Cao Xiao, Xiao Xiaohua, Jiang Peipei, Fu Nian
Department of Gastroenterology, Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Diseases, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Front Med (Lausanne). 2025 Mar 28;12:1539708. doi: 10.3389/fmed.2025.1539708. eCollection 2025.
Effective biomarkers for the diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) remain limited. This study aims to evaluate the potential of advanced glycation end products (AGEs) and their endogenous secretory receptor (esRAGE) as non-invasive biomarkers for diagnosing MASLD, to explore differences between obese and non-obese MASLD patients, and to develop a novel diagnostic model based on these biomarkers.
This study enrolled 341 participants, including 246 MASLD patients (118 non-obese, 128 obese) and 95 healthy controls. Serum AGEs and esRAGE levels were measured by ELISA. Key predictors were identified using the Lasso algorithm, and a diagnostic model was developed with logistic regression and visualized as nomograms. Diagnostic accuracy and utility were evaluated through the area under the curve (AUC), bootstrap validation, calibration curves, and decision curve analysis (DCA).
Serum AGEs and esRAGE levels were significantly higher in MASLD patients compared to controls. Moreover, obese MASLD patients had higher esRAGE levels than non-obese ones, but no significant difference in AGEs levels was found. A diagnostic model incorporating age, WC, BMI, ALT, TG, HDL, AGEs, and esRAGE achieved an AUC of 0.963, with 94.3% sensitivity and 85.3% specificity. The AUC for bootstrap internal validation was 0.963 (95% CI: 0.944-0.982). Calibration curves showed strong predictive accuracy, and DCA demonstrated high net clinical benefit.
Serum AGEs and esRAGE serve as non-invasive biomarkers for distinguishing MASLD patients. We developed and validated diagnostic models for MASLD, offering valuable tools to identify at-risk populations and improve prevention and treatment strategies.
用于诊断代谢功能障碍相关脂肪性肝病(MASLD)的有效生物标志物仍然有限。本研究旨在评估晚期糖基化终末产物(AGEs)及其内源性分泌受体(esRAGE)作为诊断MASLD的非侵入性生物标志物的潜力,探讨肥胖与非肥胖MASLD患者之间的差异,并基于这些生物标志物开发一种新型诊断模型。
本研究纳入了341名参与者,包括246名MASLD患者(118名非肥胖患者,128名肥胖患者)和95名健康对照者。采用酶联免疫吸附测定法(ELISA)测量血清AGEs和esRAGE水平。使用套索算法确定关键预测因子,并通过逻辑回归建立诊断模型并以列线图形式可视化。通过曲线下面积(AUC)、自抽样验证、校准曲线和决策曲线分析(DCA)评估诊断准确性和实用性。
与对照组相比,MASLD患者的血清AGEs和esRAGE水平显著更高。此外,肥胖的MASLD患者的esRAGE水平高于非肥胖患者,但AGEs水平未发现显著差异。纳入年龄、腰围、体重指数、谷丙转氨酶、甘油三酯、高密度脂蛋白、AGEs和esRAGE的诊断模型的AUC为0.963,敏感性为94.3%,特异性为85.3%。自抽样内部验证的AUC为0.963(95%CI:0.944-0.982)。校准曲线显示出强大的预测准确性,DCA显示出较高的净临床效益。
血清AGEs和esRAGE可作为区分MASLD患者的非侵入性生物标志物。我们开发并验证了MASLD的诊断模型,为识别高危人群以及改进预防和治疗策略提供了有价值的工具。