Hypertriglyceridemic hyperapoB: The unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus

Abnormalities in insulin and glucose metabolism do not seem to entirely account for the high frequency of cardiovascular disease in patients with type 2 diabetes mellitus. An important additional factor may be hypertriglyceridemic hyperapoB, an atherogenic dysilpoproteinemia that is common in these patients. The major features of hypertriglyceridemic hyperapoB are hypertriglyceridemia; low levels of high-density lipoprotein cholesterol; and increased numbers of small, dense low-density lipoprotein (LDL) particles. This article reviews the pathophysiology of this disorder, focusing on the changes in lipoprotein particle number and composition rather than lipoprotein lipid levels. The in vitro and in vivo evidence that small, dense LDL are more atherogenic than normal larger, buoyant LDL is summarized, and the particularly high-risk state conferred by increased numbers of small, dense LDL is delineated. This review demonstrates how abnormalities in the plasma lipoproteins may relate to the effectiveness with which adipose tissue traps and retains fatty acid. The effects of increased fatty acid flux on the hepatic metabolism of lipids and apoB secretion are detailed, and the mechanisms by which fibrates and statins may improve these are described. An understanding of these principles should provide the physician with a more physiologic basis on which to choose appropriate therapy.