Rosiglitazone Improves Exercise Capacity in Individuals With Type 2 Diabetes

OBJECTIVE:--Although exercise is recommended as a cornerstone of treatment for type 2 diabetes, it is often poorly adopted by patients. We have noted that even in the absence of apparent cardiovascular disease, persons with type 2 diabetes have an impaired ability to carry out maximal exercise, and the impairment is correlated with insulin resistance and endothelial dysfunction. We hypothesized that administration of a thiazolidinedione (TZD) agent would improve exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS--Twenty participants with uncomplicated type 2 diabetes were randomly assigned in a double-blind study to receive either 4 mg/day of rosiglitazone or matching placebo after baseline measurements to assess endothelial function (brachial artery diameter by brachial ultrasound), maximal oxygen consumption ({Vdot}O[subscript 2max]), oxygen uptake ({Vdot}O₂) kinetics, and insulin sensitivity by hyperinsulinemic-euglycemic clamp. Measurements were reassessed after 4 months of treatment. RESULTS:--Participant groups did not differ at baseline in any measure. Rosiglitazone-treated participants (n = 10) had significantly improved {Vdot}O[subscript 2max] (19.8 ± 5.3 ml · kg⁻¹ · min⁻¹ before rosiglitazone vs. 21.2 ± 5.1 ml · kg⁻¹ · min⁻¹ after rosiglitazone, P < 0.01), insulin sensitivity, and endothelial function. A change in {Vdot}O[subscript 2max] correlated with improved insulin sensitivity measured by clamp (r = 0.68, P < 0.05) and with improved brachial artery diameter (r = 0.70, P < 0.05). Placebo-treated participants (n = 10) showed no changes in {Vdot}O[subscript 2max] (19.4 ± 5.2 ml · kg⁻¹ · min⁻¹ before rosiglitazone vs. 18.1 ± 5.3 ml · kg⁻¹ · min⁻¹ after rosiglitazone, NS) or brachial artery diameter. CONCLUSIONS:--This is the first known report showing that a TZD improved exercise function in type 2 diabetes. Whether this is due to the observed improvements in insulin sensitivity and/or endothelial function or to another action of the TZD class requires further exploration.