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通过母体血液的核磁共振代谢组学预测妊娠期糖尿病

Prediction of Gestational Diabetes through NMR Metabolomics of Maternal Blood.

作者信息

Pinto Joana, Almeida Lara M, Martins Ana S, Duarte Daniela, Barros António S, Galhano Eulália, Pita Cristina, Almeida Maria do Céu, Carreira Isabel M, Gil Ana M

机构信息

†CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

‡QOPNA Research Unit, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

出版信息

J Proteome Res. 2015 Jun 5;14(6):2696-706. doi: 10.1021/acs.jproteome.5b00260. Epub 2015 May 8.

Abstract

Metabolic biomarkers of pre- and postdiagnosis gestational diabetes mellitus (GDM) were sought, using nuclear magnetic resonance (NMR) metabolomics of maternal plasma and corresponding lipid extracts. Metabolite differences between controls and disease were identified through multivariate analysis of variable selected (1)H NMR spectra. For postdiagnosis GDM, partial least squares regression identified metabolites with higher dependence on normal gestational age evolution. Variable selection of NMR spectra produced good classification models for both pre- and postdiagnostic GDM. Prediagnosis GDM was accompanied by cholesterol increase and minor increases in lipoproteins (plasma), fatty acids, and triglycerides (extracts). Small metabolite changes comprised variations in glucose (up regulated), amino acids, betaine, urea, creatine, and metabolites related to gut microflora. Most changes were enhanced upon GDM diagnosis, in addition to newly observed changes in low-Mw compounds. GDM prediction seems possible exploiting multivariate profile changes rather than a set of univariate changes. Postdiagnosis GDM is successfully classified using a 26-resonance plasma biomarker. Plasma and extracts display comparable classification performance, the former enabling direct and more rapid analysis. Results and putative biochemical hypotheses require further confirmation in larger cohorts of distinct ethnicities.

摘要

利用母体血浆及相应脂质提取物的核磁共振(NMR)代谢组学方法,寻找妊娠糖尿病(GDM)诊断前后的代谢生物标志物。通过对选定变量的(1)H NMR光谱进行多变量分析,确定对照组与疾病组之间的代谢物差异。对于诊断后的GDM,偏最小二乘回归确定了对正常孕周演变依赖性更高的代谢物。NMR光谱的变量选择为诊断前和诊断后的GDM均产生了良好的分类模型。诊断前的GDM伴有胆固醇升高以及脂蛋白(血浆)、脂肪酸和甘油三酯(提取物)的轻微升高。较小的代谢物变化包括葡萄糖(上调)、氨基酸、甜菜碱、尿素、肌酸以及与肠道微生物群相关的代谢物的变化。除了新观察到的低分子量化合物变化外,大多数变化在GDM诊断后增强。利用多变量谱变化而非一组单变量变化似乎可以实现GDM预测。使用26重共振血浆生物标志物可成功对诊断后的GDM进行分类。血浆和提取物显示出可比的分类性能,前者能够进行直接且更快速的分析。结果和假定的生化假设需要在更大规模的不同种族队列中进一步证实。

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