Prevalence and risk factors of diabetes in patients with Klinefelter syndrome: a longitudinal observational study

Key Laboratory of Endocrinology, Department of Endocrinology, Peking Union Medical College Hospital, Ministry of Health, Beijing, People's Republic of China.
Fertility and sterility (Impact Factor: 4.59). 08/2012; 98(5):1331-5. DOI: 10.1016/j.fertnstert.2012.07.1122
Source: PubMed


To evaluate the prevalence and risk factors of diabetes in patients with Klinefelter syndrome.
Retrospective longitudinal study.
Medical college hospital.
Klinefelter group (n = 39) and idiopathic hypogonadotropic hypogonadism (IHH) group (n = 40).
Testosterone replacement therapy.
The metabolic parameters, lipid profiles, and sex hormones were compared before and after T replacement therapy. The median duration of follow-up was 4 years in the Klinefelter group and 5.2 years in the IHH group.
The prevalence of diabetes was 20.5% (8 of 39) in the Klinefelter group and 5% in the IHH group. In the Klinefelter group, the incidence of diabetes was 12.5% in patients with 47,XXY karyotype and 57.1% in patients with other atypical karyotypes, such as 46XY/47XXY chimera. In the Klinefelter group, the average (±SD) age at diagnosis of diabetes was 27.1 ± 4.5 years. Four subjects had diabetes before T therapy, and their blood glucose did not improve after T replacement. One patient had a history of acute pancreatitis. Two other subjects had very high triglyceride levels. During the follow-up, body weight increased more in Klinefelter patients than in IHH patients.
The prevalence of diabetes is higher in Klinefelter patients than in IHH patients, possibly owing to abnormal karyotypes. Other risk factors, such as low T level, high body weight, acute pancreatitis, and high triglyceride levels, may also contribute to the development of diabetes.

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    • "Recently, a retrospective longitudinal study comparing KS patients with body mass index (BMI) and age-matched patients with idiopathic hypogonadotropic hypogonadism showed a significantly higher prevalence of diabetes among KS patients. Surprisingly, the prevalence increased markedly with testosterone treatment during a median follow up period of 4 years, but unfortunately, testosterone treatment only resulted in low to sub-normal testosterone levels in both groups and only crude measures of body composition changes were provided.66 "
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    ABSTRACT: Klinefelter syndrome (KS) (47, XXY) is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be diffi cult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These fi ndings should be a concern as they are not simply laboratory fi ndings; epidemiological studies in KS populations show an increased risk of both hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome.
    Asian Journal of Andrology 12/2013; DOI:10.4103/1008-682X.122201 · 2.60 Impact Factor
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    • "Currently, the treatment of KS often involves testosterone replacement therapy, which is understudied but reported to have positive effects on language, intellectual, and motor skills of pre-school KS boys [34,35]. Evidence suggests that in humans, not all KS phenotypes are the result of lower androgen levels [28,31,33]. Because direct sex chromosome effects are difficult to identify in patient populations or in previous animal models, they are poorly understood. "
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    ABSTRACT: Klinefelter syndrome (KS), caused by XXY karyotype, is characterized by low testosterone, infertility, cognitive deficits, and increased prevalence of health problems including obesity and diabetes. It has been difficult to separate direct genetic effects from hormonal effects in human studies or in mouse models of KS because low testosterone levels are confounded with sex chromosome complement. In this study, we present the Sex Chromosome Trisomy (SCT) mouse model that produces XXY, XYY, XY, and XX mice in the same litters, each genotype with either testes or ovaries. The independence of sex chromosome complement and gonadal type allows for improved recognition of sex chromosome effects that are not dependent on levels of gonadal hormones. All mice were gonadectomized and treated with testosterone for 3 weeks. Body weight, body composition, and motor function were measured. Before hormonal manipulation, XXY mice of both sexes had significantly greater body weight and relative fat mass compared to XY mice. After gonadectomy and testosterone replacement, XXY mice (both sexes) still had significantly greater body weight and relative fat mass, but less relative lean mass compared to XY mice. Liver, gonadal fat pad, and inguinal fat pad weights were also higher in XXY mice, independent of gonadal sex. In several of these measures, XX mice also differed from XY mice, and gonadal males and females differed significantly on almost every metabolic measure. The sex chromosome effects (except for testis size) were also seen in gonadally female mice before and after ovariectomy and testosterone treatment, indicating that they do not reflect group differences in levels of testicular secretions. XYY mice were similar to XY mice on body weight and metabolic variables but performed worse on motor tasks compared to other groups. We find that the new SCT mouse model for XXY and XYY recapitulates features found in humans with these aneuploidies. We illustrate that this model has significant promise for unveiling the role of genetic effects compared to hormonal effects in these syndromes, because many phenotypes are different in XXY vs. XY gonadal female mice which have never been exposed to testicular secretions.
    Biology of Sex Differences 08/2013; 4(1):15. DOI:10.1186/2042-6410-4-15 · 4.84 Impact Factor
  • BMJ (online) 12/2012; 345(dec03 1):e7558. DOI:10.1136/bmj.e7558 · 17.45 Impact Factor
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