PPAR‐alpha: therapeutic role in diabetes‐related cardiovascular disease
- 18 August 2008
- journal article
- review article
- Published by Wiley in Diabetes, Obesity and Metabolism
- Vol. 10 (9) , 691-698
Abstract
Among individuals with diabetes mellitus, cardiovascular disease remains the leading cause of death, despite the many treatment modalities that have been developed over time. The PPAR family, including PPAR‐alpha, play important roles in glucose and lipid metabolism and atherosclerosis and thus are potential therapeutic targets. Fibrates act upon PPAR‐alpha and appear to target the typical dyslipidaemia of diabetes. Several large prospective clinical trials have shown both primary prevention and secondary prevention benefit with fibrates, although they only had small subgroups of patients with diabetes. The first large outcome study to exclusively study those with diabetes was the FIELD study, which showed no reduction in the primary cardiovascular end‐point and only some benefit in the secondary end‐point. There are many potential explanations for these results; however, it would appear that at present, there is no role for fibrates as monotherapy for the reduction of cardiovascular risk among those with diabetes. However, their potential role in combination with statin therapy remains to be further elucidated with ongoing studies.Keywords
This publication has 42 references indexed in Scilit:
- Fenofibrate therapy and cardiovascular protection in diabetes: recommendations after FIELDCurrent Opinion in Lipidology, 2006
- PPARα agonist fenofibrate improves diabetic nephropathy in db/db miceKidney International, 2006
- Activation of Peroxisome Proliferator-activated Receptor-?? Decreases Endothelin-1-induced p38 Mitogen-activated Protein Kinase Activation in CardiomyocytesJournal of Cardiovascular Pharmacology, 2004
- Peroxisome Proliferator-Activated Receptor α Agonists Increase Nitric Oxide Synthase Expression in Vascular Endothelial CellsArteriosclerosis, Thrombosis, and Vascular Biology, 2004
- Serum homocysteine concentrations, gemfibrozil treatment, and progression of coronary atherosclerosisAtherosclerosis, 2004
- MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trialThe Lancet, 2002
- Peroxisome proliferator-activated receptor-α activation and high-density lipoprotein metabolismThe American Journal of Cardiology, 2001
- Activation of Proliferator-activated Receptors α and γ Induces Apoptosis of Human Monocyte-derived MacrophagesJournal of Biological Chemistry, 1998
- Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor.Journal of Clinical Investigation, 1995
- Helsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in Middle-Aged Men with DyslipidemiaNew England Journal of Medicine, 1987