ArticleFrontiers in endocrinology2026
External validation reveals setting-dependent performance of TyG-related indices for HbA1c-defined prediabetes.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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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