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Klinefelter Syndrome and Diabetes


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.


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.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Correspondence to Frances J. Hayes.

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This article is part of the Topical Collection on Other Forms of Diabetes and Its Complications

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O’Connor, M.J., Snyder, E.A. & Hayes, F.J. Klinefelter Syndrome and Diabetes. Curr Diab Rep 19, 71 (2019).

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  • Klinefelter syndrome
  • Sex chromosome aneuploidy
  • Type 2 diabetes
  • Insulin resistance
  • Testosterone replacement therapy