Association of Estimated Glucose Disposal Rate and Risk of Age-Related Macular Degeneration: Evidence from the UK Biobank

The association between insulin resistance (IR) and age-related macular degeneration (AMD) risk remains unclear. This study examined the impact of estimated glucose disposal rate (eGDR), an IR indicator, on AMD development and explored the potential mediating role of systemic inflammation. This prospective cohort study included 429,844 participants from the UK Biobank with available eGDR data and no AMD at baseline. Cox proportional hazard models were used to evaluate the eGDR-AMD association, while restricted cubic spline (RCS) plots were employed to investigate the shape of this relationship. Exploratory mediation analysis was conducted to examine the contribution of systemic inflammatory markers to the association. During a median follow-up of 13.4 years, 6,828 individuals developed AMD. Higher eGDR was linked to a 13% reduced AMD risk per standard deviation increase (HR: 0.87; 95% CI: 0.84–0.91; p < 0.001), with an L-shaped relationship observed (P-overall < 0.001; P-non-linear = 0.013). Systemic inflammatory markers (C-reactive protein, neutrophils, neutrophil-lymphocyte ratio, systemic immune-inflammatory index) mediated only a small proportion (0.3%–6.6%) of the eGDR-AMD association. Higher eGDR, as a surrogate marker of IR, is associated with a modestly lower risk of incident AMD, with systemic inflammation explaining only a small proportion of this association. Any mechanistic interpretation or clinical implication of this observational association requires further validation in future studies.