Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy

Diabetes Care. 2010 Oct;33(10):2244-9. doi: 10.2337/dc10-0633. Epub 2010 Jul 27.


Objective: To determine whether systemic inflammation after initiation of HIV-antiretroviral therapy (ART) is associated with the development of diabetes.

Research design and methods: We conducted a nested case-control study, comparing 55 previously ART-naive individuals who developed diabetes 48 weeks after ART initiation (case subjects) with 55 individuals who did not develop diabetes during a comparable follow-up (control subjects), matched on baseline BMI and race/ethnicity. Stored plasma samples at treatment initiation (week 0) and 1 year later (week 48) were assayed for levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and the soluble receptors of tumor necrosis factor-α (sTNFR1 and sTNFR2).

Results: Case subjects were older than control subjects (median age 41 vs. 37 years, P = 0.001), but the groups were otherwise comparable. Median levels for all markers, except hs-CRP, decreased from week 0 to week 48. Subjects with higher levels of hs-CRP, sTNFR1, and sTNFR2 at 48 weeks had an increased odds of subsequent diabetes, after adjustment for baseline marker level, age, BMI at week 48, CD4 count at week 48 (< vs. >200 cells/mm(3)), and indinavir use (all P(trend) ≤ 0.05). After further adjustment for week 48 glucose, effects were attenuated and only sTNFR1 remained significant (odds ratio, highest quartile vs. lowest 23.2 [95% CI 1.28-423], P = 0.03).

Conclusions: Inflammatory markers 48 weeks after ART initiation were associated with increased risk of diabetes. These findings suggest that systemic inflammation may contribute to diabetes pathogenesis among HIV-infected patients.

Publication types

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

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / etiology*
  • Diabetes Mellitus, Type 2 / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • Humans
  • Inflammation / physiopathology*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • Tumor Necrosis Factor-alpha / blood


  • Anti-Retroviral Agents
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein