Anemia modifies the association between albumin-corrected fructosamine and diabetic retinopathy in type 2 diabetes: a cross-sectional study

Abstract Background Albumin-corrected fructosamine (AlbF) reflects short-term glycemic exposure and is less affected by erythrocyte lifespan than glycated hemoglobin (HbA1c). Whether anemia influences the association between AlbF and diabetic retinopathy (DR) remains unclear. We investigated the modifying effect of anemia on the AlbF–DR association and evaluated the clinical utility of AlbF in patients with anemia. Methods In this cross-sectional study, 1,090 hospitalized patients with type 2 diabetes mellitus were enrolled. Multivariable logistic regression was used to examine the association between AlbF and DR. Effect modification by anemia was assessed on both multiplicative and additive scales. Among participants with anemia, the discriminative performance of AlbF and HbA1c was compared using area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results DR was present in 459 (42.1%) participants, and 366 (33.6%) met World Health Organization criteria for anemia. Among anemic participants, higher AlbF was independently associated with greater odds of DR (adjusted OR per 10 μmol/g increase, 1.98; 95% CI, 1.42–2.76; p < 0.001). Anemia significantly modified the AlbF–DR association on the multiplicative scale (P for interaction = 0.014). The association was stronger in participants with anemia (OR 1.98; 95% CI, 1.42–2.76) than in those without anemia (OR 1.30; 95% CI, 1.03–1.63). Significant additive interaction was also observed (RERI 2.88, AP 0.49, SI 2.42). In the anemic subgroup, adding AlbF significantly improved discrimination beyond the base model (AUC 87.07% vs. 84.43%, p = 0.012), whereas HbA1c did not. AlbF further improved risk classification and discrimination beyond HbA1c (categorical NRI 0.109, continuous NRI 0.461, and IDI 0.039; all p < 0.011). Conclusions Anemia significantly modified the association between AlbF and DR in patients with type 2 diabetes. Elevated AlbF was more strongly associated with DR among individuals with anemia, and AlbF provided incremental discriminative value beyond HbA1c in this subgroup. These findings support AlbF as a complementary glycemic marker in patients with anemia.