Retrospective Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2025; 16(8): 108671
Published online Aug 15, 2025. doi: 10.4239/wjd.v16.i8.108671
Metabolic score for insulin resistance is associated with adverse cardiovascular events in patients with type 2 diabetes
Ying Xin, Na-Ling Peng, Cai-Yan Xin, Jiang-Rong Liao, Xin-Qun Hu, Yi-Heng Dong, Xiang-Yu Zhang
Ying Xin, Xin-Qun Hu, Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Ying Xin, Na-Ling Peng, Jiang-Rong Liao, Yi-Heng Dong, Xiang-Yu Zhang, Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
Cai-Yan Xin, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
Co-first authors: Ying Xin and Na-Ling Peng.
Co-corresponding authors: Yi-Heng Dong and Xiang-Yu Zhang.
Author contributions: Xin Y, Peng NL, Xin CY, and Dong YH analyzed the data; Xin Y and Peng NL wrote the paper, they contributed equally to this article, they are the co-first authors of this manuscript; Xin CY, Liao JR, and Dong YH edited the paper; Hu XQ, Dong YH, and Zhang XY defined the study theme and methods; Dong YH and Zhang XY contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors read and approved the final manuscript.
Supported by the Key Research and Development Plan of Hunan Province, No. 2022SK2013; and Central South University, No. 2024ZZTS0931.
Institutional review board statement: The study was exempt from ethical review and approval, as no additional institutional review board approval was necessary for the secondary analysis.
Informed consent statement: The data for our study are derived from the Action to Control Cardiovascular Risk in Diabetes. All participants completed informed consent forms before participating in the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and analyzed during the current study are available from the Action to Control Cardiovascular Risk in Diabetes (ACCORD)/ ACCORDION Research Materials obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center. The contents of this report do not necessarily reflect the opinions or views of the ACCORD/ ACCORDION authors or the National Heart, Lung, and Blood Institute.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiang-Yu Zhang, Department of Geriatrics, The Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. xiangyuzhang@csu.edu.cn
Received: April 21, 2025
Revised: May 22, 2025
Accepted: July 7, 2025
Published online: August 15, 2025
Processing time: 116 Days and 19.1 Hours
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.

Keywords: Metabolic score for insulin resistance; Cardiovascular disease; Type 2 diabetes; Atherosclerosis; Insulin resistance

Core Tip: This research demonstrates that metabolic score for insulin resistance is significantly associated with adverse cardiovascular events in patients with type 2 diabetes mellitus. As a comprehensive metabolic indicator, metabolic score for insulin resistance may offer valuable insights for cardiovascular risk assessment, stratification, and outcome prediction - particularly in high-risk populations where traditional methods may be insufficient.