nach oben

Current Diabetes Reports

Erschienen in:

01.09.2019 | Other Forms of Diabetes and Its Complications (JJ Nolan and H Thabit, Section Editors)

Klinefelter Syndrome and Diabetes

verfasst von: Mark J. O’Connor, Emma A. Snyder, Frances J. Hayes

Erschienen in: Current Diabetes Reports | Ausgabe 9/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

Klinefelter syndrome (KS) is associated with increased insulin resistance and high rates of type 2 diabetes (T2DM). Our aim was to review what is known about the prevalence of diabetes in men with KS, potential mechanisms underlying the observed metabolic phenotype, and the data that are available to guide treatment decisions.

Recent Findings

The increased prevalence of T2DM seen in men with KS appears to be the result of multiple mechanisms including increased truncal adiposity and socioeconomic disadvantages, but it is likely not a direct consequence of hypogonadism alone. No randomized trials have been conducted to evaluate the impact of testosterone replacement therapy on T2DM in men with KS, but observational data suggest that testosterone replacement is not associated with lower rates of diabetes or improved glycemic control.

Summary

Metabolic derangements are common in KS, but treatment strategies specific to this population are lacking. Early lifestyle and dietary interventions are likely important. Additional research is needed to dissect the complex interaction between genotype and metabolic phenotype. Collaboration between academic centers caring for men with KS is needed to facilitate the development of evidence-based clinical practice guidelines, which would inform optimal screening and treatment strategies for this patient population.

Klinefelter HF, Reifenstein EC, Albright F. Syndrome characterized by gynecomastia, aspermatogenesis without A-leydigism, and increased excretion of follicle-stimulating hormone. J Clin Endocrinol. 1942;2:615–27. https://doi.org/10.1210/jcem-2-11-615.CrossRef

Bradbury JT, Bunge RG, Boccabella RA. Chromatin test in Klinefelter’s syndrome. J Clin Endocrinol Metab. 1956;16:689–90. https://doi.org/10.1210/jcem-16-5-689.CrossRefPubMed

Plunkett ER, Barr ML. Testicular dysgenesis affecting the seminiferous tubules principally, with chromatin-positive nuclei. Lancet. 1956;271:2853–4.

Barr ML. The natural history of Klinefelter’s syndrome. Fertil Steril. 1966;17:429–41.CrossRef

Jacobs PA, Strong JA. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature. 1959;183:302–3.CrossRef

Groth KA, Skakkebaek A, Høst C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome—a clinical update. J Clin Endocrinol Metab. 2013;98:20–30. https://doi.org/10.1210/jc.2012-2382.CrossRefPubMed

Morris JK, Alberman E, Scott C, Jacobs P. Is the prevalence of Klinefelter syndrome increasing? Eur J Hum Genet. 2008;16:163–70. https://doi.org/10.1038/sj.ejhg.5201956.CrossRefPubMed

Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab. 2003;88:622–6. https://doi.org/10.1210/jc.2002-021491.CrossRefPubMed

Achermann JC, Hughes IA. Pediatric disorders of sex development. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, editors. Williams Textbook of Endocrinology. 13th edon ed. Amsterdam: Elsevier; 2017.

10.

Ottesen AM, Aksglaede L, Garn I, Tartaglia N, Tassone F, Gravholt CH, et al. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy. Am J Med Genet Part A. 2010;152A:1206–12. https://doi.org/10.1002/ajmg.a.33334.CrossRefPubMed

11.

•• Gravholt CH, Chang S, Wallentin M, Fedder J, Moore P, Skakkebaek A. Klinefelter syndrome: integrating genetics, neuropsychology, and endocrinology. Endocr Rev. 2018;39:389–423. https://doi.org/10.1210/er.2017-00212 This review article provides a comprehensive update on research and clinical best practices in treating individuals with Klinefelter syndrome, emphasizing a multidisciplinary approach. CrossRefPubMed

12.

Belling K, Russo F, Jensen AB, Dalgaard MD, Westergaard D, Rajpert-De Meyts E, et al. Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity. Hum Mol Genet. 2017;26:1219–29. https://doi.org/10.1093/hmg/ddx014.CrossRefPubMedPubMedCentral

13.

Bojesen A, Juul S, Birkebaek N, Gravholt CH. Increased mortality in Klinefelter syndrome. J Clin Endocrinol Metab. 2004;89:3830–4. https://doi.org/10.1210/jc.2004-0777.CrossRefPubMed

14.

Swerdlow AJ, Higgins CD, Schoemaker MJ, Wright AF, Jacobs PA. Mortality in patients with Klinefelter syndrome in Britain: a cohort study. J Clin Endocrinol Metab. 2005;90:6516–22. https://doi.org/10.1210/jc.2005-1077.CrossRefPubMed

15.

Nielsen J, Johansen K, Yde H. Frequency of diabetes mellitus in patients with Klinefelter’s syndrome of different chromosome constitutions and the XYY syndrome. Plasma insulin and growth hormone level after a glucose load. J Clin Endocrinol Metab. 1969;29:1062–73. https://doi.org/10.1210/jcem-29-8-1062.CrossRefPubMed

16.

