Wu Tao, Yang Ming, Xu Hanchen, Wang Lei, Wei Huafeng, Ji Guang
Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, South Wanping Road 725, Shanghai 200032, China.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Cailun Road 1200, Shanghai 201203, China.
J Proteome Res. 2021 Aug 6;20(8):3814-3825. doi: 10.1021/acs.jproteome.1c00104. Epub 2021 May 27.
The present study aimed to assess the ability of serum bile acid profiles to predict the development of nonalcoholic fatty liver (NAFL) in type 2 diabetes mellitus (T2DM) patients. Using targeted ultraperformance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry (TQ/MS), we compared serum bile acid levels in T2DM patients with NAFL ( = 30) and age- and sex-matched T2DM patients without NAFL ( = 36) at the first time. Second, an independent cohort study of T2DM patients with NAFL ( = 17) and age- and sex-matched T2DM patients without NAFL ( = 20) was used to validate the results. The incremental benefits of serum biomarkers, clinical variables alone, or with biomarkers were then evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. The area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to evaluate the biomarker predictive abilities. The serum bile acid profiles in T2DM patients with NAFL were significantly different from T2DM patients without NAFL, as characterized by the significant elevation of LCA, TLCA, TUDCA, CDCA-24G, and TCDCA, which may be potential biomarkers for the identification of NAFL in T2DM patients. Based on the improvement in AUC, IDI, and NRI, the addition of 5 bile acids to a model with clinical variables statistically improved its predictive value. Similar results were found in the validation cohort. These results highlight that the detected biomarkers may contribute to the progression of NAFL in T2DM patients, and these biomarkers particularly in combination may help in the diagnosis of NAFL and allow earlier intervention in T2DM patients.
本研究旨在评估血清胆汁酸谱预测2型糖尿病(T2DM)患者非酒精性脂肪肝(NAFL)发生发展的能力。我们首次使用靶向超高效液相色谱(UPLC)结合三重四极杆质谱(TQ/MS),比较了30例患有NAFL的T2DM患者和36例年龄及性别匹配的无NAFL的T2DM患者的血清胆汁酸水平。其次,我们利用一项针对17例患有NAFL的T2DM患者和20例年龄及性别匹配的无NAFL的T2DM患者的独立队列研究来验证结果。然后,使用受试者工作特征(ROC)曲线和决策曲线分析评估血清生物标志物、单独的临床变量或两者结合的增量益处。曲线下面积(AUC)、综合判别改善(IDI)和净重新分类改善(NRI)用于评估生物标志物的预测能力。患有NAFL的T2DM患者的血清胆汁酸谱与无NAFL的T2DM患者显著不同,其特征为LCA、TLCA、TUDCA、CDCA - 24G和TCDCA显著升高,这些可能是T2DM患者中NAFL的潜在生物标志物。基于AUC、IDI和NRI的改善情况,在包含临床变量的模型中加入5种胆汁酸在统计学上提高了其预测价值。在验证队列中也发现了类似结果。这些结果表明,检测到的生物标志物可能与T2DM患者中NAFL的进展有关,尤其是这些生物标志物联合使用可能有助于NAFL的诊断,并能在T2DM患者中实现更早的干预。