Ferritin and Soluble Transferrin Receptor Beyond Inflammation: Independent Associations with Fasting Glucose and Metabolic Syndrome in a Central Asian Cohort.

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.