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

To examine the association between serum retinol-binding protein 4 (RBP4) and diabetic retinopathy (DR), and to assess whether age at type 2 diabetes mellitus (T2DM) onset modifies this association. This cross-sectional study included 6,996 adults with T2DM identified from electronic medical records at Lishui People’s Hospital, Zhejiang, between 2018 and 2023. Participants were stratified by age at diabetes onset (< 65 vs. ≥ 65 years) and serum RBP4 levels (< 40 vs. ≥ 40 pg/mL). DR was assessed using standardized fundus photography according to ETDRS criteria. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with interaction analyses performed to assess effect modification. Higher RBP4 levels (≥ 40 pg/mL) were associated with higher odds of DR in both age-at-onset strata. In adjusted analyses, the OR was 1.28 (95% CI 1.12–1.45) among participants with T2DM onset < 65 years and 1.43 (95% CI 0.96–2.12) among those with onset ≥ 65 years. However, the formal interaction by categorical age at T2DM onset (< 65 vs. ≥ 65 years) was not statistically significant (P for interaction = 0.58). Participants with onset ≥ 65 years had a shorter diabetes duration than those with onset < 65 years, which may partly explain the lower burden of DR in the later-onset group. In subgroup analyses, diabetes duration showed a statistically significant interaction with RBP4, although the stratum-specific ORs were very similar. Higher serum RBP4 was associated with higher odds of DR in adults with T2DM. However, we found no clear evidence that this association differed materially between the categorical age-at-onset groups. These findings support serum RBP4 as a potential biomarker candidate for DR risk and underscore the importance of diabetes duration when interpreting retinopathy risk.