Han SJ, Kim KS, Kim W, Kim JH, Lee YH, Nam JS, et al. Obesity and hyperglycemia in Korean men with Klinefelter syndrome: The Korean Endocrine Society Registry. Endocrinol Metab (Seoul). 2016;31:598–603. https://doi.org/10.3803/EnM.2016.31.4.598.CrossRef

17.

Bojesen A, Juul S, Birkebaek NH, Gravholt CH. Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. J Clin Endocrinol Metab. 2006;91:1254–60. https://doi.org/10.1210/jc.2005-0697.CrossRefPubMed

18.

Salzano A, D’Assante R, Heaney LM, Monaco F, Rengo G, Valente P, et al. Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives. Endocrine. 2018;61:194–203. https://doi.org/10.1007/s12020-018-1584-6.CrossRefPubMed

19.

Panimolle F, Tiberti C, Granato S, Semeraro A, Gianfrilli D, Anzuini A, et al. Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter’s syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men. Endocrine. 2016;52:157–64. https://doi.org/10.1007/s12020-015-0613-y.CrossRefPubMed

20.

World Health Organization Global report on diabetes. World Health Organization 2016:1–87. http://www.who.int/iris/handle/10665/204871. Accessed 24 May 2019.

21.

Brand JS, van der Tweel I, Grobbee DE, Emmelot-Vonk MH, van der Schouw YT. Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies. Int J Epidemiol. 2011;40:189–207. https://doi.org/10.1093/ije/dyq158.CrossRefPubMed

22.

Basaria S, Muller DC, Carducci MA, Egan J, Dobs AS. Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy. Cancer. 2006;106:581–8. https://doi.org/10.1002/cncr.21642.CrossRefPubMed

23.

Keating NL, O’Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006;24:44448–56. https://doi.org/10.1200/JCO.2006.06.2497.CrossRef

24.

Lin HY, Xu Q, Yeh S, Wang RS, Sparks JD, Chang C. Insulin and leptin resistance with hyperleptinemia in mice lacking androgen receptor. Diabetes. 2005;54:1717–25. https://doi.org/10.2337/diabetes.54.6.1717.CrossRefPubMed

25.

Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi D, et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab. 2005;90:2636–41. https://doi.org/10.1210/jc.2004-2190.CrossRefPubMed

26.

Bojesen A, Kristensen K, Birkebaek NH, Fedder J, Mosekilde L, Bennett P, et al. The metabolic syndrome is frequent in Klinefelter’s syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care. 2006;29:1591–8. https://doi.org/10.2337/dc06-0145.CrossRefPubMed

27.

Bardsley MZ, Falkner B, Kowal K, Ross JL. Insulin resistance and metabolic syndrome in prepubertal boys with Klinefelter syndrome. Acta Paediatr. 2011;100:866–70. https://doi.org/10.1111/j.1651-2227.2011.02161.x.CrossRefPubMedPubMedCentral

28.

Davis S, Lahlou N, Bardsley M, Temple MC, Kowal K, Pyle L, et al. Gonadal function is associated with cardiometabolic health in pre-pubertal boys with Klinefelter syndrome. Andrology. 2016;4:1169–77. https://doi.org/10.1111/andr.12275.CrossRefPubMedPubMedCentral

29.

Rotondi M, Coperchini F, Renzullo A, Accardo G, Esposito D, Groppelli G, et al. High circulating levels of CCL2 in patients with Klinefelter’s syndrome. Clin Endocrinol. 2014;80:465–7. https://doi.org/10.1111/cen.12245.CrossRef

30.

Jiang-Feng M, Hong-Li X, Xue-Yan W, Min N, Shuang-Yu L, Hong-Ding X, et al. Prevalence and risk factors of diabetes in patients with Klinefelter syndrome: a longitudinal observational study. Fertil Steril. 2012;98:1331–5. https://doi.org/10.1016/j.fertnstert.2012.07.1122.CrossRefPubMed

31.

Chang S, Skakkebaek A, Trolle C, Bojesen A, Hertz JM, Cohen A, et al. Anthropometry in Klinefelter syndrome—multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism. J Clin Endocrinol Metab. 2015;100:E508–17. https://doi.org/10.1210/jc.2014-2834.CrossRefPubMed

32.

Bojesen A, Hertz JM, Gravholt CH. Genotype and phenotype in Klinefelter syndrome – impact of androgen receptor polymorphism and skewed X inactivation. Int J Androl. 2011;34:e642–8. https://doi.org/10.1111/j.1365-2605.2011.01223.x.CrossRefPubMed

33.

Bojesen A, Stochholm K, Juul S, Gravholt CH. Socioeconomic trajectories affect mortality in Klinefelter syndrome. J Clin Endocrinol Metab. 2011;96:2098–104. https://doi.org/10.1210/jc.2011-0367.CrossRefPubMed

34.

