ArticleTherapeutic advances in endocrinology and metabolism2026
Association between the ratio of uric acid to high-density lipoprotein cholesterol (UHR) and the abnormal risk of sarcopenia: Evidence from two large population-based surveys and interpretable machine learning-driven sarcopenia screening.
Article in Therapeutic advances in endocrinology and metabolism, 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: Sarcopenia is a geriatric syndrome linked to nutritional intake, chronic inflammation and metabolic dysregulation. While uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are recognized biomarkers, their specific relationship with sarcopenia remains debated. The uric acid-to-HDL-C ratio (UHR) has emerged as a novel, integrated biomarker. This study investigates the UHR-sarcopenia association using representative US and South Korean populations and develops an interpretable machine learning screening framework. Objectives: To investigate the association between UHR and sarcopenia in two nationally representative populations and to develop and externally validate an interpretable machine-learning model for sarcopenia screening. Design: A population-based cross-sectional study using NHANES 2011-2018 as the primary cohort and KNHANES 2024 as the external validation cohort. Methods: This cross-sectional study included 7,314 participants from NHANES (2011-2018) and 3,274 from KNHANES (2024). The UHR-sarcopenia relationship was evaluated using multivariable logistic regression, smooth curve fitting, and subgroup analyses. To develop a screening model for prevalent sarcopenia, feature selection was performed using LASSO regression and the Boruta algorithm. Machine learning models were trained on the NHANES cohort, interpreted using SHAP values, and rigorously validated externally using the KNHANES dataset. Results: Higher UHR was significantly associated with greater odds of prevalent sarcopenia. In fully adjusted models, participants in the highest UHR quartile had higher odds of sarcopenia than those in the lowest quartile in NHANES (OR 2.014, 95% CI 1.552-2.625; P<0.001) and KNHANES (OR 1.658, 95% CI 1.183-2.342; P=0.004). Among seven machine-learning models, LightGBM demonstrated the most balanced performance, achieving an AUC of 0.810 in NHANES and maintaining good discrimination during external validation in KNHANES (AUC 0.823). Conclusions: Elevated UHR is significantly associated with sarcopenia. The UHR-integrated LightGBM model demonstrates robust discriminative capacity, serving as a practical and interpretable tool for sarcopenia screening in clinical practice.
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