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Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

Abstract

Purpose

Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population.

Methods

We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate.

Results

Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system.

Conclusion

Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.

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Fig. 1

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Correspondence to Antonio Cittadini.

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Dr. A.S. receives research grant support from Cardiopath. The remaining authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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These authors contributed equally: Andrea Salzano and Roberta D’Assante.

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Salzano, A., D’Assante, R., Heaney, L.M. et al. Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives. Endocrine 61, 194–203 (2018). https://doi.org/10.1007/s12020-018-1584-6

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Keywords

  • Klinefelter syndrome
  • Diabetes mellitus
  • Metabolic syndrome
  • Insulin resistance
  • Testosterone therapy
  • Cardiovascular diseases