Effects of topical corticosteroid versus tacrolimus on insulin sensitivity and bone homeostasis in adults with atopic dermatitis—A randomized controlled study

• Published in: Allergy (Copenhagen) Vol. 78; no. 7; pp. 1964 - 1979
• Main Authors: Gether, Lise, Storgaard, Heidi, Kezic, Sanja, Jakasa, Ivone, Hartmann, Bolette, Skov‐Jeppesen, Kirsa, Holst, Jens J., Pedersen, Anders J., Forman, Julie, Hall, Gerrit, Sørensen, Ole E., Skov, Lone, Røpke, Mads A., Knop, Filip K., Thyssen, Jacob Pontoppidan
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.07.2023
• Subjects: Adrenal Cortex Hormones - adverse effects; Adult; Atopic dermatitis; Betamethasone; Biomarkers; Bone growth; Bone resorption; Bone turnover; calcineurin inhibitor; Collagen; corticosteroid; Corticosteroids; Dermatitis; Dermatitis, Atopic - chemically induced; Dermatitis, Atopic - drug therapy; Dermatologic Agents; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Double-Blind Method; Eczema; Epidemiology; Glucocorticoids; Glucose metabolism; Homeostasis; Humans; Inflammation; Insulin Resistance; Osteogenesis; Osteoporosis; Steroids; Tacrolimus; Tacrolimus - adverse effects; Treatment Outcome; type 2 diabetes; corticosteroid; atopic dermatitis; type 2 diabetes; calcineurin inhibitor; osteoporosis
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.15690

Introduction Topical corticosteroids (TCS), used to treat atopic dermatitis (AD), have been associated with type 2 diabetes and osteoporosis in epidemiological studies, possibly explained by systemic absorption. Objectives We examined whether intensive daily whole‐body TCS treatment over 2 weeks followed by twice weekly application for 4 weeks could elicit insulin resistance and increase bone resorption in adults with AD. Methods A randomized parallel‐group double‐blind double‐dummy non‐corticosteroid‐based active comparator study design was completed in Copenhagen, Denmark. Thirty‐six non‐obese, non‐diabetic adults with moderate‐to‐severe AD were randomized to whole‐body treatment with betamethasone 17‐valerate 0.1% plus a vehicle once daily or tacrolimus 0.1% twice daily after washout. Insulin sensitivity assessed by the hyperinsulinemic‐euglycemic clamp combined with tracer infusions and biomarkers of bone formation (P1NP) and resorption (CTX) were evaluated at baseline, after 2 weeks of daily treatment and after further 4 weeks of twice‐weekly maintenance treatment. Results AD severity improved with both treatments and systemic inflammation was reduced. After 2 weeks, we observed similar increase in peripheral insulin sensitivity with use of betamethasone (n = 18) and tacrolimus (n = 18). Bone resorption biomarker, CTX, was unchanged, while bone formation marker, P1NP, decreased after betamethasone treatment after both 2 and 6 weeks but remained unchanged in the tacrolimus arm. Conclusions Whole‐body treatment with TCS leads to systemic exposure but appears not to compromise glucose metabolism during short‐term use, which may be a result of reduced systemic inflammatory activity. The negative impact on bone formation could be regarded an adverse effect of TCS. This study examined whether intensive daily whole‐body TCS treatment over 2 weeks followed by twice weekly application for 4 weeks could elicit insulin resistance and increase bone resorption in adults with AD. Insulin sensitivity increased 12.6% after 2 weeks of betamethasone and 6.40% after 6 weeks. A slight increase in insulin sensitivity was found after 2 weeks of tacrolimus treatment. P1NP decreased significantly with 10.7% in the betamethasone group after 2 weeks. AD severity improved with both treatments and systemic inflammation was reduced. Abbreviations: AD, atopic dermatitis; P1NP, N‐terminal propeptide of type I procollagen; Rd, rate of glucose disappearance; TCS, topical corticosteroids