Interleukin-6, high sensitivity C-reactive protein, and the development of type 2 diabetes among HIV-positive patients taking antiretroviral therapy

J Acquir Immune Defic Syndr. 2014 Dec 15;67(5):538-46. doi: 10.1097/QAI.0000000000000354.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • C-Reactive Protein / analysis*
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / pathology*
  • Humans
  • Interleukin-6 / blood*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Risk Assessment


  • Anti-Retroviral Agents
  • Interleukin-6
  • C-Reactive Protein