Hypertriglyceridemia secondary to obesity and diabetes

Hypertriglyceridemia is a common lipid abnormality in persons with visceral obesity, metabolic syndrome and type 2 diabetes. Hypertriglyceridemia typically occurs in conjunction with low HDL levels and atherogenic small dense LDL particles and is associated with increased cardiovascular risk. Insulin resistance is often an underlying feature and results in increased free fatty acid (FFA) delivery to the liver due to increased peripheral lipolysis. Increased hepatic VLDL production occurs due to increased substrate availability via FFAs, decreased apolipoprotein B100 degradation and increased lipogenesis. Postprandial hypertriglyceridemia also is a common feature of insulin resistance. Small dense LDL that coexist with decreased HDL particles in hypertriglyceridemic states are highly pro-atherogenic due to their enhanced endothelial permeability, proteoglycan binding abilities and susceptibility to oxidation. Hypertriglyceridemia also occurs in undertreated individuals with type 1 diabetes but intensive glucose control normalizes lipid abnormalities. However, development of visceral obesity in these patients unravels a similar metabolic profile as in patients with insulin resistance. Modest hypertriglyceridemia increases cardiovascular risk, while marked hypertriglyceridemia should be considered a risk for pancreatitis. Lifestyle modification is an important therapeutic strategy. Drug therapy is primarily focused on lowering LDL levels with statins, since efforts at triglyceride lowering and HDL raising with fibrates and/or niacin have not yet been shown to be beneficial in improving cardiovascular risk. Fibrates, however, are first-line agents when marked hypertriglyceridemia is present. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

► Low HDL and increased small dense LDL accompany hypertriglyceridemia of obesity.
► Increased FFA flux to the liver and increased apo B production are contributory.
► Management involves lifestyle changes with drug therapy to lower LDL cholesterol.