Mechanisms and treatment of diabetic dyslipidemia
Type 2 diabetes and insulin resistance are associated with a complex change of metabolism of plasma lipoproteins that conveys a substantial part of increased cardiovascular (CV) risk of the diabetics. While quantity of lipoprotein particles (lipid concentrations) remain close to normal, their quality (composition) changes markedly. Lipoprotein metabolism in type 2 diabetes differs from normal at three levels. First, the production of very low-density lipoproteins (VLDLs) in the liver is elevated because of increased free fatty influx from enlarged intraabdominal adipose tissue mass. This leads to changes HDL metabolism as well as production of small dense LDL particles. Second, catabolism of lipoproteins decreases due to lower activity of lipolytic enzymes and receptor changes. Third, insulin resistance is associated with profound changes of lipoprotein assembly and trafficking in the enterocyte and, thus, postprandial lipoprotein metabolism.
Management of diabetic dyslipidemia must be based on a combination of lifestyle changes and pharmacotherapy together with maximum effort to achieve optimal diabetes control. Pharmacological treatment is based on a statin, which has been shown effective in all subgroups analysed. However, in statin-treated patients high rate of CV events has been documented and to impact on this residual risk a combination lipid-lowering treatment is necessary. Fibrates effectively reduce the risk of macrovascular complications in diabetics with hypertriglyceridemia and slow down microvascular changes. Niacin, despite its deteriorating impact on glucose homeostasis, leads to a broad and positive change of lipoprotein metabolism. Ezetimibe is as effective in diabetics as in non-diabetics, nevertheless, the data on its effects on vascular events is limited. Bile-acid sequestrants (resins) decrease levels of atherogenic lipoproteins and may even improve diabetes control.
Only comprehensive approach to diabetic dyslipidemia including lifestyle modification, proper control of diabetes and (combination) pharmacotherapy can reduce not only the levels of atherogenic lipoproteins but also cardiovascular risk of diabetics.