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.