Evidence map›Paper›PMID 42981609›Full record

ArticleJACC. Advances2026

Midlife Metabolic Syndrome as Mediator Between Early-Life Insulin Resistance and Later-Life Cardiovascular Diseases.

Chuyue Wu, Nathan D Wong, Liwei Chen, Wenjun Fan, Marissa J Seamans, Hua Zhou, Roch A Nianogo

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Article in JACC. Advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Chuyue WuDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California, USA. Electronic address: chuyuewu@g.ucla.edu.
Nathan D WongDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California, USA; Mary and Steve Wen Cardiovascular Division, Department of Medicine, University of California, Irvine, California, USA; Department of Epidemiology and Biostatistics, Joe C. Wen School of Population & Public Health, University of California, Irvine, California, USA.
Liwei ChenDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Wenjun FanMary and Steve Wen Cardiovascular Division, Department of Medicine, University of California, Irvine, California, USA; Department of Epidemiology and Biostatistics, Joe C. Wen School of Population & Public Health, University of California, Irvine, California, USA.
Marissa J SeamansDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Hua ZhouDepartment of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, USA.
Roch A NianogoDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California, USA; California Center for Population Research, UCLA, Los Angeles, California, USA.

Funding

The SMART-CV Study: Systems Modeling Approaches to Reducing Disparities in Cardiovascular DiseasesK01MD014163 · NIMHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI NIANOGO, ROCH · 2020 to 2024
$671k
NIMHD NIH HHS K01 MD014163
6 · The paper itself

Abstract

backgroundThe cardiovascular-kidney-metabolic syndrome framework describes progression from early metabolic dysfunction to clinical cardiovascular disease. Insulin resistance (IR) in young adulthood may contribute to later atherosclerotic cardiovascular disease (ASCVD), but the extent to which this association is mediated through midlife metabolic syndrome (MetS) remains unclear.

objectivesWe aimed to evaluate the association between young-adulthood IR and later-life ASCVD and quantify mediation through midlife MetS.

methodsWe analyzed 3,622 Black and White participants in the Coronary Artery Risk Development in Young Adults study who were aged 18 to 30 years at baseline and free of ASCVD through year 20. IR was defined as a Homeostatic Model Assessment of Insulin Resistance value at or above the 75th percentile (≥2.67). MetS was assessed at year 20, and ASCVD events were ascertained through year 35. Parametric g-computation with pooled logistic regression estimated total and mediated effects on cumulative ASCVD risk at the end of follow-up, accounting for midlife lifestyle factors as exposure-induced mediator-outcome confounders.

resultsAt baseline, 907 of 3,622 participants (25%) had IR. During a median follow-up of 14 years (Q1-Q3: 14-14 years) after year 20, 143 of 3,622 (3.9%) participants experienced an ASCVD event. Young-adulthood IR was associated with a 1.50-fold higher ASCVD risk at the end of follow-up (95% CI: 1.13-2.01), with 63.4% of the association mediated through midlife MetS (indirect risk ratio: 1.29; 95% CI: 1.13-1.48).

conclusionsYoung-adulthood IR was associated with higher later-life ASCVD risk, with a substantial proportion mediated through midlife MetS. These findings suggest early identification of IR and prevention of progression to MetS may help reduce long-term cardiovascular risk.

Indexed as

atherosclerotic cardiovascular diseaseinsulin resistancemediation analysismetabolic syndrome

Identifiers

PMID42981609
PMCPMC13753565

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