Disclosures: Baker reports consulting fees from Bristol Myers Squibb and Gilead Sciences, as well as support through a U.S. Veterans Affairs Merit Award. Please see the study for all other authors’ relevant financial disclosures.
January 14, 2021
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Higher RA disease activity, cytokine levels linked to diabetes risk

Disclosures: Baker reports consulting fees from Bristol Myers Squibb and Gilead Sciences, as well as support through a U.S. Veterans Affairs Merit Award. Please see the study for all other authors’ relevant financial disclosures.
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Higher disease activity and levels of cytokines or chemokines are associated with an increased risk for diabetes mellitus in patients with rheumatoid arthritis, according to data published in the Annals of the Rheumatic Diseases.

“Whether and how inflammation leads to the development of diabetes remains unclear and is an important question for patients with rheumatoid arthritis, who experience chronic inflammation over many years which might increase their risk,” Joshua F. Baker, MD, MSCE, of the University of Pennsylvania and the Philadelphia Veterans Affairs Medical Center, told Healio Rheumatology.

Image of arthritic hand
“Higher rheumatoid arthritis clinical disease activity as well as higher levels of circulating markers of inflammation in the blood were associated with a higher risk of developing diabetes in the future,” Joshua F. Baker, MD, MSCE, told Healio Rheumatology. Source: Adobe Stock

To analyze the link between inflammatory disease activity — including specific cytokines and chemokines — and the development of diabetes, Baker and colleagues studied adult patients with RA enrolled in the Veteran’s Affairs Rheumatoid Arthritis (VARA) Registry. According to the researchers, the VARA study is an ongoing national database established in 2003, with information from 13 participating VA centers. For their own study, Baker and colleagues included 1,866 VARA participants without diabetes at baseline in their longitudinal analysis.

The researchers assessed 30 cytokines and chemokines in banked serum obtained at VARA enrolment. Cytokine and chemokine values were then log-adjusted and standardized, per standard deviation. Meanwhile, incident diabetes was defined based on validated algorithms using diagnostic codes and medications. Baker and colleagues used multivariable Cox proportional hazard models to examine associations between clinical factors and incident diabetes, adjusting for age, sex, race, smoking, BMI and baseline medication use.

Joshua F. Baker

According to the researchers, there were 130 cases of incident diabetes during 9,223 person-years of follow-up. High Disease Activity Score (DAS28)-C reactive protein (CRP), obese BMI, older age and male sex were all associated with a greater risk for diabetes, while current smoking and methotrexate use were protective. Patients who used methotrexate demonstrated a lower risk for diabetes. Several cytokines and chemokines were independently associated — per 1 SD — with diabetes, including IL-1, IL-6 and select macrophage-derived cytokines or chemokines. These associations were independent of DAS28-CRP.

“Higher rheumatoid arthritis clinical disease activity as well as higher levels of circulating markers of inflammation in the blood were associated with a higher risk of developing diabetes in the future, even after accounting for differences in weight and other factors,” Baker told Healio Rheumatology.

“While our observational study is not definitive, it does suggest that better control of rheumatoid arthritis might help prevent this complication,” he added. “Further, it provides evidence of the importance of inflammation as a mechanism for the development of diabetes and might suggest that inflammation in other contexts — such as other autoimmune diseases — might also increase the risk of diabetes, though studies in those populations are needed.”

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