Experimental Gerontology (Jun 2025)

The role of oxidative stress in the association between metabolic score for insulin resistance and stroke: evidence from two large population-based studies

  • Yi Tan,
  • Xing Lin,
  • Liquan Xie

DOI
https://doi.org/10.1016/j.exger.2025.112761
Journal volume & issue
Vol. 205
p. 112761

Abstract

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Objective: This study endeavors to unveil the association between the Metabolic Score for Insulin Resistance (METS-IR) and stroke among adults utilizing data of the National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS), and whether oxidative stress (OS) mediates their association. Methods: Our study cohort comprised 101,316 individuals from NHANES and 17,708 individuals from CHARLS. The intricate relationships among the METS-IR, stroke, and OS biomarkers were evaluated via logistic regression, restricted cubic splines (RCS), as well as mediation analysis. Results: The final analysis included 22,542 American and 9521 Chinese participants, among whom 844 and 887 were diagnosed with stroke, respectively. Regression analysis indicated a positive association of METS-IR with stroke [NHANES: OR = 1.01, 95 % CI (1.01, 1.02), p < 0.001; CHARLS: OR = 1.02, 95 % CI (1.02, 1.03), p < 0.001], with higher METS-IR quartiles being associated with elevated stroke incidence [NHANES: OR = 1.39, 95 % CI (1.11, 1.73), p = 0.004; CHARLS: OR = 1.74, 95 % CI (1.39, 2.17), p < 0.001]. Participants with elevated METS-IR and serum uric acid (SUA) exhibited the greatest probability of stroke. Mediation analysis proved that OS partially mediated this association [Mediation effect: NHANES β = −8.45e−5, 95 % CI (−1.41e−4, −4.01e−5), p < 0.001; CHARLS β = −4.02e−5, 95 % CI (−8.14e−5, −7.76e−6), p = 0.012]. Conclusion: The METS-IR was positively associated with stroke in NHANES and CHARLS cohorts, and OS partially mediated this association.

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