title: The metabolic syndrome is frequent in Klinefelter's syndrome and is associated with abdominal obesity and hypogonadism.
abstract: OBJECTIVE
  Klinefelter's syndrome is associated with an increased prevalence of diabetes, but the pathogenesis is unknown. Accordingly, the aim of this study was to investigate measures of insulin sensitivity, the metabolic syndrome, and sex hormones in patients with Klinefelter's syndrome and an age-matched control group. RESEARCH DESIGN AN METHODS: In a cross-sectional study, we examined 71 patients with Klinefelter's syndrome, of whom 35 received testosterone treatment, and 71 control subjects. Body composition was evaluated using dual-energy X-ray absorptiometry scans. Fasting blood samples were analyzed for sex hormones, plasma glucose, insulin, C-reactive protein (CRP), and adipocytokines. We analyzed differences between patients with untreated Klinefelter's syndrome and control subjects and subsequently analyzed differences between testosterone-treated and untreated Klinefelter's syndrome patients.
  
  
  RESULTS
  Of the patients with Klinefelter's syndrome, 44% had metabolic syndrome (according to National Cholesterol Education Program/Adult Treatment Panel III criteria) compared with 10% of control subjects. Insulin sensitivity (assessed by homeostasis model assessment 2 modeling), androgen, and HDL cholesterol levels were significantly decreased, whereas total fat mass and LDL cholesterol, triglyceride, CRP, leptin, and fructosamine levels were significantly increased in untreated Klinefelter's syndrome patients. In treated Klinefelter's syndrome patients, LDL cholesterol and adiponectin were significantly decreased, whereas no difference in body composition was found in comparison with untreated Klinefelter's syndrome patients. Multivariate analyses showed that truncal fat was the major determinant of metabolic syndrome and insulin sensitivity.
  
  
  CONCLUSIONS
  The prevalence of metabolic syndrome was greatly increased, whereas insulin sensitivity was decreased in Klinefelter's syndrome. Both correlated with truncal obesity. Hypogonadism in Klinefelter's syndrome may cause an unfavorable change in body composition, primarily through increased truncal fat and decreased muscle mass. Testosterone treatment in Klinefelter's syndrome only partly corrected the unfavorable changes observed in untreated Klinefelter's syndrome, perhaps due to insufficient testosterone doses.
authors.affiliation: Medical Department M, Endocrinology and Diabetes, Aarhus University Hospital, Noerrebrogade 42-44, DK-8000, Aarhus C, Denmark. anders.bojesen@dadlnet.dk
authors.forename: Anders
authors.initials: A
authors.lastname: Bojesen
authors.forename: Kurt
authors.initials: K
authors.lastname: Kristensen
authors.forename: Niels H
authors.initials: NH
authors.lastname: Birkebaek
authors.forename: Jens
authors.initials: J
authors.lastname: Fedder
authors.forename: Leif
authors.initials: L
authors.lastname: Mosekilde
authors.forename: Paul
authors.initials: P
authors.lastname: Bennett
authors.forename: Peter
authors.initials: P
authors.lastname: Laurberg
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Claus H
authors.initials: CH
authors.lastname: Gravholt
mesh_terms: D050153:Abdominal Fat / Q000033:anatomy & histology*; D000328:Adult; D000368:Aged; D000886:Anthropometry; D001823:Body Composition; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000150:complications*; D007713:Klinefelter Syndrome / Q000150:complications* / Q000188:drug therapy; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology*; D008875:Middle Aged; D015999:Multivariate Analysis; D012044:Regression Analysis; D013739:Testosterone / Q000627:therapeutic use
chemical_list: D012739:Gonadal Steroid Hormones; D013739:Testosterone