Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy.
OBJECTIVE
To determine whether systemic inflammation after initiation of HIV-antiretroviral therapy (ART) is associated with the development of diabetes.


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.
Brown
Todd T
TT
Division of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, Maryland, USA. tbrown27@jhmi.edu
Tassiopoulos
Katherine
K
Bosch
Ronald J
RJ
Shikuma
Cecilia
C
McComsey
Grace A
GA
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D044966:Anti-Retroviral Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein