ArticleThe Journal of clinical endocrinology and metabolism2026
Metabolism and Type 2 Diabetes Across Life Stages in Klinefelter Syndrome: A Population-Based Cohort Study.
Article in The Journal of clinical endocrinology and metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Metabolism and Type 2 Diabetes Across Life Stages in Klinefelter Syndrome: A Population-Based Cohort Study.The Journal of clinical endocrinology and metabolism · 2026Article
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5 authors.
Funding
Abstract
contextKlinefelter syndrome (KS) is underdiagnosed, undertreated, and associated with metabolic dysfunction.
objectiveWe compared incidences of metabolic disorders among men with KS, either undiagnosed (U-KS), diagnosed and untreated (D-KS), or treated with testosterone replacement therapy (T-KS).
methodsThis was a national Danish registry-based study from January 1994 to December 2022. We computed hazard ratios (HR) for incidence and severity of metabolic disorders between risk set matched strata of U-KS, D-KS, and T-KS and male control individuals. We evaluated the effect of parenteral vs transdermal testosterone supplementation on incidence of metabolic disorders in T-KS, applying inverse probability weighting.
resultsWe included 508 age-matched strata of U-KS, D-KS, and T-KS, and included 46 241 male controls. Incidence of metabolic conditions was more than 2-fold increased in KS, including type 2 diabetes (HR 2.56 [1.85-3.44]). U-KS presented with the most severe metabolic phenotype, with more obesity and more late-stage diabetes complications compared with T-KS (HR 2.83 [1.33-6.02]). All-cause mortality following diagnosis of type 2 diabetes was increased in D-KS compared with controls (HR 1.77 [1.28-2.45]), but nondifferential for T-KS and controls (HR 1.30 [0.68-2.48]). We saw a pattern of less obesity and type 2 diabetes, but more hypertension and hypercholesterolemia, with parenteral vs transdermal testosterone supplementation in T-KS.
conclusionThe metabolic profile in men with KS is dependent on diagnosis and treatment status, with pronounced metabolic dysfunction in U-KS. Better diagnosis and treatment of KS are needed to alleviate metabolic dysfunction and improve survival in men with KS.
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