Context: There are very limited data available concerning the relationships between fetuin-A, weight status, non-alcoholic fatty liver disease (NAFLD), and features of the metabolic syndrome (MetS) in obese humans and especially in children.

Objective: To study the longitudinal relationships between fetuin-A, NAFLD, and MetS in obese children.

Design: One-year longitudinal follow-up study.

Setting: Primary care.

Patients: Thirty-six obese and 14 lean children.

Intervention: Outpatient one-year intervention program based on exercise, behavior and nutrition therapy.

Main Outcomes Measures: Changes of weight status (SDS-BMI), waist circumference, fetuin-A, blood pressure, lipids, transaminases, insulin resistance index HOMA, and prevalence of NAFLD (defined by liver ultrasound).

Results: The 12 obese children with NAFLD had significantly higher fetuin-A levels (0.35±0.07g/l) than the 24 obese children without NAFLD (0.29±0.06g/l) and the 14 normal weight children (0.29±0.05g/l). Fetuin-A levels were independent of age, pubertal stage, and gender. Fetuin-A correlated significantly to systolic (r=0.50) and diastolic blood pressure (r=0.41), insulin resistance index HOMA (r=0.28), and HDL-cholesterol (r=-0.31). Changes of fetuin-A correlated significantly to changes of insulin resistance index HOMA (r=0.34), systolic (r=0.31) and diastolic blood pressure (r=0.37), and waist circumferences (r=0.36). Substantial weight loss in 21 children led to a significant decrease of fetuin-A and the prevalence of NAFLD in contrast to the 15 children without substantial weight loss.

Conclusion: Fetuin-A levels were higher in children with NAFLD and were related to insulin resistance and to features of the MetS in both cross-sectional and longitudinal analyses. Therefore, fetuin-A might be a new promising link between obesity and its comorbidities.