Biological age acceleration, genetic susceptibility, and incident diabetic retinopathy risk: A prospective cohort...

Diabetic retinopathy (DR) remains a major microvascular complication of diabetes, and conventional risk factors do not fully explain individual differences in disease risk. This study investigated the associations of biological age acceleration with incident DR.

This prospective cohort study included 12,608 UK Biobank participants with diabetes. Three biological age acceleration measures, including phenotypic age acceleration (PhenoAgeAccel), Klemera-Doubal method Biological Age acceleration (KDMAccel), and Gompertz Law-Based Biological Age difference (GOLD BioAgeDiff), were evaluated. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DR. Joint effects with polygenic risk score were further assessed. Analyses were also repeated in the general population.

Higher biological age acceleration was consistently associated with an increased risk of incident DR. Per 5-year increase, the fully adjusted HRs were 1.32 (95% CI, 1.26-1.38) for PhenoAgeAccel, 1.13 (95% CI, 1.11-1.16) for KDMAccel, and 1.20 (95% CI, 1.16-1.24) for GOLD BioAgeDiff. Participants with both high genetic risk and accelerated biological aging had the highest risk of DR, and additive interaction was observed between biological age acceleration and genetic susceptibility. Similar patterns were observed in the general population.

The results suggest that accelerated biological aging is associated with a higher risk of incident DR and may have potential relevance for DR risk stratification.