Higher CD163 levels are associated with insulin resistance in hepatitis C virus-infected and HIV-infected adults
Year: 2016
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: HIV/hepatitis C virus (HCV) coinfection is associated with insulin resistance, but the mechanism is unclear. We hypothesized that intestinal epithelial damage and the consequent monocyte/macrophage activation and inflammation explain this perturbation. DESIGN: Cross-sectional study of 519 adults (220 HIV+/HCV-; 64 HIV-/HCV+; 89 HIV+/HCV+; 146 HIV-/HCV-). METHODS: We used multivariable linear regression to evaluate associations of HIV and HCV with the homeostasis model assessment of insulin resistance (HOMA-IR) and if intestinal fatty (FA) acid binding protein (I-FABP, a marker of gut epithelial integrity), soluble CD14 (sCD14) and soluble CD163 (sCD163) (markers of monocyte/macrophage activation), and IL-6 (an inflammatory cytokine) mediated this association. RESULTS: HIV+/HCV+ and HIV-/HCV+ had greater demographic-adjusted HOMA-IR [mean (95% confidence interval (CI)): 1.96 (1.51, 2.54) and 1.65 (1.22, 2.24)] than HIV+/HCV- and HIV-/HCV-[1.41 (1.18, 1.67) and 1.44 (1.17, 1.75), respectively]. After additional adjustment for lifestyle and metabolic factors, HIV+/HCV+ remained associated with 36% (95% CI: 4, 80%) greater HOMA-IR relative to HIV-/HCV-, whereas HIV-/HCV+ and HIV+/HCV- had smaller differences. Adjustment for sCD163 substantially attenuated the difference between HIV+/HCV+ and HIV-/HCV-; adjustment for I-FABP, sCD14, and IL-6 had little effect. Higher sCD163 was independently associated with 19% (95% CI: 7, 33%), 26% (95% CI: 15, 39%), 25% (95% CI: 14, 37%), and 23% (95% CI: 11, 36%) greater HOMA-IR in HIV+/HCV+, HIV-/HCV+, HIV+/HCV-, and HIV-/HCV- (all estimates per doubling of sCD163). I-FABP, sCD14, and IL-6 were not associated with HOMA-IR. CONCLUSION: HIV/HCV coinfection is associated with greater HOMA-IR, even after controlling for demographic, lifestyle, and metabolic factors. sCD163, which appears independent of intestinal epithelial damage and inflammation, partly explains this association. Our findings that the association of sCD163 with HOMA-IR occurred even in the absence of HIV and HCV, indicate that viral and nonviral factors affect sCD163 levels. Its role in insulin resistance needs elucidation.
Source: AIDS
Language: English
Topic: Hepatitis C virus research
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, American College of Gastroenterology, Northern California Institute for Research and Education, Georgia Clinical and Translational Science Alliance, National Institutes of Health, Center for AIDS Research, University of Washington, University of California, San Francisco, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, Office of Research on Women's Health, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1047576501, G1252706584, G1255407591, G1360453192, G1377681116, G1423343497, G1440661678, G1653728403, G1689765846, G1919789535, G2034299771, G2037985070, G208418196, HIV, HCV, and gender effects on Liver, Bone, and Vascular Health, Emory WIHS CRS - Longitudinal Cohort, G2574405597, G2692709432, G2800002786, G2839755957, Visceral Adiposity, HIV, and HCV: Biologic Mediators of Hepatic Steatosis, G2889922178, G3009646583, G3079921036, G316338625, G3181090803, G3212103026, The Connie Wofsy Women's HIV Study, Brooklyn Women's Interagency HIV Study (WIHS) V, G3634354056, Miami Womens Interagency HIV Study WIHS, G4371267688, G4419450409, WIHS Data Management and Analysis Center (WDMAC), G4541905479, G4804712267, G4897434353, G499585988, G5182092287, G5282551706, G5514441876, Washington Women's Interagency HIV/AIDS Study, Clinical and Translational Science Institute, G5909718580, Atlanta Clinical and Translational Science Institute (ACTSI) Renewal, G6212232794, G6295786800, G6694807131, G6990385686, University of North Carolina Womens Interagency HIV Study UNC WIHS, G767062161, G775892330, G7807729167, Women's Interagency HIV Study (WIHS-V), G826976987, G8350406629, G8846374971, UAB-MISS WIHS Cohort, G893076474, G8964979204, G9000034972, G9000059561, G9000073987, G9000078127, G9000080293, G9000122276, G9000237332, G9000338758, UCSF Liver Center, Traineeships in AIDS Prevention Studies, Center for AIDS Prevention Studies (CAPS), UCSF-Bay Area Center for AIDS Research, G920507375, G925273713, G976727283
OpenAlex ID: W2560848402