Fitness Now Comes in a Pill!

Abstract & Commentary

By Ralph R. Hall, MD, FACP, FACSM, Emeritus Professor of Medicine University of Missouri-Kansas City School of Medicine. Dr. Hall is a consultant for Aventis.

Synopsis: Rosiglitazone improves exercise capacity in individuals with Type 2 Diabetes.

Source: Regensteiner JG, et al. Rosiglitazone improves exercise capacity in individuals with type 2 diabetes. Diabetes Care. 2005;28:2877-2883.

Regensteiner and colleagues observed that even in the absence of cardiovascular disease, persons with type 2 diabetes have an impaired ability to carry out maximal exercise, and that the impairment is correlated with insulin resistance and impaired endothelial function. They postulated that administration of a thiazolidinedione (TZD) would improve exercise capacity in type 2 diabetes.

Twenty patients with uncomplicated type 2 diabetes were randomly assigned in a double blind study to receive 4 mg/day of rosiglitazone or matching placebo after baseline measurements to assess endothelial function, maximal oxygen consumption (VO2max), oxygen uptake (VO2) kinetics, and insulin sensitivity by hyperinsulinemic-euglycemic clamp. Measurements were reassessed after 4 months of treatment.

Participant groups did not differ at baseline in any measure. Rosiglitazone-treated patients (n = 10) had significantly improved VO2max (19.8 ± 5.3 mL x kg-1 x min-1) before rosiglitazone vs 21.2 ± 5.1 mL x kg-1 x min-1 after rosiglitazone (P = 0.01). Insulin sensitivity and endothelial function also improved significantly. A change in VO2max correlated with improved insulin sensitivity and endothelial function. Placebo treated (n = 10) patients showed no improvement in VO2max, insulin sensitivity, or endothelial function after treatment with rosiglitazone.

This is the first report demonstrating that a TZD improved exercise function in type 2 diabetes. Whether this is due to observed improvements in insulin sensitivity and/or endothelial function or is due to another action of this class of anti-diabetic drugs is unknown.

Commentary

This is an interesting study but it should be viewed with some skepticism. It is small, the improvement in exercise capacity is small, and the it was of short duration. If the study were of longer duration, would the exercise capacity have improved more or would there have been a gradual return to baseline?

Despite these shortcomings this is a worthwhile study using a medication that has already demonstrated its value in the treatment of type 2 diabetes. This experiment was carried out by experienced investigators in a laboratory with demonstrated expertise in exercise testing and in the treatment of diabetics. They had reason to believe that the TZDs would increase exercise capacity based on the drug's mechanism of action.

The authors note that "the study was not designed to evaluate the mechanism by which rosiglitazone increased exercise capacity; the potential relationships between improved exercise capacity, endothelial function and insulin resistance, separately or together, require further investigation."

It is presumed that other TZDs will improve exercise capacity. If insulin resistance is an important factor then metformin should also improve exercise capacity.

LeBrasseur and Ruderman in an accompanying editorial1 discuss the potential mechanisms of action that lead to the improved exercise performance as the result of TZD treatment. Possible mechanisms include increased exercise capacity a result of improved mitochondrial function, improvement in muscle blood flow and oxygen extraction, a decrease in inflammatory cytokines and other mechanisms.

The other question for physicians treating type 2 diabetics is whether this small change in VO2max is clinically significant.

Reference

1. LeBrasseur NK, Ruderman NB. Diabetes Care. 2005;28:2975-2976.