NAFLD and hyperinsulinemia are major determinants of serum ferritin levels

Background/Aims There is an increasing body of evidence that serum ferritin is associated with the metabolic syndrome. However, no study has tested for NAFLD. The aim was to test the assumption that the association between serum ferritin and the metabolic syndrome is mediated by NAFLD. Methods A cross-sectional study of a sub-sample of the first Israeli national health survey. Exclusion criteria were any known etiology for secondary NAFLD. Participants underwent an abdominal ultrasound (US), biochemical tests, and dietary and anthropometric evaluations. Results Three hundred and forty-nine subjects were included in the analysis. Serum ferritin was higher in the NAFLD group (92.4 ± 63.1 vs. 65.1 ± 58.0, P < 0.001). After adjusting for age and gender, the following variables were significantly associated with increased ferritin levels: abdominal obesity, hyperglycemia, hyperinsulinemia, HOMA, hypertriglyceridemia and the metabolic syndrome itself. After further adjusting for NAFLD, only abdominal obesity [2.1 (1.1–3.9)] and hyperinsulinemia [2.3 (1.3–4.2)] were still significantly associated with ferritin. In a multivariate analysis the interaction between NAFLD and hyperinsulinemia was the second strongest predictor of serum ferritin (P = 0.005). Conclusions The association between serum ferritin and the metabolic syndrome is mediated by undiagnosed NAFLD. The interaction between NAFLD and hyperinsulinemia is a major determinant of serum ferritin levels at the population level.