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

Prediction of Gestational Diabetes through NMR Metabolomics of Maternal Blood.

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†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.
§Maternidade Bissaya Barreto, Centro Hospitalar e Universitário de Coimbra - CHUC, 3000 Coimbra, Portugal.
∥Cytogenetics and Genomics Laboratory, Faculty of Medicine, and CNC.IBILI, University of Coimbra, Portugal and CIMAGO Center for Research in Environment, Genetics and Oncobiology, 3000 Coimbra, Portugal.


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.


NMR; gestational diabetes mellitus (GDM); lipid extracts; maternal plasma; metabolomics; prediagnosis GDM; pregnancy

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