Metabolic flexibility and oxidative capacity independently associate with insulin sensitivity in individuals with newly diagnosed type 2 diabetes

Aims/hypothesis Both inherited and acquired insulin resistance have been associated with abnormal muscle mitochondrial function. At whole-body level, maximal oxygen uptake (VO2max) and/or metabolic flexibility (as given by Delta RQ) reflect certain features of mitochondrial function. This study tests the hypotheses (1) that and Delta RQ correlate tightly with each other and with insulin sensitivity and (2) that glycaemia, lipidaemia or subclinical inflammation would explain such relationships. Methods Near-normoglycaemic individuals with type 2 diabetes mellitus (n = 136) with a short known disease duration (<12 months) underwent cycling spiroergometry, indirect calorimetry and hyperinsulinaemic-euglycaemic clamp tests. Results Both (r = 0.39, p < 0.0001) and Delta RQ (r = 0.32, p < 0.0001) correlated positively with whole-body insulin sensitivity, even after adjusting for anthropometric variables, glycaemia and glucose-lowering medication, but not after adjusting for NEFA. further correlated negatively with circulating high-sensitivity C-reactive protein concentration. However, did not relate to Delta RQ, even after adjusting for whole-body insulin sensitivity. Conclusions/interpretation Oxidative capacity and metabolic flexibility are independent determinants of insulin sensitivity but are influenced by circulating NEFA in recent-onset type 2 diabetes.