Interleukin-6, high sensitivity C-reactive protein, and the development of type 2 diabetes among HIV-positive patients taking antiretroviral therapy.
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.
Claude
C
Béténé A Dooko
Stephane
S
De Wit
Jacqueline
J
Neuhaus
Adrian
A
Palfreeman
Rosalie
R
Pepe
James S
JS
Pankow
James D
JD
Neaton
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment
D044966:Anti-Retroviral Agents; D015850:Interleukin-6; D002097:C-Reactive Protein