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

Research Design and Methods: We conducted a nested case-control study, comparing 55 previously ART-naïve individuals who developed DM subsequent to 48 weeks after ART initiation (cases) to 55 individuals who did not develop DM during comparable follow-up (controls), matched on baseline BMI and race/ethnicity. Stored plasma at treatment initiation (week 0) and one year later (week 48) were assayed for levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), and the soluble receptors of tumor necrosis factor alpha (TNF-α) (sTNFR1 and sTNFR2).

Results: Cases were older than controls (median age: 41 vs 37 years, p=0.001), but the groups were otherwise comparable. Median levels for all markers, except hsCRP, decreased from week 0 to week 48. Subjects with higher levels of hsCRP, sTNFR1, and sTNFR2 at 48 weeks had an increased odds of subsequent DM, after adjustment for baseline marker level, age, BMI at week 48, CD4 count at week 48 (less than vs greater than 200 cells/mm³), and indinavir use (all p for 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% confidence interval; 1.28, 423, p-value=0.03).

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