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Disease activity, cytokines, chemokines and the risk of incident diabetes in rheumatoid arthritis
  1. Joshua F Baker1,2,
  2. Bryant R England3,4,
  3. Michael George2,
  4. Grant Cannon5,
  5. Brian Sauer6,7,
  6. Alexis Ogdie2,
  7. Bartlett C Hamilton8,
  8. Carlos Hunter9,
  9. Michael J Duryee10,
  10. Geoffrey Thiele11,12,
  11. Ted R Mikuls13
  1. 1Rheumatology, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA, USA
  2. 2Departments of Medicine/Rheumatology and Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA
  3. 3Rheumatology, University of Nebraska Medical Center, Omaha, Nebraska, USA
  4. 4Rheumatology, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
  5. 5Rheumatology, VA Salt Lake City Health Care System, Salt Lake City, Utah, USA
  6. 6VA Salt Lake City Health Care System, Salt Lake City, Utah, USA
  7. 7University of Utah School of Medicine, Salt Lake City, Utah, USA
  8. 8University of Nebraska Medical Center and Omaha VA Medical Center, University of Nebraska, Omaha, Nebraska, USA
  9. 9University of Nebraska Medical Center, Omaha, Nebraska, USA
  10. 10Internal Medicine Division of Rheumatology, University of Nebraska System, Lincoln, Nebraska, USA
  11. 11Internal Medicine, University of Nebraska System, Lincoln, Nebraska, USA
  12. 12Research Service, 151, VAMC Omaha, Omaha, Nebraska, USA
  13. 13Department of Medicine, University of Nebraska System, Lincoln, Nebraska, USA
  1. Correspondence to Dr Joshua F Baker, Medicine, Rheumatology, University of Pennsylvania, Philadelphia, PA 19104, USA; bakerjo{at}


Purpose Rheumatoid arthritis (RA) is associated with a higher risk of diabetes mellitus (DM). Our aim was to determine associations between inflammatory disease activity (including evaluation of specific cytokines and chemokines) and incident DM.

Methods Participants were adults with physician-confirmed RA from Veteran’s Affairs Rheumatoid Arthritis Registry. Disease activity and clinical assessments occur longitudinally as part of clinical care. Thirty cytokines and chemokines were measured in banked serum obtained at the time of enrolment. Cytokine/chemokine values were log-adjusted and standardised (per SD). Incident DM was defined based on validated algorithms using diagnostic codes and medications. Multivariable Cox proportional hazard models evaluated associations between clinical factors and incident DM. Independent associations between cytokines/chemokines and incident DM were assessed adjusting for age, sex, race, smoking, body mass index (BMI) and medication use at baseline.

Results Among 1866 patients with RA without prevalent DM at enrolment, there were 130 incident cases over 9223 person-years of follow-up. High Disease Activity Score (DAS28)-C reactive protein (CRP), obese BMI, older age and male sex were associated with greater risk for incident DM while current smoking and methotrexate use were protective. Patients using methotrexate were at lower risk. Several cytokines/chemokines evaluated were independently associated (per 1 SD) with DM incidence including interleukin(IL)-1, IL-6 and select macrophage-derived cytokines/chemokines (HR range 1.11–1.26). These associations were independent of the DAS28-CRP.

Conclusions Higher disease activity and elevated levels of cytokines/chemokines are associated with a higher risk of incident DM in patients with RA. Future study may help to determine if targeted treatments in at-risk individuals could prevent the development of DM.

  • arthritis
  • rheumatoid
  • epidemiology
  • inflammation
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  • Handling editor Josef S Smolen

  • Presented at This work was presented at the 2019 American College of Rheumatology Annual meeting in Atlanta, GA (Abstract #839).

  • Contributors JFB was responsible for study concept, data acquisition, study design, analysis, data interpretation and scientific writing. BRE, GC and TRM were responsible for data acquisition, study design, data interpretation and scientific writing. MG, BS, AO, BCH, CH, MJD and GT were responsible for data interpretation, scientific writing. All authors had final approval of the manuscript.

  • Funding JFB is supported by a Veterans Affairs VA Merit Award (I01 CX001703). BRE is supported by the Rheumatology Research Foundation and the NIGMS (U54GM115458). TRM is supported by a VA Merit Award (I01 BX0046000) and grants from NIAAA (R25AA020818), NIGMS (U54GM115458) and NIAMS (P50AR60772).

  • Disclaimer The contents of this work do not represent the views of the Department of the Veterans Affairs or the US Government.

  • Competing interests JFB has received consulting fees from Bristol-Myers Squibb and Gilead.

  • Patient consent for publication Not required.

  • Ethics approval Each individual site has institutional review board approval.

  • Data availability statement Data may be obtained from a third party and are not publicly available. Data are not publicly available but may be requested from the VA Rheumatoid Arthritis Registry and Biorepository.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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