Increased central adiposity and decreased subcutaneous adipose tissue 11β-hydroxysteroid dehydrogenase type 1 are associated with deterioration in glucose tolerance-a longitudinal cohort study
Author(s)
Type
Journal Article
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.
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.
Date Issued
2019-07-01
Date Acceptance
2019-01-16
Citation
Clinical Endocrinology, 2019, 91 (1), pp.72-81
ISSN
0300-0664
Publisher
Wiley
Start Page
72
End Page
81
Journal / Book Title
Clinical Endocrinology
Volume
91
Issue
1
Copyright Statement
© 2019 John Wiley & Sons Ltd
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30667079
Subjects
11 beta-HSD1
11-BETA-HSD1
cortisol
CORTISONE
CUSHINGS-DISEASE
Endocrinology & Metabolism
gene expression
GENE-EXPRESSION
GLUCOCORTICOID METABOLISM
glucose tolerance
INSULIN-RESISTANCE
Life Sciences & Biomedicine
MARKERS
metabolic function
OBESE-PATIENTS
OVERWEIGHT
Science & Technology
subcutaneous adipose tissue
WEIGHT-LOSS
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2019-01-22