Adherence to three EAT‑Lancet diet indices and progression to advanced cardiovascular‑kidney‑metabolic syndrome: a Middle Eastern cohort study with mediation by insulin resistance and inflammation

The cardiovascular–kidney–metabolic (CKM) framework conceptualizes cardiometabolic risk, chronic kidney disease, and cardiovascular disease as a staged continuum driven by interrelated pathophysiology. Although higher-quality dietary patterns are consistently associated with more favorable cardiometabolic profiles, prospective evidence linking sustainable dietary patterns—specifically the EAT–Lancet planetary health diet—to progression across CKM stages is limited. We investigated whether greater adherence to the planetary health diet is associated with lower risk of transitioning from early CKM (stages 0–2) to advanced CKM (stages 3–4). We analyzed data from 5,757 adults with early CKM (stages 0–2) (49.9% men; mean age 42.6 years) in the MMRT cohort (2017–2023). Dietary intake was assessed using a validated 125-item food frequency questionnaire. Adherence to the EAT–Lancet diet was operationalized primarily using the planetary health diet index (PHDI) (0–150), with two alternatives EAT–Lancet indices evaluated for robustness. Incident advanced CKM was defined per 2023 American Heart Association criteria. Multivariable logistic regression estimated odds ratios (ORs) across PHDI quartiles and per SD, adjusting for demographic, socioeconomic, lifestyle, and dietary factors. Mediation analysis was assessed using product-of-coefficients methods with bootstrap confidence intervals. During a median follow‑up of 5 years, 458 participants progressed to advanced CKM. In fully adjusted models, participants in the highest versus lowest PHDI quartile had 29% lower odds of advanced CKM (OR = 0.71; 95% CI 0.53–0.94; P for trend = 0.003). Each SD higher PHDI was associated with lower odds (OR = 0.87; 95% CI 0.78–0.97). Dose–response patterns were broadly linear (P-nonlinearity = 0.06, P-overall < 0.01). Stronger inverse associations emerged among younger individuals, those with overweight/obesity, non-smokers, and participants with lower physical activity or wealth (all P-interaction < 0.05). Findings were directionally consistent using alternative EAT–Lancet indices. Mediation analyses suggested that HOMA-IR and CRP accounted for 44.5% and 37.9% of the total association, respectively, with smaller contribution from the triglyceride-to-HDL ratio and no significant mediation by uric acid. Greater adherence to the planetary health diet was prospectively associated with reduced CKM progression, largely via improved insulin sensitivity and reduced systemic inflammation. These findings support plant-forward dietary patterns as a potential strategy to slow CKM advancement.