Longitudinal changes in glucocorticoid metabolism are associated with later development of adverse metabolic phenotype
Abstract
OBJECTIVE: Dysregulation of enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistance; however, longitudinal changes in glucocorticoid metabolism have not been investigated. This study was performed to evaluate the role of glucocorticoid metabolism in the development of insulin resistance and obesity and to identify biomarkers for future development of metabolic disease. DESIGN: This was a prospective longitudinal observation study conducted over 5 years. METHODS: A 24-h collection was used to serially analyze urinary glucocorticoid and mineralocorticoid metabolites in 57 obese and overweight patients with no prior diagnosis of diabetes mellitus, recruited from the community. RESULTS: Baseline higher 5α-reductase (5αR) activity, but not 11β-hydroxysteroid dehydrogenase type 1 activity, was predictive of increased fasting insulin at final visit (11.4 compared with 7.4 mU/l in subjects with lower 5αR activity, P<0.05), area under the curve insulin response to oral glucose tolerance test (176.7 compared with 89.1 mU/l.h, P<0.01), and homeostasis model assessment (HOMA2-IR; 1.3 compared with 0.8, P<0.01). Higher total glucocorticoid production was associated with abnormal glucose tolerance and increased BMI. During this study, systolic blood pressure increased (equivalent to ∼1 mmHg/year), as did plasma sodium levels; this evidence of increased mineralocorticoid activity was associated with increased aldosterone metabolites and decreased 11β-hydroxysteroid dehydrogenase type 2 activity. CONCLUSIONS: Increased 5αR activity and glucocorticoid secretion rate over time are linked with the development of metabolic disease, and may represent targets for therapeutic intervention, which merits further study.
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Glucocorticoid metabolites are higher in men than in women and in obese than in lean persons.
“Glucocorticoid metabolites are higher in men than in women and in obese than in lean persons (345,346).”
From Adrenal incidentaloma (2020) · cites this paper as [345]
Adrenal steroid production and metabolism are affected by sex, age, and BMI.
“Adrenal steroid production and metabolism are affected by sex, age, and BMI (342,345,346).”
From Adrenal incidentaloma (2020) · cites this paper as [345]
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- Authors
- Crowley, R. K., Hughes, B., Gray, J., McCarthy, T., Hughes, S., Shackleton, C. H. L., Crabtree, N., Nightingale, P., Stewart, P. M., & Tomlinson, J. W.
- Affiliations
- Queen Elizabeth Hospital Birmingham (GB)
- Corresponding author
- Tomlinson, Jeremy W
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10
- Volume
- 171
- Issue
- 4
- Pages
- 433-442
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2069957802
- Cited by
- 26
- References
- 38
- Citations by year
- 2025: 2 · 2024: 2 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 3
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research (NF-SI-0508-10356)
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- glucocorticoid metabolism, 5α-reductase, 11β-hydroxysteroid dehydrogenase type 1, 11β-hydroxysteroid dehydrogenase type 2, mineralocorticoid activity, insulin resistance, obesity, glucose tolerance, longitudinal change, blood pressure, plasma sodium
- MeSH terms
- Adult, Aged, Blood Pressure, Female, Glucocorticoids, Humans, Insulin, Insulin Resistance, Longitudinal Studies, Male, Middle Aged, Mineralocorticoids, Phenotype, Predictive Value of Tests, Prospective Studies, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Linear Models, 11-beta-Hydroxysteroid Dehydrogenase Type 1
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