Metabolic flexibility and oxidative capacity independently associate with insulin sensitivity in individuals with...

Both inherited and acquired insulin resistance have been associated with abnormal muscle mitochondrial function. At whole-body level, maximal oxygen uptake ([Formula: see text]) and/or metabolic flexibility (as given by ΔRQ) reflect certain features of mitochondrial function. This study tests the hypotheses (1) that [Formula: see text] and ΔRQ correlate tightly with each other and with insulin sensitivity and (2) that glycaemia, lipidaemia or subclinical inflammation would explain such relationships.

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.

Both [Formula: see text] (r = 0.39, p < 0.0001) and ΔRQ (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. [Formula: see text] further correlated negatively with circulating high-sensitivity C-reactive protein concentration. However, [Formula: see text] did not relate to ΔRQ, even after adjusting for whole-body insulin sensitivity.

Oxidative capacity and metabolic flexibility are independent determinants of insulin sensitivity but are influenced by circulating NEFA in recent-onset type 2 diabetes. ClinicalTrial.gov registration no: NCT01055093.