HIV-
lipodystrophy (HIV-LD) is characterized by the loss of body fat from the limbs and face, an increase in truncal fat,
insulin resistance, and
hyperlipidemia, factors placing affected patients at increased risk for
vascular disease. This study evaluated
insulin sensitivity and inflammatory status associated with HIV-LD and provides suggestions about its etiology.
Insulin sensitivity and immune activation markers were assessed in 12 control subjects and 2 HIV-positive groups, 14 without and 15 with LD syndrome. Peripheral
insulin sensitivity (mostly skeletal muscle) was determined with the hyperinsulinemic-euglycemic clamp. Circulating
insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) and
free fatty acid (FFA) levels, and their response to
insulin infusion were indicative of
insulin responsiveness of liver and adipose tissue, respectively. Serum levels of soluble type 2
tumor necrosis factor-alpha (
TNF-alpha) receptor (sTNFR2) were used as an
indicator of immune activation. HIV-LD study subjects had significantly reduced (twofold) peripheral
insulin sensitivity, but normal levels of FFA and reduced levels of
IGFBP-1, relative to the nonlipodystrophy groups, indicating that the loss of
insulin sensitivity was more pronounced in skeletal muscle than in liver or fat. The significant loss of peripheral fat in the HIV-LD group (34%; p <.05) closely correlated with the reduced peripheral
insulin sensitivity (p =. 0001). Levels of sTNFR2 were elevated in all HIV-infected study subjects, but they were significantly higher in those with
lipodystrophy than without, and sTNFR2 levels strongly correlated with the reduction in
insulin sensitivity (p =.0001). Loss of peripheral fat, normal levels of FFA, and reduced levels of
IGFBP-1 indicate that
insulin resistance in HIV-LD is distinct from
type 2 diabetes and
obesity. The relationship between the degree of
insulin resistance and sTNFR2 levels suggests an inflammatory stimulus is contributing to the development of
HIV-associated lipodystrophy.