Glucocorticoid Dose-Dependent Risk of Type 2 Diabetes in Six Immune-Mediated Inflammatory Diseases: A Population-Based Cohort Analysis

Abstract

Background: In immune-mediated inflammatory diseases, there is a lack of precise estimates of glucocorticoid dose-response diabetes risk that consider changes in prescribed dose over time and disease activity. Methods: Population-based longitudinal analysis of electronic health records from the UK Clinical Practice Research Datalink, linked to hospital admissions and the mortality registry (1998-2017). We included 100,722 adult patients without prior diabetes history, diagnosed with giant cell arteritis or polymyalgia rheumatica (n=32,593), inflammatory bowel disease (n=29,272), rheumatoid arthritis (n=28,365), vasculitis (n=6,082), or systemic lupus erythematosus (n=4,410). We estimated risks and hazard ratios of type 2 diabetes associated with time-variant daily and total cumulative prednisolone-equivalent glucocorticoid dose using Cox regression methods. Findings: Average patient age was 58·6 years, 65,469 (65·0%) were women and 8,858 (22·6%) had a BMI ≥30 kg/m2. Overall, 8,137 (8·1%) people developed type 2 diabetes after a median follow-up of 4·9 years. At 1 year, the cumulative risk of diabetes increased from 0·9% during periods of non-use to 5·0% when the daily prednisolone-equivalent dose was ≥25·0mg. We found strong dose-dependent associations for all immune-mediated diseases, BMI levels and underlying disease duration, even after controlling for periods of active systemic inflammation. Adjusted hazard ratio [HR] for a <5·0mg daily dose vs. non-use was 1·90, 95%CI 1·44-2·50; range 1·70 for rheumatoid arthritis to 2·93 for inflammatory bowel disease. Interpretation: We report dose-dependent risks of type 2 diabetes associated with glucocorticoid use for six common immune-mediated inflammatory diseases. These results underline the need for regular diabetic risk assessment and testing during glucocorticoid therapy in these patients. Funding Statement: This work was partly supported by the Medical Research Council TARGET Partnership Grant (Treatment According to Response in Giant cEll arTeritis) (MR/N011775/1). JW is supported by the NIHR infrastructure @ Leeds. SLM was supported by a NIHR Clinician Scientist Fellowship. Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare no support from any organisation for the submitted work except for SLM who received: salary support from NIHR (Clinician Scientist Fellowship) during the period of work reported here; advisory board fees from Roche in 2015 and conference attendance from Roche in 2019; investigator or sub-investigatory on industry-sponsored clinical trials (Sanofi, Roche, GSK) and consultancy on behalf of the University of Leeds (without receiving personal income) to Roche and Sanofi. SLM is Patron of the patient support charity PMRGCAuk. Ethics Approval Statement: The Independent Scientific Advisory Committee for Medicines and Healthcare products Regulatory Agency database research (ISAC) approved the study (reference 16_146).