Published online before print May 3, 2004, doi: 10.1161/01.CIR.0000126824.12785.B6
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;109:2197-2202.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Peroxisome Proliferator–Activated Receptor Ligand Bezafibrate for Prevention of Type 2 Diabetes Mellitus in Patients With Coronary Artery Disease
From the Cardiac Rehabilitation Institute (A.T., M.M., E.Z.F., E.S., Y.A.) and Bezafibrate Infarction Prevention Study Coordinating Center (I.G., J.L., V.B., L.M., S.B.), Neufeld Cardiac Research Institute, Chaim Sheba Medical Center, Tel-Hashomer, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Correspondence to Alexander Tenenbaum, MD, PhD, Cardiac Rehabilitation Institute, Chaim Sheba Medical Center, Tel-Hashomer, 52621 Israel. E-mail altenen{at}post.tau.ac.il or altenen{at}yahoo.com
Received November 14, 2002; de novo received November 5, 2003; revision received February 3, 2004; accepted February 6, 2004.
Background— Recent studies have shown that type 2 diabetes is preventable by both lifestyle interventions and medications that influence primary glucose metabolism. Whether pharmacological interventions that influence primary lipid metabolism can also delay development of type 2 diabetes is unknown. The goal of this study was to evaluate the effect of the peroxisome proliferator–activated receptor ligand bezafibrate on the progression of impaired fasting glucose phase to type 2 diabetes in patients with coronary artery disease over a 6.2-year follow-up period.
Methods and Results— The study sample comprised 303 nondiabetic patients 42 to 74 years of age with a fasting blood glucose level of 110 to 125 mg/dL (6.1 to 6.9 mmol/L). The patients received either 400 mg bezafibrate retard (156 patients) or placebo (147 patients) once a day. No patients were using statins, and use of ACE inhibitors, which also reduce diabetes incidence, was relatively low. During follow-up, development of new-onset diabetes was recorded in 146 patients: in 80 (54.4%) from the placebo group and 66 (42.3%) from the bezafibrate group (P=0.04). The mean time until onset of new diabetes was significantly delayed in patients on bezafibrate compared with patients on placebo: 4.6±2.3 versus 3.8±2.6 years (P=0.004). Multivariate analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes development (hazard ratio, 0.70; 95% CI, 0.49 to 0.99). Other significant variables associated with future overt type 2 diabetes in patients with impaired fasting glucose were total cholesterol level (hazard ratio, 1.22; 95% CI 1.0 to 1.51) and body mass index (hazard ratio, 1.10; 95% CI, 1.05 to 1.16).
Conclusions— Bezafibrate reduces the incidence and delays the onset of type 2 diabetes in patients with impaired fasting glucose. Whether the combination of bezafibrate with other recommended drugs for secondary prevention (statins and ACE inhibitors) would be as efficacious as suggested by our results remains to be determined.
Key Words: bezafibrate • coronary disease • diabetes mellitus • glucose • prevention
This article has been cited by other articles:
 |
|
 |
|
  J. Petremand, N. Bulat, A.-C. Butty, C. Poussin, S. Rutti, K. Au, S. Ghosh, V. Mooser, B. Thorens, J.-Y. Yang, et al. Involvement of 4E-BP1 in the Protection Induced by HDLs on Pancreatic {beta}-Cells Mol. Endocrinol., October 1, 2009; 23(10): 1572 - 1586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G. Drew, S. J. Duffy, M. F. Formosa, A. K. Natoli, D. C. Henstridge, S. A. Penfold, W. G. Thomas, N. Mukhamedova, B. de Courten, J. M. Forbes, et al. High-Density Lipoprotein Modulates Glucose Metabolism in Patients With Type 2 Diabetes Mellitus Circulation, April 21, 2009; 119(15): 2103 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Flory, S. Ellenberg, P. O. Szapary, B. L. Strom, and S. Hennessy Antidiabetic Action of Bezafibrate in a Large Observational Database Diabetes Care, April 1, 2009; 32(4): 547 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nakano, Y. Inada, H. Masuzaki, T. Tanaka, S. Yasue, T. Ishii, N. Arai, K. Ebihara, K. Hosoda, K. Maruyama, et al. Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1213 - E1222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bergeron, J. Yao, J. W. Woods, E. I. Zycband, C. Liu, Z. Li, A. Adams, J. P. Berger, B. B. Zhang, D. E. Moller, et al. Peroxisome Proliferator-Activated Receptor (PPAR)-{alpha} Agonism Prevents the Onset of Type 2 Diabetes in Zucker Diabetic Fatty Rats: A Comparison with PPAR{gamma} Agonism Endocrinology, September 1, 2006; 147(9): 4252 - 4262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lalloyer, B. Vandewalle, F. Percevault, G. Torpier, J. Kerr-Conte, M. Oosterveer, R. Paumelle, J.-C. Fruchart, F. Kuipers, F. Pattou, et al. Peroxisome Proliferator-Activated Receptor {alpha} Improves Pancreatic Adaptation to Insulin Resistance in Obese Mice and Reduces Lipotoxicity in Human Islets Diabetes, June 1, 2006; 55(6): 1605 - 1613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Okopien, R. Krysiak, and Z. S. Herman Effects of Short-Term Fenofibrate Treatment on Circulating Markers of Inflammation and Hemostasis in Patients with Impaired Glucose Tolerance J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1770 - 1778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tenenbaum, E. Z. Fisman, V. Boyko, M. Benderly, D. Tanne, M. Haim, Z. Matas, M. Motro, and S. Behar Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate. Arch Intern Med, April 10, 2006; 166(7): 737 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tenenbaum, M. Motro, E. Z. Fisman, Y. Adler, J. Shemesh, D. Tanne, J. Leor, V. Boyko, E. Schwammenthal, and S. Behar Effect of bezafibrate on incidence of type 2 diabetes mellitus in obese patients Eur. Heart J., October 1, 2005; 26(19): 2032 - 2038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden Second World Congress on the Insulin Resistance Syndrome: Hypertension, cardiovascular disease, and treatment approaches Diabetes Care, August 1, 2005; 28(8): 2073 - 2080. [Full Text] [PDF]
|
|
|
|
|
|
A. Tenenbaum, M. Motro, E. Z. Fisman, D. Tanne, V. Boyko, and S. Behar Bezafibrate for the Secondary Prevention of Myocardial Infarction in Patients With Metabolic Syndrome Arch Intern Med, May 23, 2005; 165(10): 1154 - 1160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Padwal, S. R. Majumdar, J. A. Johnson, J. Varney, and F. A. McAlister A Systematic Review of Drug Therapy to Delay or Prevent Type 2 Diabetes Diabetes Care, March 1, 2005; 28(3): 736 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Flavell, H. Ireland, J. W. Stephens, E. Hawe, J. Acharya, H. Mather, S. J. Hurel, and S. E. Humphries Peroxisome Proliferator-Activated Receptor {alpha} Gene Variation Influences Age of Onset and Progression of Type 2 Diabetes Diabetes, February 1, 2005; 54(2): 582 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Villareal and J. O. Holloszy Effect of DHEA on Abdominal Fat and Insulin Action in Elderly Women and Men: A Randomized Controlled Trial JAMA, November 10, 2004; 292(18): 2243 - 2248. [Abstract] [Full Text] [PDF]
|
|