Association of TyG-related indices with cardiometabolic multimorbidity across early cardiovascular-kidney-metabolic syndrome stages 0–3: a prospective cohort study
Abstract
Cardiovascular–kidney–metabolic (CKM) syndrome is a systemic condition characterized by interrelated cardiac, renal, and metabolic disturbances. The triglyceride–glucose (TyG) index and several of its anthropometry-based derivatives have been increasingly recognized as surrogate markers of insulin resistance and potential predictors of cardiometabolic multimorbidity (CMM). However, whether their predictive performance differs across CKM stages 0–3 remains unclear. This prospective cohort investigation enrolled 646 participants without established CMM at baseline. CKM stages were classified according to AHA criteria based on obesity, metabolic abnormalities, kidney dysfunction, and subclinical cardiovascular disease. Five surrogate indicators of insulin resistance were examined, including the TyG index and four anthropometry-based TyG-derived indices. To evaluate model discrimination over time, Harrell’s time-dependent C-statistics were calculated. Improvements in predictive performance were further assessed by estimating the net reclassification index (NRI) and the integrated discrimination index (IDI). Restricted cubic spline functions were additionally fitted to depict potential dose–response relationships between each TyG-related measure and incident CMM. During a four-year follow-up, 21.36% of participants developed CMM. All TyG-related indices were significantly associated with increased CMM risk, displaying clear linear dose–response patterns. Among participants classified as CKM stage 3, TyG-WWI (TyG–weight-adjusted waist index) showed a robust association with CMM. Among all indicators, TyG-WWI and TyG-WHtR (TyG–waist-to-height ratio) showed relatively better discrimination, with meaningful improvements in NRI and IDI compared with the TyG index alone. Across CKM stages 0–3, the TyG index and its derivative markers showed consistent and independent associations with incident CMM. TyG-WWI and TyG-WHtR exhibited relatively better discrimination, highlighting their potential utility for early identification of high-risk individuals in community screening contexts, though their direct clinical applicability requires further validation.
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BibTeX
@article{chen2026association,
title = {{Association of TyG-related indices with cardiometabolic multimorbidity across early cardiovascular-kidney-metabolic syndrome stages 0–3: a prospective cohort study}},
author = {Ankai Chen and Haosen Pan and Guijun Liu and Xinxiang Dong and Xintao Chen and Fulai Sun and Sukhee Ahn and Liping Ren and Maoyun Miao},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73597-2},
url = {https://www.nature.com/articles/s41598-026-73597-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association of TyG-related indices with cardiometabolic multimorbidity across early cardiovascular-kidney-metabolic syndrome stages 0–3: a prospective cohort study
AU - Ankai Chen
AU - Haosen Pan
AU - Guijun Liu
AU - Xinxiang Dong
AU - Xintao Chen
AU - Fulai Sun
AU - Sukhee Ahn
AU - Liping Ren
AU - Maoyun Miao
PY - 2026
DA - 2026/10/17
JO - Scientific Reports
DO - 10.1038/s41598-026-73597-2
UR - https://www.nature.com/articles/s41598-026-73597-2
AB - Cardiovascular–kidney–metabolic (CKM) syndrome is a systemic condition characterized by interrelated cardiac, renal, and metabolic disturbances. The triglyceride–glucose (TyG) index and several of its anthropometry-based derivatives have been increasingly recognized as surrogate markers of insulin resistance and potential predictors of cardiometabolic multimorbidity (CMM). However, whether their predictive performance differs across CKM stages 0–3 remains unclear. This prospective cohort investigation enrolled 646 participants without established CMM at baseline. CKM stages were classified according to AHA criteria based on obesity, metabolic abnormalities, kidney dysfunction, and subclinical cardiovascular disease. Five surrogate indicators of insulin resistance were examined, including the TyG index and four anthropometry-based TyG-derived indices. To evaluate model discrimination over time, Harrell’s time-dependent C-statistics were calculated. Improvements in predictive performance were further assessed by estimating the net reclassification index (NRI) and the integrated discrimination index (IDI). Restricted cubic spline functions were additionally fitted to depict potential dose–response relationships between each TyG-related measure and incident CMM. During a four-year follow-up, 21.36% of participants developed CMM. All TyG-related indices were significantly associated with increased CMM risk, displaying clear linear dose–response patterns. Among participants classified as CKM stage 3, TyG-WWI (TyG–weight-adjusted waist index) showed a robust association with CMM. Among all indicators, TyG-WWI and TyG-WHtR (TyG–waist-to-height ratio) showed relatively better discrimination, with meaningful improvements in NRI and IDI compared with the TyG index alone. Across CKM stages 0–3, the TyG index and its derivative markers showed consistent and independent associations with incident CMM. TyG-WWI and TyG-WHtR exhibited relatively better discrimination, highlighting their potential utility for early identification of high-risk individuals in community screening contexts, though their direct clinical applicability requires further validation.
SN - 2045-2322
ER -