Dose–Response Association Between Systemic and Dermatologic Glucocorticoid Use and Type 2 Diabetes Mellitus: A Nationwide Case–Control Study

AIMS: To investigate the association and dose-response between systemic and topical glucocorticoids and odds of Type 2 diabetes mellitus. MATERIALS AND METHODS: We conducted a nationwide case-control study using Danish registry data from 2013 to 2021. People aged 40 years or older with incident type 2 diabetes mellitus (n = 149 113) were matched 1:3 with controls (n = 447 339) by age, sex and weighted Charlson Comorbidity Index. Glucocorticoid exposure was defined as ≥ 1 prescription within 1 year before the date of diagnosis and ≥ 2 within 3 years and classified as systemic or topical. Conditional logistic regression estimated ORs with 95% CIs, and dose-response associations were assessed according to daily prednisolone-equivalent dose. RESULTS: Incident Type 2 diabetes mellitus cases had higher glucocorticoid exposure and cumulative doses than controls among oral systemic and dermatologic glucocorticoids. Odds increased progressively with higher doses of oral systemic glucocorticoids: adjusted OR 1.25 (95% CI, 1.21-1.29) at < 2.5 mg/day; 1.49 (95% CI, 1.43-1.56) at 2.5-7.4 mg/day; and 3.02 (95% CI, 2.90-3.15) at ≥ 7.5 mg/day. Dermatologic glucocorticoids showed a similar gradient, from 1.21 (95% CI, 1.18-1.23) at < 2.5 mg/day to 1.51 (95% CI, 1.40-1.63) at ≥ 7.5 mg/day. No progressively significant associations were observed for nasal, rectal, ophthalmic or otic formulations after adjustment. CONCLUSION: Systemic and dermatologic glucocorticoid use was associated with a clear dose-dependent increase in Type 2 diabetes mellitus odds, including at doses < 2.5 mg/day. Other topical routes appeared metabolically safe. Consideration of cumulative glucocorticoid exposure should inform prescribing and monitoring practices.