Metabolic score for insulin resistance and the incidence of cardiovascular disease: a meta-analysis of cohort studies.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of cohort studies.
PubMed 41180178 · doi:10.3389/fendo.2025.1699985
What was done
Authors conducted a systematic review and meta-analysis of cohort studies from PubMed, EMBASE, Cochrane Library, and Web of Science up to August 2, 2025. They examined the relationship between baseline metabolic score for insulin resistance (METS-IR)—a non-insulin-based surrogate calculated from fasting glucose, triglycerides, HDL cholesterol, and BMI—and incident composite cardiovascular disease (CVD), coronary artery disease (CAD), and stroke in adults without baseline CVD. Random-effects models were used to calculate pooled hazard ratios (HRs) for highest versus lowest METS-IR categories and per standard deviation (SD) increment. Nonlinear dose-response relationships were evaluated with restricted cubic splines.
What was found
Eight cohort studies comprising 437,283 participants were included. Comparing highest versus lowest METS-IR categories showed significantly elevated risk for: - Composite CVD: HR 1.65 (95% CI: 1.36–2.02; I² = 85.6%) - CAD: HR 1.82 (95% CI: 1.50–2.20; I² = 59.7%) - Stroke: HR 1.47 (95% CI: 1.19–1.83; I² = 76.3%) Per SD increment in METS-IR: - Composite CVD: HR 1.16 (95% CI: 1.10–1.22; I² = 70.7%) - CAD: HR 1.18 (95% CI: 1.11–1.25; I² = 52.4%) - Stroke: HR 1.13 (95% CI: 1.06–1.19; I² = 67.9%) Nonlinear dose-response analyses demonstrated a nonlinear relationship for CAD (P = 0.011) and marginal nonlinearity for stroke (P = 0.072), with inflection points at METS-IR values of 40.56 (composite CVD), 38.24 (CAD), and 48.88 (stroke), above which risk accelerated.
Why it matters
METS-IR is an accessible, routinely measurable marker that independently predicts CVD, CAD, and stroke incidence without requiring fasting insulin assays. Identifying specific nonlinear thresholds provides practical targets for metabolic risk stratification.
Limits
All included data were observational cohorts, precluding causal conclusions. Statistical heterogeneity across studies was moderate to high (I² between 52.4% and 85.6%). The abstract does not specify follow-up duration, geographic distribution, or how thoroughly individual studies adjusted for potential confounders.
Cited by
- supports Insulin resistance is a causal driver of systemic endothelial dysfunction and cardiovascular dysfunction.