Abstract
OBJECTIVE: To quantify the risk of incident diabetes mellitus (DM) associated with the dosage, duration, and timing of glucocorticoid (GC) use in patients with rheumatoid arthritis (RA). METHODS: We undertook a cohort study using 2 databases: a UK primary care database (the Clinical Practice Research Datalink [CPRD]) including 21,962 RA patients (1992-2009) and the US National Data Bank for Rheumatic Diseases (NDB) including 12,657 RA patients (1998-2013). Information on the dosage and timing of GC use was extracted. DM in the CPRD was defined using Read codes, at least 2 prescriptions for oral antidiabetic medication, or abnormal blood test results. DM in the NDB was defined through patient self-reports. Data were analyzed using time-dependent Cox models and a novel weighted cumulative dose (WCD) model that accounts for dosage, duration, and timing of treatment. RESULTS: The hazard ratio (HR) was 1.30 (95% confidence interval [95% CI] 1.17-1.45) and 1.61 (95% CI 1.37-1.89) in current GC users compared to nonusers in the CPRD and the NDB, respectively. A range of conventional statistical models consistently confirmed increases in risk with the GC dosage and duration. The WCD model showed that recent GC use contributed the most to the current risk of DM, while doses taken >6 months previously did not influence current risk. In the CPRD, 5 mg of prednisolone equivalent dose for the last 1, 3, and 6 months was significantly associated with HRs of 1.20, 1.43, and 1.48, respectively, compared to nonusers. CONCLUSION: GC use is a clinically important and quantifiable risk factor for DM. Risk is influenced by the dosage and treatment duration, although only for GC use within the last 6 months.