Immunosuppressive treatment and the risk of diabetes in rheumatoid arthritis.

Siri Lillegraven,Dimitrios A Pappas,Leslie Harrold,Jeffrey D Greenberg,Joel M Kremer,George W Reed,Marc C Hochberg,Jeffrey R Curtis,Daniel H Solomon,Katherine Saunders

doi:10.1371/journal.pone.0210459

Abstract

ObjectiveInflammation and anti-inflammatory treatments might influence the risk of diabetes. The objective of this study was to assess factors associated with incident diabetes in rheumatoid arthritis (RA).MethodsThe study population consisted of RA patients from a multi-center cohort study, Corrona. To assess risk associated with disease modifying antirheumatic drug (DMARD) exposure, we assessed five mutually exclusive DMARD groups. Additionally, we assessed the risk associated with body mass index (BMI, <25, 25–30, >30 kg/m2) and glucocorticoid usage. Incident cases of diabetes were confirmed through adjudication, and Cox regression models were fit to estimate the risk of incident diabetes.ResultsWe identified 21,775 DMARD treatment regimens, the mean (SD) age at the index visit was 58 (13) years, disease duration 10 (10) years, and 30% used oral glucocorticoids at the time. Eighty-four incident cases of diabetes were confirmed within the treatment exposure periods. The hazard ratio (HR, 95% confidence interval) for diabetes was significantly reduced in patients receiving TNF inhibitors, HR 0.35 (0.13, 0.91), compared to patients treated with non-biologic DMARDs other than hydroxychloroquine and methotrexate. Hydroxychloroquine, methotrexate and use of other biologic DMARDs had a numerically reduced risk compared to the same group. Patients prescribed ≥7.5 mg of glucocorticoids had a HR of 2.33 (1.68, 3.22) of incident diabetes compared with patients not prescribed oral glucocorticoids. RA patients with a BMI >30 had a HR of 6.27 (2.97, 13.25) compared to patients with BMI ≤25.ConclusionDMARDs, glucocorticoids and obesity influenced the risk of incident diabetes in a large cohort of RA patients. Monitoring for the occurrence of diabetes should be part of routine RA management with a focus on specific subgroups.

Highlights

Rheumatoid arthritis (RA) is a systemic inflammatory disease, characterized by joint pain, loss of function and decreased quality of life [1]
The hazard ratio (HR, 95% confidence interval) for diabetes was significantly reduced in patients receiving Tumor necrosis factor (TNF) inhibitors, HR 0.35 (0.13, 0.91), compared to patients treated with non-biologic disease modifying antirheumatic drug (DMARD) other than hydroxychloroquine and methotrexate
DMARDs, glucocorticoids and obesity influenced the risk of incident diabetes in a large cohort of RA patients

Summary

Introduction

Rheumatoid arthritis (RA) is a systemic inflammatory disease, characterized by joint pain, loss of function and decreased quality of life [1]. RA patients increasingly receive treatment tailored to their disease activity, co-morbidities and predictors of subsequent joint damage and loss of function. RA is associated with abnormalities in the glucose metabolism, mainly insulin resistance, a precursor to type 2 diabetes [5, 6], and data suggest an increased occurrence of diabetes in RA patients, studies are somewhat conflicting [7,8,9]. Blockade of interleukin-1 with the drug anakinra has been shown to improve glycemia and beta-cell secretory function in patients with type 2 diabetes [12]. Obesity represents the main risk factor for diabetes; it correlates with higher RA disease activity, more disability and an increased risk of comorbidities in RA [13, 14]

Methods

Results

Conclusion