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Abstract
Introduction In immune-mediated inflammatory diseases, there is a lack of -estimates of glucocorticoid dose–response diabetes risk that consider changes in prescribed dose over time and disease activity.
Research design and 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 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=6082), or systemic lupus erythematosus (n=4410). We estimated risks and HRs of type 2 diabetes associated with time-variant daily and total cumulative prednisolone-equivalent glucocorticoid dose using Cox regression methods.
Results Average patient age was 58.6 years, 65 469 (65.0%) were women and 8858 (22.6%) had a body mass index (BMI) ≥30 kg/m2. Overall, 8137 (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 ≥25.0 mg. 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 HR for a <5.0 mg daily dose versus non-use was 1.90, 95% CI 1.44 to 2.50; range 1.70 for rheumatoid arthritis to 2.93 for inflammatory bowel disease.
Conclusions 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.
- adverse drug reactions
- cohort
- adult diabetes
- glucocorticoid(s)
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Footnotes
JW and MP-R contributed equally.
Contributors JW and MP-R had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept, design, ethics approval, data acquisition and definitions of immune-mediated diseases and flares and covariates: MP-R. Definition of diabetes: MP-R and SLM. Creation of disease cohorts, exposure, outcomes and covariates: JW and MP-R. Management, analysis and interpretation of data: JW and MP-R. Drafting of the manuscript: MP-R. Critical revision of the manuscript for important intellectual content: JW and SLM. All authors approved the submission.
Funding 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 at Leeds. SLM was supported by an NIHR Clinician Scientist Fellowship.
Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Competing interests All authors declare no support from any organization 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 subinvestigatory 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.
Patient consent for publication Not required.
Ethics approval The Independent Scientific Advisory Committee (ISAC) for Medicines and Healthcare products Regulatory Agency database research approved the study (reference 16_146).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party and are not publicly available. Access to raw data can be requested from the CPRD (https://cprd.com).