Diet quality assessed by healthy eating index and its association with metabolic aging: mediation by systemic immune-inflammation index

Background Metabolic aging is characterized by insulin resistance, adverse lipid metabolism, and chronic low-grade inflammation, and is associated with higher risks of type 2 diabetes, cardiovascular disease, and mortality. Although diet quality may be related to these processes, evidence on the statistical role of systemic inflammation and the reproducibility of the association in a non-U. S. clinical setting remains limited. Objective To examine the association between diet quality, assessed by the healthy eating index-2015 (HEI), and metabolic aging markers, and to evaluate whether the Systemic Immune-Inflammation Index (SII) statistically partially accounts for this association in NHANES and in an external hospital-based cohort from China. Methods We conducted a cross-sectional analysis of 15,314 adults aged ≥20 years from NHANES 2005–2020 and an external hospital-based cohort of 833 adults who underwent health examination in Shandong, China, during 2024–2025. Metabolic aging was assessed by Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Atherogenic Index of Plasma (AIP). SII was calculated as platelet × neutrophil/lymphocyte counts. Multivariable linear regression, restricted cubic spline analyses, and statistical mediation analyses were performed. In the external cohort, HEI-2015 was used as a harmonized diet-quality metric to reproduce the same exposure definition, while acknowledging that it does not fully capture culture-specific dietary patterns. Results Higher HEI scores were inversely associated with HOMA-IR ( β = −0.70, 95% CI: −1.10 to −0.30, p 0.01) and AIP ( β = −0.06, 95% CI: −0.08 to −0.04, p 0.01) in NHANES. SII statistically accounted for 7.3 and 10.5% of the observed associations for HOMA-IR and AIP, respectively. Similar inverse associations were also observed in the external cohort, where the mediated proportions were larger. Conclusion Higher diet quality was associated with lower metabolic aging markers, and SII statistically partially accounted for these associations. The external cohort reproduced the direction of the associations in a distinct Chinese clinical setting, but cultural differences and the cross-sectional design warrant cautious interpretation.