Antiatherogenic Effect of Pioglitazone in Type 2 Diabetic Patients Irrespective of the Responsiveness to Its Antidiabetic Effect

Antiatherogenic Effect of Pioglitazone in Type 2 Diabetic Patients Irrespective of the Responsiveness to Its Antidiabetic Effect Noriko Satoh , MD, PHD 1 , Yoshihiro Ogawa , MD, PHD 2 , Takeshi Usui , MD, PHD 1 , Tetsuya Tagami , MD, PHD 1 , Shigeo Kono , MD, PHD 1 , Hiroko Uesugi , MD, PHD 3 , Hiroyuki Sugiyama , MD, PHD 3 , Akira Sugawara , MD, PHD 1 , Kazunori Yamada , MD, PHD 1 , Akira Shimatsu , MD, PHD 1 , Hideshi Kuzuya , MD, PHD 1 and Kazuwa Nakao , MD, PHD 2 1 Diabetes Center and Clinical Research Institute of Kyoto National Hospital, Kyoto, Japan 2 Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan 3 Department of Internal Medicine, Saiseikai Noe Hospital, Osaka, Japan Address correspondence and reprint requests to Yoshihiro Ogawa, MD, PhD, Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. E-mail: ogawa.mmm{at}mri.tmd.ac.jp Abstract OBJECTIVE —Thiazolidinediones (TZDs), a class of insulin-sensitizing agents used clinically to treat type 2 diabetes, are also antiatherogenic. This study was designed to elucidate the relationship between the antiatherogenic and antidiabetic effects of pioglitazone, a TZD, in type 2 diabetic patients. RESEARCH DESIGN AND METHODS —A total of 136 Japanese type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (30 mg daily for 3 months) ( n = 70) and the untreated control group ( n = 66). The changes in glycolipid metabolism as well as plasma high-sensitivity C-reactive protein (CRP), leptin, adiponectin, and pulse wave velocity (PWV) were monitored to analyze the relationship between the antiatherogenic and antidiabetic effects of pioglitazone. RESULTS —The pioglitazone treatment significantly reduced hyperglycemia, hyperinsulinemia, and HbA 1c levels and increased plasma adiponectin concentrations relative to the control group ( P < 0.01). It also significantly decreased CRP and PWV ( P < 0.01). The antiatherogenic effect was observed in both the nonresponders showing 1% of reduction ( n = 40). ANCOVA revealed that treatment with pioglitazone was associated with a low CRP and PWV, independent of the changes in parameters related to glucose metabolism. CONCLUSIONS —This study represents the first demonstration of the antiatherogenic effect of