Pathophysiology of diabetic dyslipidemia:implications for atherogenesis and treatment

Many patients with Type 2 diabetes mellitus are characterized by a typical dyslipidemia. This dyslipidemia includes hypertriglyceridemia, low HDL-C and mildly elevated LDL-C with a predominance of small dense LDL particles. The mechanisms leading to hypertriglyceridemia directlyrelate to insulin resistance and hyperglycemia. Both factors result in overproduction of triglyceride-rich lipoproteins from the liver, decreased clearance of triglyceride-rich lipoproteins and, in some cases, an altered postprandial lipoprotein metabolism. The origin of low HDL-C and the predominance of small dense LDL is closely linked to hypertriglyceridemia. Although each of these abnormalities is probably related to atherosclerosis, it is unclear whether only one component and if so which one mediates most of the risk or whether the combination of lipidabnormalities is responsible for the excessive cardiovascular risk. Despite these uncertainties, current treatment recommendations focus on achieving a certain LDL-C goal.Therapeutic strategies include lifestyle changes, glucose control and specific lipid-lowering therapy. In most patients statin therapy should be the first choice, if a lipid lowering drug is indicated, as outcome data have proven their effectiveness in diabetic subjects. In patients with severe isolated hypertriglyceridemia fibrates may be used. In patients at very high risk, combination therapy to further lower LDL-C or to address LDL-C, HDL-C and triglycerides should be considered