Inflammatory stimulus may contribute to HIV lipodystrophy

Patients with HIV-associated lipodystrophy are likely to be severely insulin resistant, even when plasma glucose levels are within the normal range, report researchers from the State University of New York at Stony Brook. They also found that this syndrome is associated with elevated levels of soluble type 2 tumour necrosis factor (TNF)-alpha, suggesting that an inflammatory process may be responsible.

Dr. Dennis C. Mynarcik and associates measured insulin sensitivity and immune activation in 12 healthy control subjects, 14 HIV-infected patients without lipodystrophy and 15 HIV-infected patients with lipodystrophy. All subjects had normal random and fasting plasma glucose levels.

Severe insulin resistance, determined as the rate of glucose infused to maintain euglycemia during an insulin infusion, was demonstrated in those patients with pathologic loss of peripheral fat. Insulin resistance was highly correlated with soluble type 2 TNF-alpha. The cellular source of this cytokine is currently unknown.

The lipodystrophic subjects differed from subjects with diabetes in that fasting levels of insulin-like growth factor binding protein-1 were below normal. Trunk adipose tissue was not significantly associated with lipodystrophy and plasma levels of free fatty acids were normal, the investigators report in the December 1st issue of the Journal of Acquired Immune Deficiency Syndromes.

Dr. Mynarcik and his colleagues suggest that HIV-lipodystrophy resembles rare forms of acquired and congenital lipodystrophies. They emphasize that HIV-infected patients with fat redistribution and elevated triglyceride levels “be observed closely to prevent their progression to premature type 2 diabetes mellitus and coronary artery disease.”