Corona G, Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, et al. Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl. 2011;34:528–40. https://doi.org/10.1111/j.1365-2605.2010.01117.x.CrossRefPubMed

35.

Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006;154:899–906. https://doi.org/10.1530/eje.1.02166.CrossRefPubMed

36.

Groti K, Žuran I, Antonic B, Forsnaric L, Pfeifer M. The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes. Aging Male. 2018;21:158–69. https://doi.org/10.1080/13685538.2018.1468429.CrossRefPubMed

37.

Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 Study). Diabetes Care. 2011;34:828–37. https://doi.org/10.2337/dc10-1233.CrossRefPubMedPubMedCentral

38.

Tan WS, Low WY, Ng CJ, Tan WK, Tong SF, Ho C, et al. Efficacy and safety of long-acting intramuscular testosterone undecanoate in aging men: a randomised controlled study. BJU Int. 2013;111:1130–40. https://doi.org/10.1111/bj.12037.CrossRefPubMed

39.

Mohler ER, Ellenberg SS, Lewis CE, Wenger NK, Budoff MJ, Lewis MR, et al. The Effect of testosterone on cardiovascular biomarkers in the testosterone trials. J Clin Endocrinol Metab. 2018;103:681–8. https://doi.org/10.1210/jc.2017-02243.CrossRefPubMed

40.

Gianatti EJ, Dupuis P, Hoermann R, Strauss BJ, Wentworth JM, Zajac JD, et al. Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes: a randomized controlled trial. Diabetes Care. 2014;37:2098–107. https://doi.org/10.2337/dc13-2845.CrossRefPubMed

41.

• Grossmann M, Hoermann R, Wittert G, Yeap BB. Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Clin Endocrinol. 2015;83:344–51. https://doi.org/10.1111/cen.12664 This recent meta-analysis of trials studying the effectiveness of testosterone treatment in men with T2DM, not specific to men with KS, suggests that the data do not support the routine use of testosterone to treat T2DM. CrossRef

42.

• Davis SM, Cox-Martin MG, Bardsley MZ, Kowal K, Zeitler PS, Ross JL. Effects of oxandrolone on cardiometabolic health in boys with Klinefelter syndrome: a randomized controlled trial. J Clin Endocrinol Metab. 2017;102:176–84. https://doi.org/10.1210/jc.2016-2904 Androgen replacement in prepubertal boys with KS did not show a beneficial effect on metrics of diabetes such as fasting glucose levels or HbA1c. CrossRefPubMed

43.

Pasquali D, Arcopinto M, Renzullo A, Rotondi M, Accardo G, Salzano A, et al. Cardiovascular abnormalities in Klinefelter syndrome. Int J Cardiol. 2013;168:754–9. https://doi.org/10.1016/j.ijcard.2012.09.215.CrossRefPubMed

44.

Kaukua J, Pekkarinen T, Sane T, Mustajoki P. sex hormones and sexual function in obese men losing weight. Obes Res. 2003;11:689–94. https://doi.org/10.1038/oby.2003.98.CrossRefPubMed

45.

Nisakanen L, Kaaksonen DE, Punnonen K, Mustajoki P, Kaukua J, Rissanen A. Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab. 2004;6:208–15. https://doi.org/10.1111/j.1462-8902.2004.00335.x.CrossRef

46.

Globerman H, Shen-Orr Z, Karnieli E, Aloni Y, Charuzi I. Inhibin B in men with severe obesity and after weight reduction following gastroplasty. Endocr Res. 2005;31:17–26.CrossRef

47.

Khoo J, Dhamodaran S, Chen DD, Yap SY, Chen RY, Tian RH. Exercise-induced weight loss is more effective than dieting for improving adipokine profile, insulin resistance, and inflammation in obese men. Int J Sport Nutr Exerc Metab. 2015 Dec;25(6):566–75. https://doi.org/10.1123/ijsnem.2015-0025.CrossRefPubMed

48.

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393–403. https://doi.org/10.1056/NEJMoa012512.CrossRef

49.

Rose SMSF, Contrepois K, Moneghetti KJ, Zhou W, Mishra T, Mataroso S, et al. A longitudinal big data approach for precision health. Nat Med. 2019;25:792–804. https://doi.org/10.1038/s41591-019-0414-6.CrossRef

Titel: Klinefelter Syndrome and Diabetes
verfasst von: Mark J. O’Connor
Emma A. Snyder
Frances J. Hayes
Publikationsdatum: 01.09.2019
Verlag: Springer US
Erschienen in: Current Diabetes Reports / Ausgabe 9/2019
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-019-1197-3

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2019

Nutritional Supplementation for the Prevention and/or Treatment of Gestational Diabetes Mellitus

Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes

Use of Insulin in the Inpatient Setting: Need for Continued Use

Scaling Up Teleophthalmology for Diabetic Eye Screening: Opportunities for Widespread Implementation in the USA

How Recent Advances in Genomics Improve Precision Diagnosis and Personalized Care of Maturity-Onset Diabetes of the Young