Biological aging and incident cardiovascular diseases in individuals with diabetes: insights from a large prospective cohort study

BACKGROUND: Biological aging is a critical risk factor of age-related diseases, but its impact on diabetic individuals remains unclear. This study aimed to examine the associations of biological aging with the incident cardiovascular diseases (CVDs) and life expectancy loss in diabetic individuals. METHODS: We included 12,828 diabetic individuals in UK biobank. Biological aging was calculated by Klemera-Doubal method Biological Age (KDMAge) and phenotypic age (PhenoAge). Cox proportional hazard models were fitted to investigate the associations of biological aging with incident coronary heart disease (CHD), atrial fibrillation (AF), heart failure (HF), stroke, and degenerative valvular heart disease (VHD) in diabetic individuals. We also evaluated life expectancy loss in accelerated aging individuals, the interactions between biological aging and clonal hematopoiesis of indeterminate potential (CHIP), and performed causal mediation analysis. RESULTS: During a median follow-up of 13.1 years, we documented 3794 incident CVDs in diabetic individuals. PhenoAge accelerated aging was significantly associated with all CVD subtypes, with hazard ratios ranging from 1.23 to 1.62, and KDMAge showed even stronger associations. Accelerated biological aging was also associated with over 2 years of life expectancy loss. CHIP and PhenoAge accelerated aging had a significant synergistic effect on CHD, HF, and VHD. Inflammatory activation contributed significantly to accelerated aging-associated CHD and HF. CONCLUSIONS: Biological aging significantly increases CVD risk and reduces life expectancy in diabetic population, with effects modified by CHIP status. Targeting biological aging mechanisms may help prevent CVDs and premature mortality in diabetic population.