Midlife Metabolic Syndrome as Mediator Between Early-Life Insulin Resistance and Later-Life Cardiovascular Diseases
Authors' conclusion
Young-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.
Study context
- Population
- Black and White participants aged 18 to 30 years at baseline and free of atherosclerotic cardiovascular disease (ASCVD) through year 20
- Participants
- 3,622 participants
- Comparison
- Young-adulthood insulin resistance (IR) and later-life ASCVD, mediated through midlife metabolic syndrome (MetS)
- IRn = 907
- Outcome
- ASCVD events
- Follow-up
- Median 14 years (Q1-Q3: 14-14 years) after year 20
Methodological detailsparametric g-computation with pooled logistic regression, mediation analysis
- Parametric g-computation with pooled logistic regression
- Mediation analysis
Main finding
As reported in the abstract
Participants experienced an ASCVD event
143 of 3,622
3.9%
Further findings
Cumulative ASCVD risk at the end of follow-up
- Young-adulthood IR: fold higher ASCVD risk
- 1.50 (95% CI 1.13-2.01)
- Proportion of the association mediated through midlife MetS
- 63.4%
- Indirect risk ratio through midlife MetS
- 1.29 (95% CI 1.13-1.48)
IR at baseline
- Participants with IR
- 907 of 3,622 participants (25%)
Original publication
Midlife Metabolic Syndrome as Mediator Between Early-Life Insulin Resistance and Later-Life Cardiovascular Diseases. JACC Adv. Published 4 November 2026. doi:10.
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