Metabolism and Type 2 Diabetes Across Life Stages in Klinefelter Syndrome: A Population-Based Cohort Study
Main finding · Incidence of metabolic conditionsResult — go to the resultHazard ratio 2.56 CI 1.85–3.44Authors' conclusion
The 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.
Study context
- Population
- Men with Klinefelter syndrome (KS) and male controls, Danish national registries, January 1994 to December 2022508 age-matched strata
- Exposure
- KS vs male controls
- Controlsn = 46,241reference
- Outcome
- Incidence and severity of metabolic disorders
Methodological detailsnational Danish registry-based, risk set matched, inverse probability weighting
- National Danish registry-based
- Risk set matched
- Inverse probability weighting
Main finding
Incidence of metabolic conditions
Hazard ratio
2.56
CI 1.85–3.44
KSvs Controls
HR 2.56 (CI 1.85–3.44)
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | HR (CI) | |
|---|---|---|
| Late-stage diabetes complicationsU-KSvs T-KS | 2.83 (1.33–6.02) | |
| All-cause mortality after T2D diagnosisD-KSvs Controls | 1.77 (1.28–2.45) | |
| All-cause mortality after T2D diagnosisT-KSvs ControlsNondifferential | 1.30 (0.68–2.48) | |
| 0.10.31310Hazard ratio (log scale) |
Late-stage diabetes complications
- U-KS had the most severe metabolic phenotype, with more obesity
Parenteral vs transdermal testosterone in T-KS
- Pattern of less obesity and T2D, but more hypertension and hypercholesterolemia, with parenteral vs transdermal testosterone
- Inverse probability weighting
Original publication
Metabolism and Type 2 Diabetes Across Life Stages in Klinefelter Syndrome: A Population-Based Cohort Study. J Clin Endocrinol Metab. Published 15 November 2025. doi:10.
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