Life’s Essential 8 is associated with slower biological ageing and lower diabetic nephropathy burden in type 2 diabetes: a nationally representative study

Background We aimed to examine cross-sectional associations of cardiovascular health (CVH), summarised by the American Heart Association Life’s Essential 8 (LE8), with biological ageing and microvascular complications in type 2 diabetes (T2DM). Additionally, we sought to quantify the extent to which aging metrics statistically mediate these associations. Methods We analysed 4,390 U.S. adults with T2DM from NHANES 1999–2020 using survey weights. LE8 (0-100) was computed according to the American Heart Association algorithm. Biological ageing was indexed by Klemera-Doubal age acceleration (KDM-AA), PhenoAge acceleration (PhenoAgeAccel), and log-transformed homeostatic dysregulation (HD-log). Survey-weighted linear models were employed to assess the relationship between LE8 and ageing metrics, while survey-weighted logistic models were used for associations between LE8 and prevalent diabetic nephropathy (DN) and self-reported diabetic retinopathy (DR). Restricted cubic splines were utilized to assess non-linearity, and prespecified subgroup analyses explored effect modification. Counterfactual mediation analyses partitioned total associations into indirect (via ageing metrics) and direct components. Results Higher LE8 was consistently associated with a more favourable ageing profile and a lower microvascular complication burden. For each 10-point increment in LE8, adjusted mean differences (95% CI) were: KDM-AA − 1.77 years (− 1.94 to − 1.59), PhenoAgeAccel − 1.23 years (− 1.36 to − 1.10), and HD-log − 0.23 (− 0.25 to − 0.21). Each 10-point higher LE8 related to lower odds of DN (OR 0.80, 95% CI 0.75–0.86) and DR (OR 0.85, 95% CI 0.75–0.95). Compared to low CVH, high CVH showed 64% lower odds of DN (OR 0.36, 95% CI 0.21–0.64). Dose-response curves were approximately linear. Furthermore, Ageing metrics mediated 64–85% of the LE8-DN association and 36–66% of the LE8-DR association. Conclusions Among U.S. adults with T2DM, better CVH is associated with slower biological ageing and a lower prevalence of DN, with more modest associations for DR. Mediation findings suggest ageing-related pathways may explain a substantial proportion of these associations. Public health strategies focused on improving LE8 domains could help to reduce microvascular complication burden; however, longitudinal and interventional studies are warranted to establish causality.