Effects of topical corticosteroid vs. 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

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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 two weeks followed by twice weekly application for four 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 two weeks of daily treatment and after further four weeks of twice-weekly maintenance treatment.

RESULTS: AD severity improved with both treatments and systemic inflammation was reduced. After two 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 two and six 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.

OriginalsprogEngelsk
TidsskriftAllergy
Vol/bind78
Udgave nummer7
Sider (fra-til)1964-1979
Antal sider16
ISSN0105-4538
DOI
StatusUdgivet - 2023

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