The effects of fibrates on lipid metabolism and inflammation in type 2 diabetes

Abstract

Type 2 diabetes is associated with a cluster of cardiovascular risk factors that together promote macrovascular and microvascular disease. An atherogenic dyslipidaemia, characterised by an increase in serum triglyceride-rich lipoproteins, a decrease in plasma levels of high-density lipoprotein cholesterol (HDL-C) and increased prevalence of small, dense low-density lipoprotein (LDL) particles (although LDL-C levels are normal or only modestly elevated), as well as chronic inflammation, play key roles in the pathogenesis of diabetes-related complications. As peroxisome proliferator-activated receptor a agonists, the fibrates exert an integrated action to favour normalisation of lipid metabolism, cholesterol homeostasis and reverse cholesterol transport, inflammation and haemostasis, suggesting potential efficacy in preventing vascular complications of diabetes. By synergistic therapeutic targeting of abnormalities in lipid metabolism and inflammation, fenofi-brate can promote anti-atherogenic effects at the arterial wall, as demonstrated in the Diabetes Atherosclerosis Intervention Study (DAIS), and reduction of total cardiovascular events, as shown in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.