Background: HIV infection is associated with increased levels of inflammatory markers. Inflammation is hypothesized to play a role in the development of type 2 diabetes. Data addressing this issue among HIV-positive participants are limited.
Methods: A cohort of 3695 participants without diabetes, taking antiretroviral therapy and with an average CD4+ count of 523 cells/mm3, were followed for an average of 4.6 years. Diabetes risk associated with baseline levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) was assessed using Cox proportional hazards regression models. Analyses considered baseline levels of factors associated with diabetes risk and HIV-related measures.
Results: One hundred thirty-seven patients developed diabetes requiring drug treatment during follow-up (8.18 per 1000 person-years). Median levels of IL-6 and hsCRP were significantly higher among those who developed diabetes compared with those who did not: 3.45 versus 2.50 pg/mL for IL-6 and 4.91 versus 3.29 µg/mL for hsCRP (P < 0.001). Adjusted hazard ratios associated with a doubling of IL-6 and hsCRP were 1.29 (95% confidence interval: 1.08 to 1.55; P = 0.005) and 1.22 (95% confidence interval: 1.10 to 1.36; P < 0.001), respectively. Body mass index (P < 0.001), age (P = 0.013), coinfection with hepatitis B or C (P = 0.03), nonsmoking status (P = 0.034), and use of lipid-lowering treatment (P = 0.008) were also associated with an increased risk of diabetes.
Conclusions: These findings indicate that low-grade systemic inflammation is an underlying factor in the pathogenesis of diabetes.
*Department of Health Care Economics, UCare, Minneapolis, Minnesota, United States;
†Department of Infectious Diseases, St Pierre University Hospital, Brussels, Belgium;
‡Division of Biostatistics, University of Minnesota, Minnesota, United States;
§Department GU Medicine, University Hospitals, Leicester, United Kingdom;
‖Division of Infectious Disease, Cooper University Hospital, Camden, New Jersey, United States; and
¶Division of Epidemiology and Community Health, University of Minnesota, Minnesota, United States.
Correspondence to: Claude Béténé A Dooko, DVM, MPH, 710 Pelham Boulevard, Apartment 1, Saint Paul, MN 55114 (e-mail: email@example.com).
Supported by the National Institute of Allergy and Infectious Diseases (NIAID). The SMART and ESPRIT studies were funded by NIAID [grant numbers U01AI042170 and U01AI046362 (SMART); U01AI46957 and U01AI068641 (ESPRIT)].
The authors have no conflicts of interest to disclose.
All the authors provided input to drafts of the manuscript.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).
Received April 16, 2014
Accepted August 11, 2014