Journal Article


Increased central adiposity and decreased subcutaneous adipose tissue 11β-hydroxysteroid dehydrogenase type 1 are associated with deterioration in glucose tolerance-A longitudinal cohort study

Abstract

Objective and Context. Increasing adiposity, ageing and tissue‐specific regeneration of cortisol through the activity of 11β‐hydroxysteroid dehydrogenase type 1 have been associated with deterioration in glucose tolerance. We undertook a longitudinal, prospective clinical study to determine if alterations in local glucocorticoid metabolism track with changes in glucose tolerance. Design, Patients, and Measurements. Sixty‐five overweight/obese individuals (mean age 50.3 ± 7.3 years) underwent oral glucose tolerance testing, body composition assessment, subcutaneous adipose tissue biopsy and urinary steroid metabolite analysis annually for up to 5 years. Participants were categorized into those in whom glucose tolerance deteriorated (“deteriorators”) or improved (“improvers”). Results. Deteriorating glucose tolerance was associated with increasing total and trunk fat mass and increased subcutaneous adipose tissue expression of lipogenic genes. Subcutaneous adipose tissue 11β‐HSD1 gene expression decreased in deteriorators, and at study completion, it was highest in the improvers. There was a significant negative correlation between change in area under the curve glucose and 11β‐HSD1 expression. Global 11β‐HSD1 activity did not change and was not different between deteriorators and improvers at baseline or follow‐up. Conclusion. Longitudinal deterioration in metabolic phenotype is not associated with increased 11β‐HSD1 activity, but decreased subcutaneous adipose tissue gene expression. These changes may represent a compensatory mechanism to decrease local glucocorticoid exposure in the face of an adverse metabolic phenotype.

Attached files

Authors

Crowley, Rachel K.
Woods, Conor P.
Hughes, Beverly A.
Gray, Joanna
McCarthy,Theresa
Taylor, Angela E.
Gathercole, Laura L.
Shackleton, Cedric H.L.
Crabtree, Nicola
Arlt, Wiebke
Stewart, Paul M.
Tomlinson, Jeremy W.

Oxford Brookes departments

Department of Biological and Medical Sciences

Dates

Year of publication: 2019
Date of RADAR deposit: 2023-02-24



© Wiley. “For non-commercial and non-promotional research and private study purposes, individual users may view, print, download and copy self-archived articles, as well as text and data mine the content.” Further details: https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html


Related resources

This RADAR resource is the Accepted Manuscript of Increased central adiposity and decreased subcutaneous adipose tissue 11β-hydroxysteroid dehydrogenase type 1 are associated with deterioration in glucose tolerance-A longitudinal cohort study

Details

  • Owner: Joseph Ripp
  • Collection: Outputs
  • Version: 1 (show all)
  • Status: Live
  • Views (since Sept 2022): 369