Hypoadiponectinemia Is Associated with Insulin Resistance, Hypertriglyceridemia, and Fat Redistribution in Human Immunodeficiency Virus-Infected Patients Treated with Highly Active Antiretroviral Therapy
Carol L. Addy,
Alina Gavrila,
Sotirios Tsiodras,
Kimberly Brodovicz,
Adolf W. Karchmer and
Christos S. Mantzoros
Department of Internal Medicine (C.L.A.), Endocrinology-Hypertension Division, Brigham and Women’s Hospital, Boston, Massachusetts 02115; Divisions of Endocrinology and Metabolism (C.L.A., A.G., C.S.M.) and Infectious Diseases (S.T., A.W.K.), Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215; and Merck Research Laboratories (K.B.), Blue Bell, Pennsylvania 19422
Address all correspondence and requests for reprints to: Christos S. Mantzoros, M.D., Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, RN 325A, Boston, Massachusetts 02215. E-mail: cmantzor{at}caregroup.harvard.edu.
A lipodystrophic syndrome and metabolic abnormalities have beenobserved in HIV-infected patients treated with highly activeantiretroviral therapy (HAART). A murine model of lipodystrophyis associated with decreased levels of adiponectin, an adipocyte-secretedprotein, the administration of which improves the metabolicsyndrome in these mice. To investigate the association of adiponectinwith metabolic changes in human lipodystrophy, we conducteda cross-sectional study of 112 HIV-infected patients treatedwith HAART.
Mean adiponectin levels were higher in patients with no fatredistribution (FR) vs. FR (4.8 ± 5.0 vs. 2.2 ±2.7 µg/ml, P < 0.01), but no significant differencesin adiponectin levels were observed between FR subgroups. Thedifference in adiponectin levels between subjects with and withoutFR remained significant after adjusting for age, gender, leptin,HIV medication use, and CD4 count using logistic regression(odds ratio, 0.54, P = 0.008). Adiponectin was significantlycorrelated with triglycerides (r = -0.40), abdominal visceralfat (r = -0.35), extremity fat (r = 0.37), insulin resistance(HOMA-IR) (r = -0.28), nucleoside reverse transcriptase inhibitor(NRTI) use (r = -0.32), and high-density lipoprotein (HDL) (r= 0.41) using bivariate analysis (all P < 0.01). The associationwith HDL weakened but remained significant on multivariate analysis(standard ß = 0.29, P = 0.01). However, the associationof adiponectin with HOMA-IR became nonsignificant after adjustingfor NRTI use (standard ß = -0.15, P = 0.12), suggestingthat changes in adiponectin levels may underlie the effect ofNRTI use on insulin resistance. The associations of adiponectinwith triglycerides and HOMA-IR were also slightly weakened afteradjusting for visceral and extremity fat, indicating that adiponectinmay, in part, mediate the effect of FR on triglycerides andinsulin resistance.
This study indicates that adiponectin is inversely correlatedwith abdominal visceral fat mass, serum triglycerides, and insulinresistance and is directly correlated with HDL and extremityfat in a sample of HIV-infected patients treated with HAART.The results also indicate that NRTI use may worsen insulin resistanceby decreasing adiponectin levels. Thus, adiponectin replacementmay be a potential treatment option to ameliorate the metabolicchanges observed in this patient population.
This work was supported by an American Diabetes AssociationClinical Research Grant and NIH Grant DK-58785-R01 (to C.S.M.),NIH Grant M01-RR 01032 (to BIDMC General Clinical Research Center),NIH Grant K30-HL04095 (to Harvard Medical School), and MerckResearch Laboratories.
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