Klinefelter Syndrome and Diabetes

Curr Diab Rep. 2019 Jul 31;19(9):71. doi: 10.1007/s11892-019-1197-3.


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.

Keywords: Insulin resistance; Klinefelter syndrome; Sex chromosome aneuploidy; Testosterone replacement therapy; Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Androgens / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Hormone Replacement Therapy / methods
  • Humans
  • Insulin Resistance
  • Klinefelter Syndrome / complications
  • Klinefelter Syndrome / metabolism*
  • Male
  • Prevalence
  • Testosterone / therapeutic use


  • Androgens
  • Testosterone