The effects of gestational diabetes mellitus with maternal age between 35 and 40 years on the metabolite profiles of plasma and urine

Abstract

Background Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. While there are limited metabolomic studies involving advanced maternal age in China, we aim to investigate the metabolomic profiling of plasma and urine in pregnancies complicated with GDM aged at 35–40 years at early and late gestation. Methods Twenty normal and 20 GDM pregnant participants (≥ 35 years old) were enlisted from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine collected at the first and third trimester were detected using gas chromatography-mass spectrometry (GC-MS). Results One hundred sixty-five metabolites and 192 metabolites were found in plasma and urine respectively. Urine metabolomic profiles were incapable to distinguish GDM from controls, in comparison, there were 14 and 39 significantly different plasma metabolites between the two groups in first and third trimester respectively. Especially, by integrating seven metabolites including cysteine, malonic acid, alanine, 11,14-eicosadienoic acid, stearic acid, arachidic acid, and 2-methyloctadecanoic acid using multivariant receiver operating characteristic models, we were capable of discriminating GDM from normal pregnancies with an area under curve of 0.928 at first trimester. Conclusion This study explores metabolomic profiles between GDM and normal pregnancies at the age of 35–40 years longitudinally. Several compounds have the potential to be biomarkers to predict GDM with advanced maternal age. Moreover, the discordant metabolome profiles between the two groups could be useful to understand the etiology of GDM with advanced maternal age.

Predictive Gestational Diabetes Biomarkers With Sustained Alterations Throughout Pregnancy

“…One postdiagnosis study observed a decrease in pyruvate [ 35 ]. Similarly, citrate was found to be higher in in 3 prediagnosis studies [ 15 , 21 , 22 ], 1 at-diagnosis study [ 21 ], and 1 postdiagnosis study [ 15 ] ( Table 1 ). Pyruvate and citrate have been implicated in glucose-stimulated insulin secretion, with pyruvate working to maintain high citrate levels via the reductive carboxylation pathway for the purpose of NADPH production, which supports insulin secretion [ 55 , 56 ] ( Fig.…”

“…In further support of dysregulated fatty acid metabolism is the observed alterations in alpha-hydroxybutyrate, a metabolite closely connected to FAO. Alpha-hydroxybutyrate was elevated in 1 prediagnosis [ 25 ], 3 at-diagnosis [ 23 , 26 , 28 ], and 1 postdiagnosis studies [ 15 ] ( Table 1 ). Alpha-hydroxybutyrate has been identified as a marker of the elevated ratio of cytosolic NADH/NAD + , as this metabolite is formed from alpha-ketobutyrate in a reaction that can be catalyzed by lactate dehydrogenase when the cytosolic NADH/NAD + ratio is increased [ 49 , 50 ] ( Fig.…”

“…BCAAs were upregulated across pregnancy in GDM studies, with leucine increasing in 5 prediagnosis [ 21 , 22 , 33 , 34 , 41 ] and 4 postdiagnosis studies [ 21 , 23 , 42 , 43 ], isoleucine increase in 4 prediagnosis [ 21 , 22 , 33 , 34 ] and 2 at-diagnosis studies [ 21 , 23 ], and valine increasing in 5 prediagnosis studies [ 21 , 22 , 27 , 33 , 35 ], 2 at-diagnosis studies [ 21 , 23 ], and 1 postdiagnosis study [ 15 ]. Both isoleucine and valine were found to decrease in 1 prediagnosis study [ 17 ], while valine also decreased in 1 at-diagnosis [ 44 ] and 1 postdiagnosis study [ 35 ] ( Table 1 ).…”

“…Another limitation of GDM metabolomics studies is lack of clarity regarding exclusion criteria. Of the 27 GDM metabolomics studies included in this review, 19 stated T1DM and T2DM as an exclusion criterion [ 21 , 22 , 24–28 , 32–34 , 36 , 39–41 , 43 , 44 , 45 , 88 , 125 ], while 8 did not explicitly state these forms of diabetes as an exclusion criterion [ 14 , 15 , 17 , 35 , 38 , 46–48 ]. Additionally, only 2 of these studies stated that pregestational diabetes was screened for during the study [ 44 , 125 ], while all others appeared to use self-reporting or medical history to determine T1DM and T2DM status.…”

Proteins and metabolites fingerprints of gestational diabetes mellitus forming protein–metabolite interactomes are its potential biomarkers

“…The first trimester of pregnancy also included an increased level of xanthine [115], nicotinamide, uridine [113], in the women who later developed GDM. Higher level of citric acid and beta‐alanine were found in the first trimester of GDM pregnancies [116]. Further, ethanolamine and 1,3‐diphosphoglycerate were found to be potential biomarkers of GDM during the first or early second trimester of pregnancy [117].…”