Metabolic score for insulin resistance is associated with adverse cardiovascular events in patients with type 2 diabetes.

Abstract

Background: Cardiovascular disease represents a major complication in patients with type 2 diabetes mellitus (T2DM), with insulin resistance (IR) recognized as a key underlying pathophysiological mechanism. The metabolic score for IR (METS-IR), a simple, non-invasive, and insulin-independent surrogate marker of IR, has been validated for risk stratification and prognostic assessment in conditions such as hypertension, ischemic cardiomyopathy, and T2DM. Monitoring fluctuations in METS-IR levels among individuals with T2DM may facilitate early identification of elevated cardiovascular risk and inform timely therapeutic adjustments.

Aim: To investigate the association between METS-IR and cardiovascular risk in patients with T2DM and to evaluate its potential utility as a predictive biomarker.

Methods: This study represents a secondary analysis of a multicenter randomized controlled trial, ultimately including 10191 patients with T2DM aged 40 years to 79 years, with a follow-up duration of approximately 10 years. Baseline METS-IR was calculated using triglycerides, body mass index, high-density lipoprotein cholesterol and fasting plasma glucose. The predictive value of METS-IR for major adverse cardiovascular events (MACEs), all-cause mortality, congestive heart failure, and major coronary heart disease events, was assessed using Cox proportional hazards models, restricted cubic spline analysis, and stratified subgroup analyses. Multivariable adjustments were performed to account for potential confounding factors.

Results: The incidence of MACEs increased steadily across higher METS-IR quartiles. After adjusting for multiple confounding factors, hazard ratios comparing the highest to the lowest METS-IR quartile were 1.25 [95% confidence interval (CI): 1.08-1.45] for MACEs, 1.55 (95%CI: 1.23-1.96) for cardiovascular death, 1.39 (95%CI: 1.21-1.59) for all-cause mortality, 2.22 (95%CI: 1.74-2.82) for congestive heart failure, and 1.35 (95%CI: 1.17-1.56) for major coronary heart disease. Restricted cubic spline analysis supported a positive, dose-dependent relationship between rising METS-IR levels and cardiovascular risk. Moreover, adding METS-IR to conventional risk prediction models enhanced their performance, as evidenced by improvements in the C-statistic, net reclassification improvement, and integrated discrimination improvement. Subgroup analyses indicated possible interactions between METS-IR, hemoglobin A1c levels, and aspirin therapy.

Conclusion: METS-IR shows a strong correlation with cardiovascular risk in individuals with T2DM. Tracking METS-IR levels could enhance risk assessment and the prediction of cardiovascular events.