Insulin Resistance and Lipid Disorders

Roberto Miccoli; Cristina Bianchi; Giuseppe Penno; Stefano Del Prato


Future Lipidology. 2008;3(6):651-664. 

In This Article

Abstract and Introduction


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.


Insulin resistance is a common condition that is believed to play a main role in the pathogenesis of the metabolic syndrome (MS), obesity and Type 2 diabetes (T2DM), as well as cardiovascular disease.[1] The prevalence of all these conditions is growing at an unexpected rate, probably owing to exacerbation of insulin resistance as a consequence of increased caloric intake and decreased energy expenditure. Recent studies have suggested that lifestyle modification, based on weight reduction and increased physical activity, can prevent or delay development of T2DM and MS in high-risk subjects.[2] Weight reduction and an improvement in fitness are both associated with significant amelioration of insulin sensitivity, supporting a strong link between impaired insulin action and metabolic/cardiovascular diseases. The possibility that insulin resistance may play a central role in the clustering of multiple cardiovascular risk factors was initially proposed by Reaven when he noticed how often insulin-resistance was associated with impaired glucose tolerance, hypertension and dyslipidemia.[3] Subsequently, the mechanisms relating impaired insulin action with components of the MS have been explored. It is the purpose of this review to provide an overview of the mechanisms through which insulin resistance (and concomitant hyperinsulinemia) leads to alteration of circulating lipoproteins. However, dyslipidemia is just an aspect of a more generalized disturbance of lipid metabolism associated with insulin resistance. Common to this condition is accretion of lipids in adipose tissue (particularly at the visceral level) as well as outside the adipose tissue (i.e., ectopic accumulation in liver, muscle, pancreas, heart and vessels). Therefore, this review will also provide a comprehensive approach to explore how ectopic lipid accumulation, lipotoxicity and altered lipoprotein metabolism may all be entangled to generate increased cardiovascular risk.


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