© 2005 by the American Diabetes Association, Inc.
Why Might Thiazolidinediones Increase Exercise Capacity in Patients With Type 2 Diabetes?
1 Muscle and Aging Research Unit, Boston University School of Medicine, Boston, Massachusetts Address correspondence to Neil B. Ruderman, MD, DPhil, Diabetes and Metabolism Research Unit, Boston University School of Medicine, 650 Albany St., X-820, Boston, MA 02118. E-mail: nrude@bumc.bu.edu
Individuals with type 2 diabetes are insulin resistant and as a group have a lower exercise capacity (VO2max) than age- and weight-matched people without diabetes (1,2). In this issue, Regensteiner et al. (3) report that rosiglitazone (RSG), a thiazolidinedione (TZD) commonly used to treat insulin resistance, also improves exercise capacity in patients with type 2 diabetes. Following 4 months of treatment with 4 mg/day RSG, the authors observed expected improvements in insulin sensitivity as determined by homeostasis model assessment and a hyperinsulinemic-euglycemic clamp in 10 middle-aged men and women with type 2 diabetes. A novel finding was that RSG caused a modest but significant increase in VO2max (1.4 ml · kg1 · min1 or
Recent studies suggest several explanations for the decrease in VO2max in patients with type 2 diabetes. One of these is the presence of mitochondrial dysfunction. As reported by Kelley et al. and Ritov et al., (46) skeletal muscle of sedentary middle-aged individuals with established type 2 diabetes (HbA1c 8.0 ± 0.2%) exhibits reduced mitochondrial oxidative enzyme (succinate dehydrogenase) activity and electron transport chain capacity (rotenone-sensitive NADH:O2 oxido-reductase activity) (
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