Pathogenesis of Atherogenic Dyslipidemia

Scott M. Grundy, MD, PhD.

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In This Article

Summary

Atherogenic dyslipidemia is a major component of the insulin resistance syndrome, and its presence signifies increased risk of CHD. The metabolic basis for atherogenic dyslipidemia is not fully understood; nonetheless, it seemingly derives from several abnormalities in lipid and lipoprotein regulation by the liver. Most notable in the development of atherogenic dyslipidemia is overproduction of VLDL particles, apo C-III, and hepatic lipase. These abnormalities almost certainly are the consequence of hepatic lipid overload. This overload in turn is derived largely from an elevation of plasma NEFA. Multiple causes of an increased plasma NEFA exist. Whole-body obesity is one cause. Another important cause is upper body obesity in which adipose tissue is unusually resistant to the action of insulin to suppress NEFA release. Some patients appear to be excessively insulin resistant, and atherogenic dyslipidemia develops with only mild degrees of obesity. These patients most likely have a genetic basis for their insulin resistance. Finally, rare patients have lipodystrophy; such patients are subject to severe hepatic lipid overload and atherogenic dyslipidemia.

Clinicians need to understand the role of dyslipidemia in the pathophysiology of the insulin resistance syndrome in order to help advance the diagnosis and effective treatment of these patients.

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