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

Lise Gether, Heidi Storgaard, Sanja Kezic, Ivone Jakasa, Bolette Hartmann, Kirsa Skov-Jeppesen, Jens J Holst, Anders J Pedersen, Julie Forman, Gerrit van Hall, Ole E Sørensen, Lone Skov, Mads A Røpke, Filip K Knop*, Jacob P Thyssen*

*Corresponding author for this work

Abstract

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.

Original languageEnglish
JournalAllergy
Volume78
Issue number7
Pages (from-to)1964-1979
Number of pages16
ISSN0105-4538
DOIs
Publication statusPublished - Jul 2023

Keywords

  • Adrenal Cortex Hormones/adverse effects
  • Adult
  • Betamethasone
  • Dermatitis, Atopic/drug therapy
  • Dermatologic Agents
  • Diabetes Mellitus, Type 2
  • Double-Blind Method
  • Glucocorticoids
  • Homeostasis
  • Humans
  • Insulin Resistance
  • Tacrolimus/adverse effects
  • Treatment Outcome

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