Abstract / Summary
Background Despite optimal low-density lipoprotein cholesterol (LDL-C) management, residual vascular risk remains high in patients with type 2 diabetes (T2D). Remnant cholesterol (RC) is an atherogenic lipid fraction, yet its longitudinal association with diabetic retinopathy (DR) remains insufficiently characterised. We aimed to evaluate whether longitudinal RC measurements independently predict new-onset DR.Materials and Methods We recruited 1,580 Chinese adults with T2D and no DR from a community-based prospective cohort established between 2017 and 2019. Participants were followed annually until 2023. Association between RC and incident DR was evaluated using time-dependent Cox regression models. We specifically examined this association among participants who achieved clinical targets for conventional lipid panel.Results We observed 304 incident DR cases during five follow-up visits. Each one-unit increase in natural log-transformed RC was associated with a 26% higher risk of new-onset DR (adjusted hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.08–1.47). Elevated RC (≥0.8 mmol/L) was associated with a 50% increased DR risk (aHR 1.50, 95% CI 1.11–2.03). These associations persisted among participants meeting guideline-recommended targets for triglycerides, LDL-C, and high-density lipoprotein cholesterol. Such associations were more prominent in women and patients with longer duration of T2D (p for interaction <0.05).Conclusions Elevated RC is an independent risk factor for new-onset DR and represents an important contributor to residual risk in patients with otherwise optimal lipid profiles. These findings suggest that RC merits consideration for integration into routine metabolic monitoring to improve DR risk stratification, particularly among female patients and those with long-standing diabetes.