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Diabetes Care 29:1591-1598, 2006
DOI: 10.2337/dc06-0145
© 2006 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Original Article

The Metabolic Syndrome Is Frequent in Klinefelter’s Syndrome and Is Associated With Abdominal Obesity and Hypogonadism

Anders Bojesen, MD, PHD1,2, Kurt Kristensen, MD, PHD3, Niels H. Birkebaek, MD, PHD3, Jens Fedder, MD, PHD4, Leif Mosekilde, MD, DMSCI5, Paul Bennett, MD6, Peter Laurberg, MD, DMSCI7, Jan Frystyk, MD, DMSCI1, Allan Flyvbjerg, MD, DMSCI1, Jens S. Christiansen, MD, DMSCI1 and Claus H. Gravholt, MD, DMSCI1

1 Medical Department M, Endocrinology and Diabetes, and Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Aarhus, Denmark
2 Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark
3 Department of Pediatrics, Aarhus University Hospital, Skejby Hospital, Aarhus, Denmark
4 Fertility Clinic and Scientific Unit, Braedstrup Hospital, Braedstrup, Denmark
5 Medical Department C, Aarhus University Hospital, Aarhus, Denmark
6 Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark
7 Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

Address correspondence and reprint requests to Anders Bojesen, MD, Medical Department M, Endocrinology and Diabetes, Aarhus University Hospital, Noerrebrogade 42-44, DK-8000, Aarhus C, Denmark. E-mail: anders.bojesen{at}dadlnet.dk

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.

Abbreviations: ATPIII, Adult Treatment Panel III • BFtr, truncal fat • CRP, C-reactive protein • DEXA, dual-energy X-ray absorptiometry • FPG, fasting plasma glucose • FSH, follicle-stimulating hormone • HOMA, homeostasis model assessment • HOMA2%S, HOMA of insulin sensitivity • IMAT, intermuscular adipose tissue • LBM, lean body mass • LH, luteinizing hormone • NCEP, National Cholesterol Education Program • SHBG, sex hormone–binding globulin • SMM, skeletal muscle mass • TBF, total body fat


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This article has been cited by other articles:


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 Mol Hum ReprodHome page
A.M. Ottesen, I.D. Garn, L. Aksglaede, A. Juul, and E. Rajpert-De Meyts
A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene
Mol. Hum. Reprod., October 1, 2007; 13(10): 745 - 750.
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