Associations of metabolic score for insulin resistance with type 2 diabetes, cancer, and all-cause mortality: a meta-analysis of cohort studies.

OBJECTIVE: Insulin resistance (IR) constitutes a central pathophysiological mechanism underlying a spectrum of chronic metabolic disorders. The Metabolic Score for Insulin Resistance (METS-IR), which integrates fasting blood glucose (FBG), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI), serves as a simple, cost-effective surrogate marker for IR. However, its associations with type 2 diabetes mellitus (T2DM), cancer, and all-cause mortality remain to be systematically synthesized. This study aims to systematically evaluate its clinical prognostic value. METHODS: We systematically searched PubMed, EMBASE, and Web of Science for prospective or retrospective cohort studies evaluating the associations of baseline METS-IR with incident T2DM, cancer, or all-cause mortality. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and linear and nonlinear dose-response meta-analyses were performed. Heterogeneity, robustness, and publication bias were additionally assessed. RESULTS: A total of 23 cohort studies were included. For T2DM (6 studies), the highest METS-IR category was associated with a substantially elevated risk compared with the lowest category (HR = 4.03, 95% CI: 2.57-6.33), and per 1-standard deviation (1-SD) increment in METS-IR corresponded to a 48% higher risk (HR = 1.48, 95% CI: 1.24-1.77); dose-response analysis revealed a significant nonlinear increasing relationship (P for nonlinearity< 0.001). For cancer (5 studies), per 1-SD increment in METS-IR was associated with a 21% higher risk of cancer (HR = 1.21, 95% CI: 1.10-1.34); dose-response analysis indicated a significant nonlinear association (P for nonlinearity = 0.042). For all-cause mortality (13 studies), per 1-SD rise in METS-IR was linked to an 8% increased risk of all-cause death (HR = 1.08, 95% CI: 1.03-1.14); dose-response analysis demonstrated an overall linear increasing trend (P for linearity = 0.029), with each 20-unit increase in METS-IR associated with an approximately 2.8% higher risk of all-cause mortality (HR = 1.028, 95% CI: 1.004-1.056). CONCLUSIONS: Elevated METS-IR levels are significantly associated with a nonlinear, progressive increase in the risk of incident T2DM. Its associations with cancer and all-cause mortality are weaker and more complex yet still exhibit consistent directional trends. METS-IR represents a convenient, readily applicable tool for early identification of metabolic risk using routine clinical parameters; however, its prognostic value for cancer and all-cause mortality merits further validation in large-scale, long-term follow-up studies.Systematic review registration: PROSPERO, identifier CRD420261293948.