High prevalence of cardiometabolic risk features in adolescents with 47,XXY/Klinefelter syndrome

Abstract

Klinefelter syndrome (KS) occurs in 1:600 males and is associated with high morbidity and mortality due to diabetes and cardiovascular disease. Up to 50% of men with KS have metabolic syndrome, a cluster of features conferring increased risk for diabetes and cardiovascular disease. These cardiometabolic (CM) risk features have not been studied in adolescents with KS. The objective of this cohort study was to compare CM risk features in adolescents with KS to controls matched for sex, age, and BMI z score. Fifty males with KS (age 10-17 years) were well-matched to male controls (n = 50) for age (14.0 ± 1.7 vs. 14.0 ± 1.5 years) and BMI z score (0.3 ± 1.3 vs. 0.4 ± 1.2). Three CM risk features were present in 30% of adolescents with KS compared to 12% of controls (RR 2.5, 95% CI 1.1-5.9, p = .048). The KS group had significantly lower HDL cholesterol (p = .006), higher triglycerides (p < .001), and greater waist circumference percentile (p < .001). Despite a normal BMI, the prevalence of CM risk features was very high in adolescents with KS, particularly for central adiposity and dyslipidemia. The pathophysiology of this metabolic profile independent of obesity needs further investigation to facilitate prevention of the high morbidity of cardiovascular disease and diabetes in this population. ClinicalTrials.gov identifiers: NCT01585831 and NCT02723305.

Keywords: Klinefelter syndrome; central adiposity; dyslipidemia; metabolic syndrome; sex chromosome aneuploidy.

© 2020 Wiley Periodicals, Inc.

Figures

FIGURE 1

Risk of meeting cutoff criteria for cardiometabolic (CM) risk features in adolescents with Klinefelter syndrome (KS) compared to sex-, age-, and BMI-matched controls. The point value represents the risk ratio (RR) and the error bars represent the 95% confidence intervals, with values >1 indicating an increased risk in KS. RRs for hyperglycemia could not be calculated as no participant in either group had a fasting blood glucose >110 mg/dl

FIGURE 2

Prevalence of cardiometabolic (CM) risk features in Klinefelter syndrome (KS) by testosterone replacement therapy (TRT) status and controls

FIGURE 3

Prevalence of three or more cardiometabolic (CM) risk factors in males with Klinefelter syndrome (KS)