Insulin resistance and lipid disorders

The dyslipidemia of insulin resistance is characterized by elevated levels oftriglycerides (TGs), low HDL-cholesterol and small dense LDL particles. Many ofthese features are affected by the reduction in insulin sensitivity, with a centralrole played by abnormalities in assembly and secretion of VLDL. Postprandialhyperlipidemia is common in insulin-resistant individuals, probably owing toreduced lipolysis of nascent chylomicrons. Increased exchange of HDLcholesteryl esters for TGs is associated with lipolysis of HDL-TG by hepatic lipaseand this produces dysfuntional particles that are less stable than normalparticles and contribute to decreased reverse cholesterol transport. On theother hand, TG accumulation has been described as dangerous for severaltissues, the so-called lipotoxicity, particularly for pancreatic β-cells where itresults in impairment of glucose-stimulated insulin secretion and acceleratedapoptosis. Recently, islet dysfunction and loss of insulin secretion have alsobeen associated with alterations of plasma and islet cholesterol levels. A morecomprehensive appreciation of reciprocal effects of insulin resistance andatherogenic dyslipidemia should guide the physician in a more conscious therapeutic decision.