Exp Clin Endocrinol Diabetes 2007; 115 - P01_065
DOI: 10.1055/s-2007-972321

11beta-hydroxysteroid dehydrogenase type 1 in obese children

S Wiegand 1, A Richardt 1, T Remer 2, SA Wudy 3, JW Tomlinson 4, A Grüters 1, PM Stewart 4, CJ Strasburger 5, M Quinkler 5
  • 1Paediatric Endocrinology, Charité Campus Virchow, Berlin, Germany
  • 2Department of Nutrition and Health, Research Institute of Child Nutrition, Dortmund, Germany
  • 3Steroid Research Unit, Justus Liebig University, Gießen, Germany
  • 4Division of Medical Sciences, University of Birmingham, Birmingham, United Kingdom
  • 5Clinical Endocrinology, Charité, Campus Mitte, Berlin, Germany

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), which is predominantly expressed in liver and adipose tissue, regenerates active cortisol from inactive cortisone. Increased 11beta-HSD1 may cause tissue-specific Cushing syndrome with central obesity and impaired glucose homeostasis.

Design, patients and methods: Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male (aged 12–18) and 6 female (aged 12–18) obese pubertal children. In addition, analysis of 24h excretion rates of glucocorticoids were performed in obese and age- and sex-matched non-obese children using gas chromatographic-mass spectrometric (GC-MS) analysis.

Results: 11beta-HSD1 activity (urinary THF+5alphaTHF/THE ratio) was lower in obese compared to non-obese boys. In addition, obese children had a higher total cortisol metabolites excretion than non-obese children. 11beta-HSD1 activity was significantly related to age, but not to waist-to-hip ratio, fat mass (% of body mass), or insulin resistance index (HOMA). We did not find a gender difference regarding 11beta-HSD1 or 11beta-HSD2 (urinary free F/ free E ratio) activity. Standard deviation score (SDS)-BMI did not correlate with 11beta-HSD1 or -2 activity, or with total cortisol metabolites excretion. 11beta-HSD2 activity significantly correlated to abdominal circumference in obese children.

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 HPA axis.