Higher metabolic score for insulin resistance (METS-IR) was significantly associated with greater risks of major cardiovascular events (MACE), heart failure, and mortality in patients with type 2 diabetes (T2D), a study finds. The study identified a dose-dependent relationship between rising METS-IR and cardiovascular outcomes, with the highest quartile more than doubling the risk of heart failure compared with the lowest.
This multicenter randomized controlled study is published in the World Journal of Diabetes.
A higher metabolic score for insulin resistance (METS-IR) was significantly associated with greater risks of major cardiovascular events (MACE), heart failure, and mortality in patients with type 2 diabetes mellitus (T2DM). | Image credit: inthasone – stock.adobe.com
“The present study examines the association of the METS-IR with cardiovascular outcomes among individuals with established T2DM,” wrote the researchers of the study. “Our findings demonstrated that elevated baseline METS-IR predicts subsequent adverse cardiovascular events, with particular significance for CHF [congestive heart failure], robust to adjustment for conventional cardiovascular risk factors.”
Diabetes is a chronic condition characterized by insufficient insulin production or impaired insulin utilization.2 Individuals with T2D face a substantially higher risk of cardiovascular disease and related mortality compared with those without diabetes. Much of this elevated risk is linked to the increased prevalence of established cardiovascular risk factors such as hypertension, dyslipidemia, and obesity, which are commonly observed in patients with T2D.
The study utilized a secondary analysis of data derived from a large multicenter randomized controlled trial, including 10,191 patients with T2D between the ages of 40 and 79 years, with a median follow-up of approximately 10 years.1 Baseline METS-IR was calculated for all participants using triglyceride levels, body mass index, high-density lipoprotein cholesterol, and fasting plasma glucose. Cardiovascular outcomes of interest included MACE, cardiovascular death, all-cause mortality, congestive heart failure, and major coronary heart disease events.
Statistical analyses were performed across METS-IR quartiles, with multivariable adjustments applied to account for potential confounders. To evaluate the incremental predictive value of METS-IR, model performance was compared against conventional risk prediction tools.
Patients in the highest METS-IR quartile had a 25% greater risk of MACEs compared with those in the lowest quartile (HR, 1.25; 95% CI, 1.08-1.45).
Similarly, the highest quartile was associated with a 55% higher risk of cardiovascular death (HR, 1.55; 95% CI, 1.23-1.96), a 39% increased risk of all-cause mortality (HR, 1.39; 95% CI, 1.21-1.59), more than double the risk of congestive heart failure (HR, 2.22; 95% CI, 1.74-2.82), and a 35% higher risk of major coronary heart disease (HR, 1.35; 95% CI, 1.17-1.56).
However, the researchers noted some limitations, including its retrospective design and the use of baseline METS-IR only, without tracking changes over time. Furthermore, the findings may have limited generalizability beyond US patients aged 40 to 79 years.
Despite these limitations, the researchers believe the study findings support incorporating METS-IR into conventional risk models to improve predictive accuracy, supporting its role as an independent and clinically meaningful predictor of cardiovascular risk in patients with T2D.
“Serving as an integrative metabolic marker, METS-IR could offer important insights for evaluating cardiovascular risk, especially in high-risk groups where conventional approaches fall short,” wrote the researchers. “Continued research is needed to further investigate the clinical applications of METS-IR and to confirm its utility in cardiovascular risk prediction.”
References
1. Xin Y, Peng NL, Xin CY, et al. Metabolic score for insulin resistance is associated with adverse cardiovascular events in patients with type 2 diabetes. World J Diabetes. 2025;16(8):108671. doi:10.4239/wjd.v16.i8.108671
2. Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A, et al. Type 2 diabetes and cardiovascular disease: have all risk factors the same strength? World J Diabetes. 2014;5(4):444-70. doi:10.4239/wjd.v5.i4.444