Study on the correlation between SPISE-IR, METs-IR, TyG and short-term adverse cardiovascular events in patients with heart failure and diabetes mellitus
- 1Second Affiliated Hospital, Zhejiang Chinese Medical University , ,
Abstract
Objective: Heart failure (HF) patients with type 2 diabetes mellitus (T2DM) are at high risk of short-term major adverse cardiovascular events (MACE). Insulin resistance (IR) is a key shared mechanism, yet simple prognostic markers remain limited. This multicenter retrospective cohort study compared three IR surrogate indices (SPISE-IR, METs-IR, and TyG) for predicting 18-month post-discharge MACE in hospitalized HF-T2DM patients, aiming to identify practical tools for risk stratification.
Methods: A total of 477 hospitalized HF-T2DM patients from two tertiary hospitals in Zhejiang (2018–2024) were enrolled according to unified criteria. Baseline clinical, laboratory, echocardiographic, and medication data were collected to calculate SPISE-IR, METs-IR, and TyG. The primary outcome was 18-month post-discharge composite MACE. Associations were evaluated using Cox regression and RCS, while predictive performance was assessed by ROC and PR curves, DCA, NRI, IDI, and subgroup analyses.
Results: Of 477 patients, 191 (40.04%) experienced MACE over 18 months, including 3 cardiovascular deaths. Patients with MACE were older, had lower LVEF, worse renal function, and higher NT-proBNP (all p < 0.05). On multivariable analysis, SPISE-IR (HR 9.31, 95% CI 5.96–14.55, p < 0.001) and METs-IR (HR 1.07, 95% CI 1.05–1.09, p < 0.001) were associated with MACE, whereas TyG was not (HR 1.19, 95% CI 0.95–1.49, p = 0.127). SPISE-IR and METs-IR showed significant nonlinear dose–response relationships and yielded AUCs of 0.790 and 0.801, respectively, versus 0.539 for TyG. Higher SPISE-IR and METs-IR quartiles were associated with progressively higher cumulative event risk (log-rank p < 0.001), whereas no significant between-quartile difference was observed for TyG. Adding either index to the baseline model significantly improved NRI and IDI (all p < 0.05); SPISE-IR showed numerically larger NRI and IDI improvements than METs-IR. Subgroup analyses showed a consistent SPISE-IR association, whereas METs-IR exhibited effect modification by age, sex, smoking status, and hypertension; TyG remained largely non-significant. Heart failure rehospitalization accounted for 138 of 191 MACE (72.3%). After exclusion of 24 recurrent-angina events, SPISE-IR (HR 10.83, 95% CI 6.71–17.45) and METs-IR (HR 1.07, 95% CI 1.06–1.09) remained associated with the strict MACE endpoint (both p < 0.001). After 1,000 bootstrap resamples, optimism-corrected AUCs were 0.818 for the clinical + SPISE-IR model and 0.806 for the clinical + METs-IR model. In center-based external validation, their AUCs were 0.804 and 0.806, respectively.
Conclusion: SPISE-IR and METs-IR are associated with 18-month MACE risk in hospitalized HF-T2DM patients and show better predictive performance than TyG. These indices may provide additional value for risk stratification in this population.
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BibTeX
@article{deng2026study,
title = {{Study on the correlation between SPISE-IR, METs-IR, TyG and short-term adverse cardiovascular events in patients with heart failure and diabetes mellitus}},
author = {Haoxuan Deng and Qiyue Zhu and Changjin Lin and Wei Qiu and Yunyan Zhang and Junyi Hua},
journal = {Frontiers in nutrition},
year = {2026},
month = oct,
doi = {10.3389/fnut.2026.1938459},
url = {https://europepmc.org/article/PMC/PMC13719381},
note = {CC BY},
}
RIS
TY - JOUR
TI - Study on the correlation between SPISE-IR, METs-IR, TyG and short-term adverse cardiovascular events in patients with heart failure and diabetes mellitus
AU - Haoxuan Deng
AU - Qiyue Zhu
AU - Changjin Lin
AU - Wei Qiu
AU - Yunyan Zhang
AU - Junyi Hua
PY - 2026
DA - 2026/10/16
JO - Frontiers in nutrition
DO - 10.3389/fnut.2026.1938459
UR - https://europepmc.org/article/PMC/PMC13719381
AB - Objective: Heart failure (HF) patients with type 2 diabetes mellitus (T2DM) are at high risk of short-term major adverse cardiovascular events (MACE). Insulin resistance (IR) is a key shared mechanism, yet simple prognostic markers remain limited. This multicenter retrospective cohort study compared three IR surrogate indices (SPISE-IR, METs-IR, and TyG) for predicting 18-month post-discharge MACE in hospitalized HF-T2DM patients, aiming to identify practical tools for risk stratification. Methods: A total of 477 hospitalized HF-T2DM patients from two tertiary hospitals in Zhejiang (2018–2024) were enrolled according to unified criteria. Baseline clinical, laboratory, echocardiographic, and medication data were collected to calculate SPISE-IR, METs-IR, and TyG. The primary outcome was 18-month post-discharge composite MACE. Associations were evaluated using Cox regression and RCS, while predictive performance was assessed by ROC and PR curves, DCA, NRI, IDI, and subgroup analyses. Results: Of 477 patients, 191 (40.04%) experienced MACE over 18 months, including 3 cardiovascular deaths. Patients with MACE were older, had lower LVEF, worse renal function, and higher NT-proBNP (all p < 0.05). On multivariable analysis, SPISE-IR (HR 9.31, 95% CI 5.96–14.55, p < 0.001) and METs-IR (HR 1.07, 95% CI 1.05–1.09, p < 0.001) were associated with MACE, whereas TyG was not (HR 1.19, 95% CI 0.95–1.49, p = 0.127). SPISE-IR and METs-IR showed significant nonlinear dose–response relationships and yielded AUCs of 0.790 and 0.801, respectively, versus 0.539 for TyG. Higher SPISE-IR and METs-IR quartiles were associated with progressively higher cumulative event risk (log-rank p < 0.001), whereas no significant between-quartile difference was observed for TyG. Adding either index to the baseline model significantly improved NRI and IDI (all p < 0.05); SPISE-IR showed numerically larger NRI and IDI improvements than METs-IR. Subgroup analyses showed a consistent SPISE-IR association, whereas METs-IR exhibited effect modification by age, sex, smoking status, and hypertension; TyG remained largely non-significant. Heart failure rehospitalization accounted for 138 of 191 MACE (72.3%). After exclusion of 24 recurrent-angina events, SPISE-IR (HR 10.83, 95% CI 6.71–17.45) and METs-IR (HR 1.07, 95% CI 1.06–1.09) remained associated with the strict MACE endpoint (both p < 0.001). After 1,000 bootstrap resamples, optimism-corrected AUCs were 0.818 for the clinical + SPISE-IR model and 0.806 for the clinical + METs-IR model. In center-based external validation, their AUCs were 0.804 and 0.806, respectively. Conclusion: SPISE-IR and METs-IR are associated with 18-month MACE risk in hospitalized HF-T2DM patients and show better predictive performance than TyG. These indices may provide additional value for risk stratification in this population.
SN - 2296-861X
ER -