Topical Corticosteroids and the Risk of Diabetes Mellitus A Nested Case-Control Study in the Netherlands

• Published in: Drug safety Vol. 32; no. 6; pp. 527 - 537
• Main Authors: van der Linden, Michiel W., Beest, Fernie J. A. Penning-van, Nijsten, Tamar, Herings, Ron M. C.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-01-2009; Adis International; Wolters Kluwer Health, Inc; Springer Nature B.V
• Subjects: Administration, Topical; Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - adverse effects; Adult; Aged; Biological and medical sciences; Case-Control Studies; Clinical trial. Drug monitoring; Complications and side effects; Corticosteroids; Diabetes; Diabetes Mellitus - chemically induced; Diabetes. Impaired glucose tolerance; Dosage and administration; Drug Safety and Pharmacovigilance; Drug toxicity and drugs side effects treatment; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; General pharmacology; Humans; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Netherlands; Original Research Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Risk; Risk factors; Netherlands; Europe; Index Date; Fluticasone Propionate; Atopic Dermatitis; Topical Corticosteroid; Systemic Corticosteroid; Endocrinopathy; Human; Corticosteroid; Local administration; Toxicity; Diabetes mellitus; Risk factor; Secondary effect; Case control study; Pharmacovigilance; Topical administration
• ISSN: 0114-5916; 1179-1942
• DOI: 10.2165/00002018-200932060-00008

Background:
The relationship between topical corticosteroid use, potency, treatment duration, concomitant exposure to systemic corticosteroids, and risk of diabetes has been incompletely studied.
Objective:
To investigate an association between intense, longstanding topical corticosteroid use and diabetes mellitus.
Methods:
Data for this nested case-control study were obtained from the PHARMO Record Linkage System, including linked drug dispensing and hospital records of >2.5 million individuals in defined areas of the Netherlands. Users of topical corticosteroids during 1992–2004, without diabetes, with ≥2 topical corticosteroid dispensings and ≥4 years of follow-up were selected. Diabetes onset was defined as first occurrence (index date) of an antidiabetic drug dispensing or hospitalization for diabetes. Cases were matched 1:4 by age and sex to controls, with ≥2 topical corticosteroid dispensings and similar follow-up duration. Use of topical corticosteroids and systemic corticosteroids and/or inhaled corticosteroids as co-medication was classified as current, recent and past/never (≤2 years, 2–4 years and >4 years ago, respectively). Multivariate regression analyses were adjusted for co-medication and co-morbidity.
Results:
Among 192 893 incident topical corticosteroid users, 2212 developed diabetes and could be matched to 8582 controls. Current topical corticosteroid use was associated with an (unadjusted) 1.24-fold increased risk of diabetes (unadjusted OR 1.24; 95% CI 1.11, 1.40). The odds ratio increased to 1.32 with >180 days of topical corticosteroid use (95% CI 1.14, 1.54) and to 1.44 with a cumulative topical corticosteroid load (combined potency and amount) of 731–1460 mg (95% CI 1.21, 1.72). Among past/never users of systemic corticosteroids and/or inhaled corticosteroids, current use of topical corticosteroids remained associated with a 1.27-fold increased diabetes risk (unadjusted OR 1.27; 95% CI 1.10, 1.47) compared with past users of topical corticosteroids.
Conclusion:
An increased risk of new-onset diabetes may be an important consideration in the treatment of patients with topical corticosteroids, especially when intense skin treatment is needed. Future studies are needed to endorse these findings in other populations.