Insulin Resistance and Lipid Disorders

The dyslipidemia of insulin resistance is characterized by elevated levels of triglycerides (TGs), low HDL-cholesterol and small dense LDL particles. Many of these features are affected by the reduction in insulin sensitivity, with a central role played by abnormalities in assembly and secretion of VLDL. Postprandial hyperlipidemia is common in insulin-resistant individuals, probably owing to reduced lipolysis of nascent chylomicrons. Increased exchange of HDL cholesteryl esters for TGs is associated with lipolysis of HDL-TG by hepatic lipase and this produces dysfuntional particles that are less stable than normal particles and contribute to decreased reverse cholesterol transport. On the other hand, TG accumulation has been described as dangerous for several tissues, the so-called lipotoxicity, particularly for pancreatic β-cells where it results in impairment of glucose-stimulated insulin secretion and accelerated apoptosis. Recently, islet dysfunction and loss of insulin secretion have also been associated with alterations of plasma and islet cholesterol levels. A more comprehensive appreciation of reciprocal effects of insulin resistance and atherogenic dyslipidemia should guide the physician in a more conscious therapeutic decision.