Background and Aim: Klinefelter syndrome (47,XXY; KS) is a very common chromosomal disorder, affecting 1:600 men. Klinefelter men have been described to exhibit clinically relevant metabolic patterns related to a pro-inflammatory status, resulting in a high prevalence of insulin resistance and cardiovascular impairment. Testosterone deficiency in form of primary hypogonadism is a common feature in these men.
EXAKT (epigenetics, X-chromosomal features and clinical applications in Klinefelter syndrome trial) is a Muenster-based prospective project involving Klinefelter patients (n=130), and their parents assessing a wide area of cardiovascular, inflammatory and metabolic factors as well as sex steroids and questionnaires in comparison to age-matched healthy male and female controls (2×n=50). A broad range of genetic and epigenetic investigations completes the approach.
Here, we present first and novel clinical data comparing Klinefelter patients to healthy male controls with regard to cardiovascular and metabolic parameters.
Results: KS patients had a higher waist circumference and Body Mass Index in comparison to controls. Further on, decreased insulin sensitivity, higher levels of triglycerides and lipoprotein type a as well as lower concentrations of HDL-cholesterol were found in patients. Levels of high-resolution C-reactive protein were elevated in Klinefelter patients. Consequently, the prevalence of the metabolic syndrome according the Harmonized Criteria was markedly higher in Klinefelter men than in controls (52/130 vs 5/50). Corroboratingly, carotid artery intima-media thickness was increased and flow mediated dilatation of the brachial artery was decreased in patients vs controls. These differences were statistically significant. Metabolic disadvantages of patients were further enhanced by low testosterone concentrations and already present in the sub-cohort younger than 40 years.
Conclusion: The EXAKT project revealed an unfavorable pattern of cardiovascular risk factors in KS in comparison to healthy male controls. This picture is already present in younger patients and enforced by testosterone deficiency.
Supported by the IZKF Münster: CRA03/09; and DFG (grant no. WI2723/4-1).
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
05 - 09 May 2012
European Society of Endocrinology