Prediction of Gestational Diabetes through NMR Metabolomics of Maternal Blood

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.

Applications of metabolomics in the study and management of preeclampsia: a review of the literature

“…Blood plasma was the most commonly used biologic media (n = 10) (Bahado-Singh, Akolekar, Mandal, Dong, Xia, Kruger, Wishart et al 2012; De Oliveira, Câmara, Bonetti, Turco, Bertolla, Moron, Sass et al 2012; Kelly, Croteau-Chonka, Dahlin, Mirzakhani, Wu, Wan, McGeachie et al 2016; Kenny, Broadhurst, Dunn, Brown, North, McCowan, Roberts et al 2010; Kenny, Dunn, Ellis, Myers, Baker, Kell 2005; Odibo, Goetzinger, Odibo, Cahill, Macones, Nelson, Dietzen 2011; Pinto, Almeida, Martins, Duarte, Barros, Galhano, Pita et al 2015; Schott, Hahn, Kurbacher, Moka 2012; Turner, Brewster, Simpson, Walker, Fisher 2007; Turner, Brewster, Simpson, Walker, Fisher 2008), followed by serum (n = 7) (Bahado-Singh, Akolekar, Mandal, Dong, Xia, Kruger, Wishart et al 2013; Bahado-Singh, Syngelaki, Akolekar, Mandal, Bjondahl, Han, Dong et al 2015; Chen, He, Tan, Xu 2017; Kenny, Broadhurst, Brown, Dunn, Redman, Kell, Baker 2008; Koster, Vreeken, Harms, Dane, Kuc, Schielen, Hankemeier et al 2015; Kuc, Koster, Pennings, Hankemeier, Berger, Harms, Dane et al 2014), and placental or intrauterine tissue samples (n = 7) (Austdal, Thomsen, Tangerås, Skei, Mathew, Bjørge, Austgulen et al 2015; Baig, Lim, Fernandis, Wenk, Kale, Su, Biswas et al 2013; Dunn, Brown, Worton, Davies, Jones, Kell, Heazell 2012; Jain, Jayasimhulu, Clark 2004; Korkes, Sass, Moron, Câmara, Bonetti, Cerdeira, Da Silva et al 2014; Pearson, Zhang, Arya, Warren, Ortori, Fakis, Khan et al 2010; Sohlberg, Wikström, Olovsson, Lindgren, Axelsson, Mulic-Lutvica, Weis et al). The remaining studies used urine (n = 1) (Diaz, Barros, Goodfellow, Duarte, Galhano, Pita, Almeida et al 2013), urine and serum (n = 2) (Austdal, Skråstad, Gundersen, Austgulen, Iversen, Bathen 2014; Austdal, Tangerås, Skråstad, Salvesen, Austgulen, Iversen, Bathen 2015), or breast milk (n=1) (Dangat, Upadhyay, Kilari, Sharma, Kemse, Mehendale, Lalwani et al 2016).…”

What Have Metabolomics Approaches Taught Us About Type 2 Diabetes?

“…Not surprisingly, metabolomic analyses in GDM have identified signatures similar to other insulin resistant states, including elevations in NEFA and ketones (109–114). Elevations in FA, cholesterol, and lipoproteins may precede and predict GDM (115). Increased BCAA are identified in some GDM studies (110, 111), but not all, perhaps due to differences in timing of sample collection (116, 117).…”

Metabolic profiling of gestational diabetes in obese women during pregnancy

“…Two recent metabolomic studies of normal pregnancy have described widespread metabolic perturbations that extend beyond the traditional boundaries of insulin resistance to encompass pathways including amino acids, lipoproteins and inflammatory markers [3,4]. GDM has also been the focus of some recent metabolomic studies, although to date all have included participants from across the maternal weight spectrum, which is itself known to affect the maternal metabolome [5][6][7][8][9]. None has addressed the metabolome in obese women prior to and at the time of GDM diagnosis.…”