A J-shaped association between serum ferritin and type 2 diabetes risk, significantly modified by anemia status: A large cross-sectional study with restricted cubic spline analysis

BackgroundElevated serum ferritin is associated with an increased risk of Type 2 Diabetes Mellitus (T2DM), but the precise dose-response relationship, particularly potential non-linear patterns and the modifying role of erythrocyte parameters, remains unclear.MethodsThis cross-sectional study enrolled 4,148 participants, of whom 775 had T2DM (18.7%). We used multivariable logistic regression, with restricted cubic splines (RCS), to analyze the non-linear association between log10-transformed ferritin and T2DM risk, incorporating interaction terms for erythrocyte parameters. Robustness was confirmed using stratified analysis and propensity score weighting (PSW).ResultsSerum ferritin levels were significantly higher in the T2DM group (P < 0.001). RCS analysis revealed a J-shaped relationship between log 10-transformed ferritin and T2DM risk (P for non-linearity < 0.001), with an inflection point at a ferritin level of approximately 316 μg/L, beyond which the risk increased sharply. An S-shaped association was observed between MCV and T2DM risk. Subgroup analysis demonstrated a significant inverse association in non-anemic participants (OR = 0.149, 95% CI: 0.063-0.350), whereas a positive trend was observed in anemic participants (OR = 2.999, 95% CI: 0.616-14.588). After PSW adjustment, high ferritin was confirmed as an independent risk factor for T2DM (OR = 2.212, 95% CI: 1.655-2.956).ConclusionA non-linear, J-shaped relationship exists between ferritin and T2DM risk, suggesting a threshold effect. This relationship is significantly modified by individual anemia status. These findings emphasize the necessity of considering both ferritin's non-linear effects and anemia status in T2DM risk assessment, providing new evidence for the complex role of iron metabolism in metabolic disease pathogenesis.