Lipid modification in type 2 diabetes: the role of LDL and HDL

Abstract

Patients with type 2 diabetes feature important modification of both low density lipoprotein (LDL) and high density lipoprotein particles which are likely to play an important role in the development of atherosclerosis. Although plasma LDL cholesterol level is usually normal in type 2 diabetic patients, LDLs show a significant increase in their plasma residence time which may promote cholesterol deposition in the arterial wall. Moreover, important qualitative abnormalities of LDLs, potentially atherogenic, are observed in type 2 diabetic patients: small dense, triglyceride-rich, LDL particles (known as subclass B), oxidized LDL and glycated LDL. All these qualitative modification of LDLs amplify the atherosclerotic process. Plasma high density lipoprotein (HDL) cholesterol is decreased in type 2 diabetes related to increased catabolism of HDL particles. One of the mechanism responsible for increased catabolism of HDLs is hypertriglyceridemia, promoting through cholesteryl ester transfer protein (CETP) the transfer of triglycerides (TG) to HDL leading to the formation of TG-rich HDLs which are very good substrates for hepatic lipase, enzyme in charge of HDLs catabolism. The reduction in plasma adiponectin level, observed in type 2 diabetes may be another mechanism involved in the diminution of HDL cholesterol. Furthermore, qualitative abnormalities of HDLs are described in type 2 diabetes: enrichment in triglycerides and glycation, which may impair HDL-mediated cholesterol efflux and reverse cholesterol transport. In addition to their role in reverse cholesterol transport, HDLs usually show antioxidative, anti-inflammatory, anti-thrombotic and endothelium-dependent vasorelaxant effects. It has been shown that HDLs from patients with type 2 diabetes have a significant reduction in their antioxidative and endothelium-dependent vasorelaxant properties.