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

Diabetologia. 2016 Oct;59(10):2203-7. doi: 10.1007/s00125-016-4038-9. Epub 2016 Jul 4.


Aims/hypothesis: 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.

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 [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.

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. registration no: NCT01055093.

Keywords: Energy metabolism; Inflammation; Insulin sensitivity; Mitochondria; Muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / metabolism*
  • C-Reactive Protein / metabolism
  • Calorimetry, Indirect
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glucose Clamp Technique
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Obesity / blood
  • Obesity / metabolism
  • Overweight / blood
  • Overweight / metabolism
  • Oxidation-Reduction
  • Oxygen Consumption / physiology
  • Young Adult


  • Blood Glucose
  • Insulin
  • C-Reactive Protein

Associated data