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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2456.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Nateglinide Reduces Carotid Intima-Media Thickening in Type 2 Diabetic Patients Under Good Glycemic Control

Tomoya Mita; Hirotaka Watada; Tomoaki Shimizu; Yoshifumi Tamura; Fumihiko Sato; Takahiro Watanabe; Jong Bock Choi; Takahisa Hirose; Yasushi Tanaka; Ryuzo Kawamori

From the Department of Medicine, Metabolism, and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan.

Correspondence to A/Prof. Hirotaka Watada, MD, PhD, Department of Medicine, Metabolism, and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail hwatada{at}med.juntendo.ac.jp

Objective— Postprandial hyperglycemia observed in type 2 diabetes mellitus is a risk factor for atherosclerosis. The aim of this study was to investigate the effect of strict glycemic control by nateglinide on common carotid far wall intima-media thickness in type 2 diabetic patients who were already under good glycemic control.

Methods and Results— We performed an open labeled randomized prospective trial on 78 drug-naive type 2 diabetic patients whose HbA₁c was less than 6.5%. Thirty-eight patients were randomly assigned to receive nateglinide (270 mg/dL) and 40 to control group (no treatment). After 12 months, a significant reduction in HbA₁c was observed in the nateglinide group, whereas a significant increase of HbA₁c was observed in the untreated group. The carotid intima-media thickness at the end of 1-year follow-up was significantly reduced in the nateglinide group compared with the untreated group (–0.017±0.054 mm/year versus 0.024±0.066 mm/year, P=0.0064). Whereas nateglinide treatment also reduced triglyceride, highly-sensitive C-reactive protein, and E-selectin, multiple regression analysis identified HbA₁c as the only significant independent determinant of the change in carotid intima-media thickness.

Conclusion— In type 2 diabetic patients with good glycemic control, further strict glycemic control by nateglinide results in regression of carotid intima-media thickness.

To investigate the effect of nateglinide on atherosclerosis, we performed an open labeled randomized prospective trial on drug-naive type 2 diabetic patients whose HbA₁c was less than 6.5%. The carotid intima-media thickness at the end of 1-year follow-up period was significantly decreased in the nateglinide group compared with the untreated group. In type 2 diabetic patients under good glycemic control, further strict glycemic control by nateglinide results in regression of carotid intima-media thickness.

Key Words: intima-media thickness • atherosclerosis • strict glycemic control • postprandial hyperglycemia • type 2 diabetes

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