title: Long-term glucocorticoid concentrations as a risk factor for childhood obesity and adverse body-fat distribution.
abstract: Childhood obesity is an important risk factor for premature development of the metabolic syndrome (MetS) at adulthood. There is need for understanding of the mechanisms underlying the MetS and obesity. Patients with Cushing's disease suffer from similar metabolic complications, leading to the hypothesis that inter-individual cortisol variation may contribute to the onset of obesity. In addition, glucocorticoid receptor (GR)-gene polymorphisms resulting in differential glucocorticoid (GC) sensitivity, have been associated with an adverse metabolic profile.
  
  
  
  To study associations of GC levels in scalp hair, as a marker of long-term systemic GC concentrations, and genetically determined GC sensitivity with obesity and body-fat distribution in children.
  
  
  
  We performed a cross-sectional study of cortisol and cortisone concentrations over a 3-month period, measured by LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in hair of 3019 6-year-old children participating in the Generation R study. Genotyping of GR-gene polymorphisms was performed.
  
  
  
  Of all children, 4.3% was obese and 13.4% overweight. Cortisol was significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3-26.9)) and overweight (OR: 1.4 (1.0-2.0)). Cortisone was associated with risk of obesity (OR: 1.9 (1.0-3.5)). Cortisol and cortisone were significantly positively associated with body mass index, fat mass (FM) index and android/gynecoid FM ratio. GR polymorphisms were not associated with adiposity parameters.
  
  
  
  Long-term cortisol concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.|Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.|The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Noppe
authors.affiliation: Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.|Department of Pediatrics, Sophia Children's Hospital, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: E L T
authors.initials: EL
authors.lastname: van den Akker
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.|Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.|Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Y B
authors.initials: YB
authors.lastname: de Rijke
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.|Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Koper
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.|Department of Pediatrics, Sophia Children's Hospital, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.|Department of Epidemiology and Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: V W
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.|Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: E F C
authors.initials: EF
authors.lastname: van Rossum
mesh_terms: D017668:Age of Onset; D015415:Biomarkers / Q000378:metabolism; D050218:Body Fat Distribution; D002648:Child; D003348:Cortisone / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000378:metabolism*; D006197:Hair / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000378:metabolism* / Q000517:prevention & control; D009426:Netherlands / Q000453:epidemiology; D063766:Pediatric Obesity / Q000453:epidemiology / Q000378:metabolism* / Q000517:prevention & control; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D003348:Cortisone; D006854:Hydrocortisone