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Fasting Hyperinsulinemia and Changes in Regional Body Composition in Human Immunodeficiency Virus-Infected Women¹

Neuroendocrine Unit (K.M., C.C., S.G.), Combined Program in Pediatric Gastroenterology and Nutrition (C.H.), General Clinical Research Center (E.A.) and Infectious Disease Unit (N.B.), Massachusetts General Hospital, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Steven Grinspoon, M.D., Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: sgrinspoon{at}partners.org

A novel lipodystrophy syndrome (characterized by insulin resistance, hypertriglyceridemia, and fat redistribution) has recently been described in human immunodeficiency virus (HIV)-infected patients. However, investigation of the lipodystrophy syndrome has generally been limited to men; and a comprehensive evaluation of insulin, lipids, and regional body composition has not been performed in the expanding population of HIV-infected women. In this study, we assessed fasting insulin, lipid levels, virologic parameters, and regional body composition, using dual-energy x-ray absorptiometry, in a cohort of 75 HIV-infected women (age, 25–46 yr), in comparison with 30 healthy weight-matched premenopausal control subjects. HIV-infected women demonstrated significant truncal adiposity (38.5 ± 0.9 vs. 34.9 ± 1.3%, P < 0.05) hyperinsulinemia (15.9 ± 1.5 vs. 7.5 ± 0.6 µU/mL, P < 0.001) and an increased insulin-to-glucose ratio (0.2 ± 0.02 vs. 0.1 ± 0.03, P < 0.001), compared with control subjects. Insulin and the insulin-to-glucose ratio were increased, even among HIV-infected patients with low body weight (<90% of ideal body weight) (insulin, 13.3 ± 2.8 µU/mL, P < 0.01 vs. control; insulin/glucose, 0.2 ± 0.04, P < 0.01 vs. control). Insulin and the insulin-to-glucose ratio were most significantly elevated among patients with increased truncal adiposity (insulin, 28.2 ± 3.2 µU/mL, P < 0.001 vs. control; insulin/glucose, 0.32 ± 0.04, P < 0.001 vs. control). In contrast, no differences in insulin were seen in relation to protease inhibitor (PI) use. Similarly, HIV-infected women also demonstrated significant hypertriglyceridemia (144 ± 15 vs. 66 ± 23 mg/dL, P < 0.01 vs. controls), which was present even among low-weight patients (148 ± 32 mg/dL, P < 0.001 vs. control) but was not related to truncal adiposity or PI usage. These data demonstrate significant hyperinsulinemia and truncal adiposity in HIV-infected women. Our data suggest that these metabolic abnormalities occur at baseline in HIV-infected women, independent of PI use. However, these data do not rule out a direct effect of PI therapy on fat metabolism or indirect effects of PI therapy to further worsen glucose and lipid homeostasis in association with weight gain and disease recovery.

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