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Diabetes Care 28:2975-2977, 2005
© 2005 by the American Diabetes Association, Inc.


Editorials
Supplement Article

Why Might Thiazolidinediones Increase Exercise Capacity in Patients With Type 2 Diabetes?

Nathan K. LeBrasseur, PHD1 and Neil B. Ruderman, MD, DPHIL2

1 Muscle and Aging Research Unit, Boston University School of Medicine, Boston, Massachusetts
2 Diabetes and Metabolism 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

The first 20% of the full text of this article appears below.

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 · kg–1 · min–1 or ~7.1%). These observations raise three fundamental questions: 1) Why is type 2 diabetes associated with a decrease in exercise capacity? 2) How might TZDs, such as RSG, counteract this? and 3) Is the effect of RSG on exercise capacity likely to be clinically relevant?

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., (4–6) 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) (~26 and 59%, respectively), smaller mitochondria, and higher intramyocellular triglyceride content than muscle of normal control subjects. Their data also suggested that subsarcolemmal mitochondria were especially affected. In addition to these findings, Mootha . . . [Full Text of this Article]


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Related Article:

Rosiglitazone Improves Exercise Capacity in Individuals With Type 2 Diabetes
Judith G. Regensteiner, Timothy A. Bauer, and Jane E.B. Reusch
Diabetes Care 2005 28: 2877-2883. [Abstract] [Full Text] [PDF]



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Copyright © 2005 by the American Diabetes Association.