What is the clinical evidence from this study?

Study design: Cohort. Population: New-onset stroke (n=4344). Intervention: Cumulative metabolic score for insulin resistance (cumMETS-IR) vs. Lowest quartile of cumMETS-IR. Primary outcome: New-onset stroke (HR 1.72, 95% CI 1.22-2.42, p=0.002).

What question did this study set out to answer?

This research investigates the association between metabolic score for insulin resistance (METS-IR) and new-onset stroke in middle-aged and older adults.

June 12, 2026Cardiovascular Diabetology0 citationsOpen Access

Associations of metabolic score for insulin resistance and new-onset stroke in middle-aged and older adults: a national cohort study

XZXuexue ZhangShenzhen Pingle Orthopedic Hospital RWRui WeiPeking University HHHuanrong HuFirst Affiliated Hospital of Jiangxi Medical College

Key Result

The highest quartile of cumulative metabolic score for insulin resistance was associated with a significantly higher incidence of new-onset stroke compared to the lowest quartile (HR 1.72).

Key Points

This research investigates the association between metabolic score for insulin resistance (METS-IR) and new-onset stroke in middle-aged and older adults.
Utilized 4344 participants from the China Health and Retirement Longitudinal Study (CHARLS) with follow-up until 2020.
Calculated cumulative METS-IR (cumMETS-IR) as the area under the curve of METS-IR values from 2011-2015.
Employed Cox proportional hazards models and k-means clustering analysis to assess stroke incidence and change patterns.
385 new stroke events (8.86%) occurred over 5 years.
Cumulative METS-IR positively correlated with incident stroke (HR 1.72, 95% CI 1.22–2.42, P = 0.002).
The high-decreasing METS-IR pattern showed the highest stroke incidence (HR 1.61, 95% CI 1.08–2.42, P = 0.021).

Study Design

Type

Cohort (n=4,344)

Multicenter

Yes

Structured PICO

Does higher cumulative metabolic score for insulin resistance (cumMETS-IR) increase the risk of new-onset stroke in middle-aged and older adults?

Population

4,344 middle-aged and older Chinese adults without prior stroke were followed for a median of 5 years to assess the association between cumulative metabolic score for insulin resistance and incident stroke.

Exposure

Cumulative metabolic score for insulin resistance (cumMETS-IR) and METS-IR change patterns over time

Comparator

Lowest quartile of cumMETS-IR or low-stable METS-IR change pattern

Outcome

New-onset stroke (based on self-reported physician diagnosis)hard clinical

Cumulative metabolic score for insulin resistance and its change patterns over time are significantly associated with the risk of new-onset stroke in middle-aged and older Chinese adults.

Main Result

Hazard Ratio: 1.72 (95% CI 1.22–2.42)

p-value: p=0.002

Limitations

Incident stroke was defined using self-reported physician diagnosis rather than adjudicated clinical records or imaging-based confirmation.
Stroke subtype information was unavailable.
Time-to-event analysis was based on approximate event timing and may have been affected by interval censoring.
cumMETS-IR and clusters-based METS-IR change patterns were derived from only two measurements.
Residual confounding due to substantial baseline differences across groups and unmeasured factors cannot be excluded.
Generalizability to younger individuals or other ethnic populations requires further external validation.

Abstract

Metabolic score for insulin resistance (METS-IR) is acknowledged as a reliable indicator of insulin resistance and cardiometabolic risk. This study aims to explore the relationship between cumulative METS-IR (cumMETS-IR) and METS-IR change patterns with new-onset stroke. 4344 participants from the China Health and Retirement Longitudinal Study (CHARLS) with follow-up until 2020 were utilized in this study. cumMETS-IR was calculated as the area under the curve of METS-IR values from 2011 to 2015. K-means clustering analysis was employed to discern distinct METS-IR change patterns over this interval. Associations of cumMETS-IR and METS-IR change patterns with incident stroke were examined using Cox proportional hazards models and restricted cubic splines (RCS). Mediation analysis assessed whether diastolic blood pressure (DBP) accounted for the association between cumMETS-IR and incident stroke. There were 385 (8.86%) new stroke events over 5-years median follow-up. RCS analysis showed that cumMETS-IR was positively correlated with incident stroke ( P -overall = 0.013, P -nonlinear = 0.252). Compared with the lowest quartile, the highest quartile was associated with a higher incidence of stroke (adjusted hazard ratio HR 1.72, 95% confidence interval CI 1.22–2.42, P = 0.002). Four distinct METS-IR change patterns were identified using k-means clustering: low-stable (30.5%), low-to-moderate stable (35.9%), moderate-to-high stable (24.7%), and high-decreasing (8.9%). Participants following the high-decreasing pattern was associated with the highest incidence of stroke compared to those in the low-stable patterns (adjusted HR 1.61, 95% CI 1.08–2.42, P = 0.021). The core findings remained robust across a series of sensitivity analyses. Mediation analysis revealed that DBP partially explained this association, with a mediation proportion of 9.6%. Both cumMETS-IR and METS-IR change were associated with increased incidence of stroke in middle-aged and older Chinese adults. Monitoring changes in METS-IR over time may help characterize metabolic status more comprehensively and offer supportive information for stroke-related health assessment. Graphical abstract

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