ADP recovery time constants and maximum aerobic capacity, did not differ between groups.

The finding that in vivo skeletal muscle oxidative capacity does not differ between long-standing, insulin-treated type 2 diabetes patients, subjects with early stage type 2 diabetes and sedentary, normoglycaemic controls suggests that mitochondrial dysfunction does not necessarily represent either cause or consequence of insulin resistance and/or type 2 diabetes.