Biological aging and the incidence and progression of diabetic retinopathy and kidney disease in type 2 diabetes mellitus: A prospective cohort study.

AIMS: We examined whether phenotypic age (PhenoAge) acceleration was associated with the incidence and progression of diabetic retinopathy (DR) and diabetic kidney disease (DKD). METHODS: In 8,194 adults with T2DM, PhenoAge was calculated from nine routine biomarkers at baseline and follow-up. DR was deep-learning graded and DKD met Kidney Disease: Improving Global Outcomes criteria. Associations of PhenoAge acceleration and longitudinal change with incident DR/DKD, concurrent DR-DKD, and progression were estimated using modified Poisson models adjusted for conventional risk factors. RESULTS: Compared with participants in the lowest tertile, those in the highest tertile of baseline PhenoAge acceleration had higher risks of incident DR (RR 1.56, 95% CI 1.10-2.23), DKD (RR 1.30, 1.10-1.54), and concurrent DR and DKD (RR 3.24, 1.56-6.76). Among participants with baseline DR or DKD, respectively, those in the highest tertile of PhenoAge acceleration had an increased risk of DKD progression (RR 2.04, 1.60-2.59), but not DR progression. Longitudinal increases in PhenoAge acceleration were associated with incident DKD (RR 1.36, 1.14-1.62), while decreases in PhenoAge acceleration were associated with lower DKD progression risk (RR 0.59, 0.41-0.85). CONCLUSIONS: PhenoAge acceleration, a routine biomarker-based measure of biological aging, was associated with microvascular complications in T2DM.