Cardiorespiratory fitness and insulin sensitivity in overweight or obese subjects may be linked through intrahepatic lipid content


  • S. Haufe
  • S. Engeli
  • P. Budziarek
  • W. Utz
  • J. Schulz-Menger
  • M. Hermsdorf
  • S. Wiesner
  • C. Otto
  • V. Haas
  • A. de Greiff
  • F.C. Luft
  • M. Boschmann
  • J. Jordan


  • Diabetes


  • Diabetes 59 (7): 1640-1647


  • Objective: Low cardiorespiratory fitness predisposes to cardiovascular disease and type 2 diabetes mellitus in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL. Research Design and Methods: We included 138 overweight to obese, otherwise healthy subjects (age: 43.6 +/- 8.9 yrs., body mass index: 33.8 +/- 4 kg/m(2)). Body composition was estimated by bio-impedance analyses. Abdominal fat distribution, intramyocellular, and intrahepatic lipid content were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate individual's cardiorespiratory fitness. Insulin sensitivity was determined during an oral glucose tolerance test. Results: For all subjects, cardiorespiratory fitness was related to insulin sensitivity (r=0.32, p<0.05), IHL (r=-0.27, p<0.05), visceral (r=-0.25, p<0.05) and total fat mass (r=-0.32, p<0.05), but not to intramyocellular lipids (r=-0.08, ns). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat and fitness (r(2)=-0.43, p<0.01; r(2)=-0.34 and r(2)=0.29, p<0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r=0.16, ns), whereas it remained significant when adjusted for visceral- or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels. Conclusions: Our study suggests that the positive effect of increased cardiorespiratory fitness in overweight to obese subjects on insulin sensitivity may be mediated indirectly through IHL reduction.