Effect of Peroxisome Proliferator–Activated Receptor γ Agonist Treatment on Subclinical Atherosclerosis in Patients With Insulin-Requiring Type 2 Diabetes

  1. Howard N. Hodis, MD123,
  2. Wendy J. Mack, PHD23,
  3. Ling Zheng, PHD24,
  4. Yanjie Li, MD3,
  5. Mina Torres, MS23,
  6. Diego Sevilla, PA1,
  7. Yolanda Stewart, BS14,
  8. Barbara Hollen, MPH1,
  9. Karla Garcia, BA14,
  10. Petar Alaupovic, PHD5 and
  11. Thomas A. Buchanan, MD14
  1. 1Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California
  2. 2Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California
  3. 3Atherosclerosis Research Unit, University of Southern California Keck School of Medicine, Los Angeles, California
  4. 4General Clinical Research Center, University of Southern California Keck School of Medicine, Los Angeles, California
  5. 5Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma
  1. Address correspondence and reprint requests to Howard N. Hodis, MD, Atherosclerosis Research Unit, University of Southern California Keck School of Medicine, 2250 Alcazar St., CSC 132, Los Angeles, CA 90033. E-mail: athero{at}usc.edu

Abstract

OBJECTIVE—To determine the effect of thiazolidinedione treatment on subclinical atherosclerosis progression in insulin-requiring patients with clinical characteristics suggesting type 2 diabetes.

RESEARCH DESIGN AND METHODS—Eligible participants (n = 299) were randomized within strata of baseline common carotid artery (CCA) intima-media thickness (IMT) (<0.8 mm, ≥0.8 mm) to 400 mg troglitazone daily or placebo for 2 years. A general linear mixed-effects model was used to compare the rate of change in CCA-IMT between treatment groups.

RESULTS—Overall, average rates of CCA-IMT change were not significantly different between troglitazone- and placebo-treated subjects (0.0030 ± 0.021 vs. 0.0066 ± 0.021 mm/year; P = 0.17). In the stratum of subjects with CCA-IMT ≥0.8 mm, troglitazone significantly reduced the progression of CCA-IMT relative to placebo (0.0013 ± 0.022 vs. 0.0084 ± 0.023 mm/year; P = 0.03). Fasting glucose, insulin, and HbA1c were significantly lower in troglitazone- versus placebo-treated subjects (P < 0.01). Whereas blood pressure significantly differed between treatment groups in the ≥0.8-mm stratum, there was no difference between treatment groups in the <0.8-mm stratum.

CONCLUSIONS—Insulin sensitization and reduction in blood pressure may be contributory mechanisms by which troglitazone reduced subclinical atherosclerosis progression in this cohort of well-controlled insulin-dependent patients with clinical characteristics suggesting type 2 diabetes.

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted April 9, 2006.
    • Received December 14, 2005.
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