Age at type 2 diabetes onset, retinol binding protein 4 and risks of diabetic retinopathy: a real-world cross-sectional study

Objective This study aimed to investigate the interaction between age at type 2 diabetes mellitus (T2DM) onset and serum retinol-binding protein 4 (RBP4) levels in relation to the risk of diabetic retinopathy (DR), examining whether RBP4 can serve as a potential biomarker for DR, particularly among patients with younger onset diabetes. Methods A cross-sectional analysis was conducted with 6,996 adults diagnosed with T2DM from the electronic medical records at Lishui People’s Hospital, Zhejiang, between January 2018 and June 2023. Participants were stratified by age at T2DM onset (< 65 years vs. ≥65 years) and serum RBP4 levels (< 40 vs. ≥40 pg/mL). The primary outcome was the presence of DR assessed through standardized fundus photography according to ETDRS criteria. Logistic regression models were employed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for DR. Results Elevated RBP4 levels (≥ 40 pg/mL) were significantly associated with an increased risk of DR among patients diagnosed with diabetes before 65 years of age (adjusted OR: 1.25, 95% CI: 1.10–1.42). Conversely, patients diagnosed at age 65 or older exhibited a reduced risk of DR associated with higher RBP4 levels (adjusted OR: 0.45, 95% CI: 0.33–0.61). Further subgroup analyses revealed significant interactions based on age groups (P for interaction < 0.001). Compared with younger-onset individuals, older-onset diabetic patients consistently demonstrated lower odds of DR, suggesting age as a critical determinant of DR risk. Conclusions Our findings underscore the age-dependent role of serum RBP4 as a biomarker for DR, indicating its predictive relevance primarily among younger diabetic patients. Age at diabetes onset emerges as a predominant factor influencing DR risk. These results advocate age-specific risk stratification and tailored management strategies to prevent diabetic retinopathy.