Skip to main content
Top
Published in: Current Diabetes Reports 9/2019

01-09-2019 | Insulins | Other Forms of Diabetes and Its Complications (JJ Nolan and H Thabit, Section Editors)

Klinefelter Syndrome and Diabetes

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

Published in: Current Diabetes Reports | Issue 9/2019

Login to get access

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.
Literature
3.
go back to reference Plunkett ER, Barr ML. Testicular dysgenesis affecting the seminiferous tubules principally, with chromatin-positive nuclei. Lancet. 1956;271:2853–4. Plunkett ER, Barr ML. Testicular dysgenesis affecting the seminiferous tubules principally, with chromatin-positive nuclei. Lancet. 1956;271:2853–4.
4.
go back to reference Barr ML. The natural history of Klinefelter’s syndrome. Fertil Steril. 1966;17:429–41.CrossRef Barr ML. The natural history of Klinefelter’s syndrome. Fertil Steril. 1966;17:429–41.CrossRef
5.
go back to reference Jacobs PA, Strong JA. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature. 1959;183:302–3.CrossRef Jacobs PA, Strong JA. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature. 1959;183:302–3.CrossRef
9.
go back to reference 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. 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.
11.
go back to reference •• 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 •• 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
15.
19.
go back to reference 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 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
41.
go back to reference • 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 • 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.
go back to reference • 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 • 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
46.
go back to reference 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 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
48.
go back to reference 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 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
Metadata
Title
Klinefelter Syndrome and Diabetes
Authors
Mark J. O’Connor
Emma A. Snyder
Frances J. Hayes
Publication date
01-09-2019
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 9/2019
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-019-1197-3

Other articles of this Issue 9/2019

Current Diabetes Reports 9/2019 Go to the issue

Pathogenesis of Type 1 Diabetes (A Pugliese and SJ Richardson, Section Editors)

Extracellular Vesicles in Type 1 Diabetes: Messengers and Regulators

Microvascular Complications—Retinopathy (DL Chao and G Yiu, Section Editors)

Treatment of Diabetic Macular Edema

Pathogenesis of Type 2 Diabetes and Insulin Resistance (M-E Patti, Section Editor)

The Beta Cell in Type 2 Diabetes

Pathogenesis of Type 2 Diabetes and Insulin Resistance (M-E Patti, Section Editor)

Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes

Economics and Policy in Diabetes (AA Baig and N Laiteerapong, Section Editors)

Economics of Beta-Cell Replacement Therapy

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.