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A Randomized Comparison of Pioglitazone to Inhibit Restenosis After Coronary Stenting in Patients With Type 2 Diabetes

¹ Third Department of Internal Medicine, School of Medicine, Showa University, Tokyo, Japan
² First Department of Internal Medicine, School of Medicine, Showa University, Tokyo, Japan

Address correspondence and reprint requests to Kazuaki Nishio, MD, PhD, Heights Matsugaoka 202, 4105 Katsuyama, Fijikawaguchiko-machi, Minamitsuru-gun, Yamanashi, 401-0310 Japan. E-mail: kazukun{at}jg7.so-net.ne.jp

OBJECTIVE—Recent studies have demonstrated that the treatment with thiazolidinediones reduces in-stent restenosis. The aim of this study was to elucidate the mechanism of the efficacy of pioglitazone for preventing in-stent restenosis in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—We conducted a prospective, randomized trial involving 54 type 2 diabetic patients referred for coronary stenting who were randomly assigned to either the control or the pioglitazone group. Quantitative coronary angiography was performed at study entry and at 6 months follow-up. Endothelial nitric oxide synthase (eNOS), tumor necrosis factor , interleukin-6, leptin, and adiponectin were measured at study entry and at 6 months follow-up.

RESULTS—A total of 28 patients were randomly assigned to the control group, and 26 patients were assigned to the pioglitazone group. There were no significant differences in glycemic control levels or in lipid levels in the two groups at baseline or at follow-up. Insulin, homeostasis model assessment of insulin resistance, eNOS, and leptin at follow-up were significantly reduced in the pioglitazone group compared with the control group. The late luminal loss and in-stent restenosis were significantly less in the pioglitazone group than in the control group. Leptin independently correlated with late luminal loss at multiple regression analysis.

CONCLUSIONS—The treatment with pioglitazone in type 2 diabetic patients significantly reduced leptin. This decreased leptin improved insulin resistance and endothelial function with the reduction of insulin. The improved endothelial function affected the reduction of in-stent restenosis.

Abbreviations: AMI, acute myocardial infarction • eNOS, endothelial nitric oxide synthase • FPG, fasting plasma glucose • HOMA-IR, homeostasis model assessment of insulin resistance • TZD, thiazolidinedione

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