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- November 20, 2008 |
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"TZDs and Atherosclerosis: Can They Make a Difference?"Dr. Lawrence A. Leiter (biography)
English - 2005-10-25 - 36 minutes
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Summary :
Vascular disease is a leading cause of death in diabetes, and cardiovascular risk is increased even before the diagnosis of diabetes, as seen in the Nurses' Health Study (1). How well is glycemia being controlled in type 2 diabetic patients in Canada? The cross-sectional DICE (Diabetes in Canada Evaluation) study showed that half of the patients are not at target. Although physicians seem to be aware of the glycemic target there is a lack of aggressive treatment of uncontrolled patients.
Insulin resistance has been associated with increased cardiovascular risk (2,3). The insulin-sensitizing glitazone drugs (TZDs) have a number of potentially anti-atherosclerotic effects, and it is being investigated in several prospective trials whether they can reduce cardiovascular risk. There is already evidence from different studies to suggest that this is the case (4-7).
The PROactive (PROspective PioglitAzone Clinical Trial In MacroVascular Events) Study was recently presented at the 2005 EASD meeting and published in The Lancet. This was a prospective, randomised, controlled macrovascular outcome study with 2.5 years follow-up, in type 2 diabetic patients at increased cardiovascular risk, comparing pioglitazone with placebo in addition to existing therapy. Dr. Leiter reviews the study design, outcomes and safety data obtained from the study (8).
Finally, numerous clinical trials are ongoing with glitazones that are designed to ascertain their effects on cardiovascular risk in different patient populations. Dr. Leiter gives an overview of these studies: ACCORD, VADT, PERISCOPE, PPAR, CHICAGO, VICTORY, RECORD and BARI-2D.
Copyright © 2005 E-MedHosting.com Inc.
Learning objectives :
Key learning points:
1. TZDs can decrease multiple traditional and non-traditional CV risk factors.
2. There are now a number of trials using surrogate endpoints suggesting decreased CV risk in TZD-treated patients.
3. The results of the PROACTIVE study, although not definitive, are consistent with the anti-atherosclerotic effects of TZDs.
4. Ongoing clinical trials will hopefully definitively reveal if TZDs reduce CV risk.
Bibliographic references :
1. Haffner SJ, Cassells H. Hyperglycemia as a cardiovascular risk factor. The American Journal of Medicine. 115(8), 6-11.
2. Hanley AJ, Williams K, Stern MP, Haffner SM. Homeostasis Model Assessment of Insulin Resistance in Relation to the Incidence of Cardiovascular Disease. Diabetes Care. 2002 Vol. 25, 1177-1184.
3. Enzo Bonora, Gianni Formentini, Francesco Calcaterra, Simonetta Lombardi, Franco Marini, Luciano Zenari, Francesca Saggiani, Maurizio Poli, Sandro Perbellini, Andrea Raffaelli, Vittorio Cacciatori, Lorenza Santi, Giovanni Targher, Riccardo Bonadonna, and Michele Muggeo. HOMA-Estimated Insulin Resistance Is an Independent Predictor of Cardiovascular Disease in Type 2 Diabetic Subjects - Prospective data from the Verona Diabetes Complications Study. Diabetes Care. 2002 Vol. 25, 1135-1141.
4. Jagdip S. Sidhu; Zoltan Kaposzta; Hugh S. Markus; Juan Carlos Kaski. Effect of Rosiglitazone on Common Carotid Intima-Media Thickness Progression in Coronary Artery Disease Patients Without Diabetes Mellitus. Arteriosclerosis, Thrombosis, and Vascular Biology. May 2004; 24 930 – 934.
5. Hiroyuki Koshiyama, Dai Shimono, Naomitsu Kuwamura, Jun Minamikawa, and Yoshio Nakamura. RAPID COMMUNICATION: Inhibitory Effect of Pioglitazone on Carotid Arterial Wall Thickness in Type 2 Diabetes. The Journal of Clinical Endocrinology and Metabolism. July 2001; 86, 3452-6.
6. Choi SH et al. Diabetes. 2003;52 (suppl 1):A18. Oral presentation 82-0R.
7. Masoudi F.A. et al. Diabetes 2004; 53(Suppl.2);A29.
8. The official PROactive results website
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