External validation reveals setting-dependent performance of TyG-related indices for HbA1c-defined prediabetes
- 1Laboratory Department, Pu’er Hospital of Traditional Chinese Medicine
Abstract
Background and objective: Prediabetes defined by glycated haemoglobin (HbA1c) can occur despite fasting plasma glucose (FPG) below 100 mg/dL, leaving a discordant glycaemic phenotype that FPG-based pathways may miss. We investigated whether triglyceride–glucose (TyG)-related indices identify this phenotype and whether their comparative performance is maintained across populations.
Methods: We analysed fasting-subsample data from seven US National Health and Nutrition Examination Survey (NHANES 2005–2018) cycles and an independent health-examination cohort from Pu’er Hospital of Traditional Chinese Medicine (2020–2026). The primary index was TyG–waist-to-height ratio (TyG–WHtR). Survey-weighted and local regression models quantified adjusted associations. Candidate prediction models were benchmarked against related metabolic indices and a model retaining FPG, triglycerides and WHtR as separate terms. Repeated cross-validation was performed in NHANES, after which all fitted models, transformations and thresholds were frozen for external validation.
Results and conclusion: Among 6,930 eligible NHANES participants, 1,206 had HbA1c-defined prediabetes, corresponding to a weighted prevalence of 12.7% [95% confidence interval (CI), 11.7%–13.7%]. The local cohort included 10,791 participants and 1,139 outcomes. Each cohort-specific standard deviation increase in TyG–WHtR was associated with higher outcome prevalence in NHANES (prevalence ratio, 1.239; 95% CI, 1.158–1.326) and locally (1.482; 1.407–1.561). The raw-component model showed repeated internal validation (area under the receiver operating characteristic curve, 0.746), whereas the metabolic score for insulin resistance led to frozen external validation (0.710; 0.693–0.727). TyG–WHtR was reproducibly associated with the outcome but was not the strongest discriminator in either setting. The gains in discrimination were modest, and this cross-sectional validation does not establish clinical utility.
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BibTeX
@article{li2026external,
title = {{External validation reveals setting-dependent performance of TyG-related indices for HbA1c-defined prediabetes}},
author = {Fen Li and Yingjing Xie and Yu Chen and Zexiu Wang and Chunmei Rao and Jinliu Cheng and Tianwu Zhang and Jin Yuan},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1961688},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1961688/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - External validation reveals setting-dependent performance of TyG-related indices for HbA1c-defined prediabetes
AU - Fen Li
AU - Yingjing Xie
AU - Yu Chen
AU - Zexiu Wang
AU - Chunmei Rao
AU - Jinliu Cheng
AU - Tianwu Zhang
AU - Jin Yuan
PY - 2026
DA - 2026/10/08
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1961688
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1961688/full
AB - Background and objective: Prediabetes defined by glycated haemoglobin (HbA1c) can occur despite fasting plasma glucose (FPG) below 100 mg/dL, leaving a discordant glycaemic phenotype that FPG-based pathways may miss. We investigated whether triglyceride–glucose (TyG)-related indices identify this phenotype and whether their comparative performance is maintained across populations. Methods: We analysed fasting-subsample data from seven US National Health and Nutrition Examination Survey (NHANES 2005–2018) cycles and an independent health-examination cohort from Pu’er Hospital of Traditional Chinese Medicine (2020–2026). The primary index was TyG–waist-to-height ratio (TyG–WHtR). Survey-weighted and local regression models quantified adjusted associations. Candidate prediction models were benchmarked against related metabolic indices and a model retaining FPG, triglycerides and WHtR as separate terms. Repeated cross-validation was performed in NHANES, after which all fitted models, transformations and thresholds were frozen for external validation. Results and conclusion: Among 6,930 eligible NHANES participants, 1,206 had HbA1c-defined prediabetes, corresponding to a weighted prevalence of 12.7% [95% confidence interval (CI), 11.7%–13.7%]. The local cohort included 10,791 participants and 1,139 outcomes. Each cohort-specific standard deviation increase in TyG–WHtR was associated with higher outcome prevalence in NHANES (prevalence ratio, 1.239; 95% CI, 1.158–1.326) and locally (1.482; 1.407–1.561). The raw-component model showed repeated internal validation (area under the receiver operating characteristic curve, 0.746), whereas the metabolic score for insulin resistance led to frozen external validation (0.710; 0.693–0.727). TyG–WHtR was reproducibly associated with the outcome but was not the strongest discriminator in either setting. The gains in discrimination were modest, and this cross-sectional validation does not establish clinical utility.
SN - 1664-2392
ER -