Early metabolic and hepatic alterations in children with Down syndrome: a hidden risk beyond BMI

OBJECTIVES: Children and adolescents with Down syndrome (DS) are at increased risk of cardiometabolic impairment, but this vulnerability may not be adequately captured by body mass index (BMI) alone. This study aimed to characterize anthropometric, metabolic, and hepatic alterations in pediatric DS beyond conventional BMI-based assessment. METHODS: We included 95 children and adolescents aged 5-18 years: 48 with DS and 47 controls. Anthropometric assessment included weight, height, waist circumference, BMI z-score, waist-to-height ratio (WHtR), and predicted body composition. Fasting blood samples were analyzed for glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride-glucose (TyG) index, lipid profile, and liver enzymes. Between-group differences were assessed using age- and sex-adjusted analysis of covariance, while multivariate analyses identified the variables contributing most strongly to group discrimination. RESULTS: Compared with controls, children with DS showed no significant difference in BMI z-score, but had higher WHtR and % fat mass and lower % fat-free mass (p<0.05). They also exhibited a less favorable metabolic profile, with higher fasting glucose, HOMA-IR, and TyG index, lower HDL-cholesterol, higher triglycerides, and higher liver enzyme levels (p<0.05). Multivariate analyses confirmed that liver enzymes, glycemic markers, HDL-cholesterol, and WHtR were the strongest contributors to group separation. CONCLUSIONS: Children and adolescents with DS display an early high-risk cardiometabolic phenotype characterized by altered body composition, insulin resistance, dyslipidemia, and biochemical signs of hepatic involvement only partly reflected by BMI. These findings support broader metabolic surveillance in pediatric DS to improve early risk stratification and guide preventive interventions.