Higher Disease Activity Associated With Increased Risk for Diabetes in RA

Macrophage releasing cytokines
Researchers assessed the association between inflammatory disease activity and incident diabetes mellitus in patients with rheumatoid arthritis.

Among patients with rheumatoid arthritis (RA), greater disease activity and elevated cytokine/chemokine levels may be associated with a greater risk for incident diabetes mellitus (DM), according to study results published in Annals of the Rheumatic Diseases.

Previous studies have reported mixed data on the association between RA and the risk for DM, with several study findings suggesting that RA could be associated with a greater risk for DM and that certain therapies may reduce the risk.

The objective of the current study was to explore the association between RA disease activity, including assessment of specific cytokines and chemokines, and the risk of developing DM.

In the study, the researchers included adults with RA from the Veteran’s Affairs RA Registry. A total of 30 cytokines and chemokines were measured on banked serum from enrollment, and the risk for incident DM among patients with RA and no history of DM was analyzed by individual cytokine/chemokine levels after adjustment for age, sex, race, smoking, body mass index (BMI), and medication use.  

The total cohort included 1866 patients with RA and no history of DM at baseline. Of these patients, 130 developed DM during 9223 person-years of follow-up (1.41 cases per 100 person-years).

After adjustment for potential confounders, there was a dose-dependent association between disease activity and risk for DM, as higher disease activity, according to Disease Activity Score in 28 Joints with the C-reactive protein, was associated with a 2-fold increased risk for DM, compared with patients in remission (hazard ratio, 2.07; 95% CI, 1.34-2.85; P <.001).

While use of hydroxychloroquine and tumor necrosis factor inhibitors had no significant impact on the risk for DM, methotrexate use was associated with a lower risk for DM. Risk for DM was also lower among women and current smokers. Higher BMI was an important risk factor for DM, and a BMI greater than 35 vs a normal BMI was associated with more than a 6-fold increased risk for DM (P <.001).

Of the cytokines and chemokines analyzed in this study, interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-12p70, IL-15, macrophage-derived chemokine, macrophage chemoattractant protein-1, macrophage chemoattractant protein-4, macrophage inflammatory protein-1β, macrophage inflammatory protein-3α, and eotaxin were each independently and significantly associated with risk for DM (hazard ratio per SD range, 1.11-1.26; P <.05).

The study had several limitations, including the sample size that limited the ability to identify a weaker association of specific cytokines and chemokines with the outcome, the strong interanalyte correlation that limited the ability to identify key cytokines with a pathogenic role, and no available data on the impact of changes in cytokines and chemokines over time.

“These data support closer attention to the risk [for] diabetes among patients with elevated disease activity and may support more aggressive treatment to reduce the risk,” the researchers concluded.

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for the author’s disclosures.


Baker JF, England BR, George M, et al. Disease activity, cytokines, chemokines and the risk of incident diabetes in rheumatoid arthritis. Ann Rheum Dis. Published online January 4, 2021. doi:10.1136/annrheumdis-2020-219140