Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys.
OBJECTIVE: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing's syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1) regenerates active cortisol...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
2007
|
_version_ | 1797061360589209600 |
---|---|
author | Wiegand, S Richardt, A Remer, T Wudy, SA Tomlinson, J Hughes, B Grüters, A Stewart, P Strasburger, C Quinkler, M |
author_facet | Wiegand, S Richardt, A Remer, T Wudy, SA Tomlinson, J Hughes, B Grüters, A Stewart, P Strasburger, C Quinkler, M |
author_sort | Wiegand, S |
collection | OXFORD |
description | OBJECTIVE: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing's syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1) regenerates active cortisol from inactive cortisone. Altered 11beta-HSD1 may cause tissue-specific Cushing's syndrome with central obesity and impaired glucose homeostasis. DESIGN, PATIENTS, AND METHODS: Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male and 6 female obese pubertal children (aged 12-18 years, Tanner stages 2-5). In addition, analyses of 24-h excretion rates of glucocorticoids were also performed in 21 age-, sex-, and pubertal stage-matched non-obese children using gas chromatographic-mass spectrometric (GC-MS) analysis. RESULTS: 11beta-HSD1 activity (urinary tetrahydrocortisol (THF) + 5alpha-THF/tetrahydrocortisone (THE) ratio) was lower in obese when compared with non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11beta-HSD1 activity was significantly related to age in lean and obese children. Standard deviation score (SDS)-body mass index did not correlate with 11beta-HSD1 activity, or with total cortisol metabolite excretion within each group. In obese children, 11beta-HSD1 activity and total cortisol metabolite excretion showed no correlation to waist-to-hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index. CONCLUSIONS: In conclusion, our findings strongly suggest that 11beta-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children have a higher total cortisol metabolites excretion suggesting a stimulated hypothalamus-pituitary-adrenal axis. |
first_indexed | 2024-03-06T20:30:00Z |
format | Journal article |
id | oxford-uuid:30b81138-450e-4a5a-9ea5-496e068025ce |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T20:30:00Z |
publishDate | 2007 |
record_format | dspace |
spelling | oxford-uuid:30b81138-450e-4a5a-9ea5-496e068025ce2022-03-26T13:03:16ZReduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:30b81138-450e-4a5a-9ea5-496e068025ceEnglishSymplectic Elements at Oxford2007Wiegand, SRichardt, ARemer, TWudy, SATomlinson, JHughes, BGrüters, AStewart, PStrasburger, CQuinkler, M OBJECTIVE: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing's syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1) regenerates active cortisol from inactive cortisone. Altered 11beta-HSD1 may cause tissue-specific Cushing's syndrome with central obesity and impaired glucose homeostasis. DESIGN, PATIENTS, AND METHODS: Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male and 6 female obese pubertal children (aged 12-18 years, Tanner stages 2-5). In addition, analyses of 24-h excretion rates of glucocorticoids were also performed in 21 age-, sex-, and pubertal stage-matched non-obese children using gas chromatographic-mass spectrometric (GC-MS) analysis. RESULTS: 11beta-HSD1 activity (urinary tetrahydrocortisol (THF) + 5alpha-THF/tetrahydrocortisone (THE) ratio) was lower in obese when compared with non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11beta-HSD1 activity was significantly related to age in lean and obese children. Standard deviation score (SDS)-body mass index did not correlate with 11beta-HSD1 activity, or with total cortisol metabolite excretion within each group. In obese children, 11beta-HSD1 activity and total cortisol metabolite excretion showed no correlation to waist-to-hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index. CONCLUSIONS: In conclusion, our findings strongly suggest that 11beta-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children have a higher total cortisol metabolites excretion suggesting a stimulated hypothalamus-pituitary-adrenal axis. |
spellingShingle | Wiegand, S Richardt, A Remer, T Wudy, SA Tomlinson, J Hughes, B Grüters, A Stewart, P Strasburger, C Quinkler, M Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys. |
title | Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys. |
title_full | Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys. |
title_fullStr | Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys. |
title_full_unstemmed | Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys. |
title_short | Reduced 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys. |
title_sort | reduced 11beta hydroxysteroid dehydrogenase type 1 activity in obese boys |
work_keys_str_mv | AT wiegands reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys AT richardta reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys AT remert reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys AT wudysa reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys AT tomlinsonj reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys AT hughesb reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys AT grutersa reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys AT stewartp reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys AT strasburgerc reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys AT quinklerm reduced11betahydroxysteroiddehydrogenasetype1activityinobeseboys |