Ferritin and Soluble Transferrin Receptor Beyond Inflammation: Independent Associations with Fasting Glucose and...

Background/Objectives: Metabolic syndrome (MetS) is a major global public health concern associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. Iron metabolism has been implicated, but the storage (ferritin) and functional (soluble transferrin receptor, sTfR) axes are rarely assessed within a single model. We aimed to determine whether both axes are independently associated with glycaemia and MetS and to evaluate their diagnostic value. Materials and Methods: A cross-sectional study was conducted in 297 adults (72.8% women) from Turkestan, Kazakhstan. Hierarchical regression models with sequential adjustment were applied for age, sex, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), dietary inflammatory index (DII), HFE H63D genotype, and gamma-glutamyl transferase (GGT). Path analysis and receiver operating characteristic (ROC) analysis were also performed. Results: Ferritin and sTfR were independently associated with fasting glucose (β = 0.27 and 0.73, respectively) and metabolic syndrome (OR = 1.52 and 4.53, respectively). When analyzed separately, neither biomarker reached statistical significance for MetS (ferritin: OR = 1.20, p = 0.140; sTfR: OR = 1.93, p = 0.072). Ferritin demonstrated no discriminatory ability in men (AUC = 0.500, 95% CI 0.370-0.630) and modest discrimination in women (AUC = 0.652, 95% CI 0.571-0.732). GGT accounted for approximately 28% of the ferritin-glucose association in a path-analytic model. Ferritin, GGT, and HbA1c levels increased progressively even among individuals with 0-2 MetS components. Conclusions: Both the storage and functional axes of iron metabolism provide independent information on glycaemic status, but their associations become apparent only when assessed simultaneously. Ferritin alone is not suitable as a diagnostic marker for metabolic syndrome.