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

Abnormalities in insulin and glucose metabolism do not seem to entirely acc ount for the high frequency of cardiovascular disease in patients with type 2 diabetes mellitus. An important additional factor may be hypertriglyceri demic hyperapoB, an atherogenic dysilpoproteinemia that is common in these patients. The major features of hypertriglyceridemic hyperapoB are hypertri glyceridemia; low levels of high-density lipoprotein cholesterol; and incre ased numbers of small, dense low-density lipoprotein (LDL) particles. This article reviews the pathophysiology of this disorder, focusing on the chang es in lipoprotein particle number and composition rather than lipoprotein l ipid levels. The in vitro and in vivo evidence that small, dense LDL are mo re atherogenic than normal larger, buoyant LDL is summarized, and the parti cularly high-risk state conferred by increased numbers of small, dense LDL is delineated. This review demonstrates how abnormalities in the plasma lip oproteins may relate to the effectiveness with which adipose tissue traps a nd retains fatty acid. The effects of increased fatty acid flux on the hepa tic metabolism of lipids and apoB secretion are detailed, and the mechanism s by which fibrates and statins may improve these are described. An underst anding of these principles should provide the physician with a more physiol ogic basis on which to choose appropriate therapy.