Purpose: We examined the effect of a 1-year treatment with the insulin sensitizer PPAR-gamma agonist rosiglitazone in addition to standard care on exercise capacity and body fat composition/distribution in men with T2DM and coronary artery disease (CAD).
Methods: A total of 104 men (age: 64±7 years; body mass index: 30.0±4.4 kg/m2) with T2DM (mean duration: 7.5 years) and CAD were randomized to receive rosiglitazone or placebo for 1 year. Exercise capacity (exercise duration) was assessed with a maximal treadmill test and body composition/distribution were assessed by dual-energy X-ray absorptiometry (DEXA)/computed tomography prior the intervention and at 1-year follow-up.
Results: At 1 year, patients with T2DM under PPAR-gamma agonist treatment showed a reduction in exercise capacity compared to the control group (exercise duration change, -31 ± 8 vs. 7 ± 11 s, p=0.009). Significant increases in body fat mass (3.1 ± 0.4 kg, 12%), abdominal and mid-thigh subcutaneous adipose tissue (AT) levels, and mid-thigh skeletal muscle fat were found (all p <0.01), whereas no effect on visceral AT levels was observed following treatment (p >0.05). PPAR-gamma agonist treated patients showed significant improvements in insulin sensitivity (HOMA-IR) and fasting blood glucose despite weight gain and body fat mass expansion (all p <0.05). Subcutaneous fat mass gained under PPAR-gamma agonist was the strongest predictor of the worsening in exercise capacity in a multivariate model (p ?0.0001); no association was found with skeletal muscle fat infiltration nor visceral AT levels.
Conclusions: Treatment with the insulin sensitizer PPAR-gamma agonist rosiglitazone in patients with T2DM and stable CAD is associated with a worsening in exercise capacity, which seems to be mainly attributable to subcutaneous fat mass expansion.