Healthy diet and slower biological aging as protective factors against microvascular complications in type 2 diabetes

This study aimed to evaluate the independent and joint effects of adherence to healthy dietary patterns and slower biological aging on the incidence of diabetic microvascular complications in individuals with type 2 diabetes mellitus (T2DM), and to assess the mediating role of biological aging. In a prospective cohort of 13,294 T2DM participants without baseline DMCs, dietary quality was assessed using a validated 10-point score, while biological aging was calculated from nine biomarkers and chronological age. Cox regression models were used to assess associations, and mediation analysis was performed to estimate the mediating effects of biological aging. Over a mean follow-up of 11.9 years, 3197 participants developed DMCs, including 1392 cases of diabetic retinopathy (DR), 1908 of diabetic nephropathy (DN), and 598 of diabetic neuropathy (DPN). Higher dietary scores (6-10) were associated with reduced risks of composite DMCs (HR 0.845; 95% CI 0.742-0.962), DR (0.804; 0.659-0.981), and DN (0.766; 0.643-0.911), but not DPN. Phenotypic age acceleration (PhenoAgeAccel) ≤ 0 was also linked to a reduced risk of DMCs. In addition, biologically younger with higher dietary score (6-10 points) had 39.4%, 30.8%, 53.6%, and 41.9% lower risk of composite DMCs, DR, DN, and DPN, respectively. Mediation analysis revealed that PhenoAgeAccel accounted for 43.0%, 29.8%, and 33.5% of the diet association with composite DMCs, DR, and DN, respectively. The results suggest that healthier dietary patterns and slower biological aging can reduce the risk of DMCs in T2DM patients, with a substantial portion of the dietary benefits mediated through slower aging. Integrating dietary and aging-targeted interventions may offer a promising method to reduce DMC risk in T2DM.