The application of metabolomics analysis in the research of gestational diabetes mellitus and preeclampsia

Abstract

Aim The aim of the study was to investigate the difference of the serum metabolic profile between gestational diabetes mellitus (GDM) patients and preeclampsia (PE) patients, to establish the disease differentiation model and to find characteristic metabolites, in order to provide a new idea for the occurrence, development and treatment of the disease. Methods Twenty‐nine patients with GDM group and 29 PE group who were examined in Tianjin No. 3 Central Hospital from March 2018 to August 2018 were enrolled as case group, and 29 normal pregnant women were selected as control group. All the serum samples were analyzed by using the ultra‐performance liquid chromatography and mass spectrometry. Based on the multivariate statistical analysis method of pattern recognition, we screened out and identified the differential characteristic metabolites. Results The serum metabolic profile model of GDM group and PE group was successfully constructed. A total of nine characteristic metabolites were screened and identified in this study, including LPC 18:0, LPC 22:6, LPC 16:0, (S)‐14‐methylhexadecanoic acid, behenic acid, palmitic acid, sphingosine, phytosphingosine and 1,25‐dihydroxyvitamin D3‐26,23‐lactone. Among them, six characteristic metabolites which were LPC 18:0, LPC 22:6, behenic acid, palmitic acid, sphingosine and 1,25‐dihydroxyvitamin D3‐26,23‐lactone all had a significant statistical difference among GDM, PE and normal pregnancy groups (P < 0.05). Conclusion The construction of metabolic profile discriminant model has a strong ability to differentiate GDM patients from PE pregnant women. The screened characteristic metabolites can early reflect the disorder of lipid, calcium and phosphorus metabolism of patients, and provide reference and help for the discussion of the occurrence, development and treatment of diseases.

Serum and Amniotic Fluid Metabolic Profile Changes in Response to Gestational Diabetes Mellitus and the Association with Maternal–Fetal Outcomes

“…In serum from GDM, we found an increased level of L-palmitoylcarnitine, which was in line with Zhao's report that the levels of long-chain acylcarnitines were greater in GDM women in both the first and second trimesters [14]. L-Palmitoylcarnitine is an intermediate product of fatty acid oxidation, and its accumulation indicates the emergency of fatty acid peroxidation, which adversely affects insulin secretion [9]. Accordingly, a significantly positive correlation between L-palmitoylcarnitine and maternal FPG was found.…”

“…Valine, a BCAA reported to be correlated with insulin resistance and higher risk of diabetes and obesity, presented an increased expression in our study. It was also reported that the levels of BCAAs and ornithine were increased in cord blood of GDM women [9]. Moreover, the metabolites related to tryptophan, histidine, cysteine, and methionine metabolism played a certain role in the regulation of fetal body weight and CRL, which was also observed in Kadakia's study [28].…”

“…Pregnant women with GDM typically exhibit increased insulin resistance and reduced insulin secretion, which bring about a succession of abnormal metabolisms that are embodied directly by the aberrant expression of corresponding metabolites. Detecting metabolite profiles of GDM and identifying potential disease-related metabolic pathways will promote the understanding of GDM pathogenesis and ultimately achieve effective prevention and treatment [9]. Additionally, the fetus is directly exposed to AF, which is influenced by GDM [10], so identifying the differential AF metabolites and relevant metabolic pathways involved in the changed intrauterine environment will facilitate the understanding of the mechanism by which GDM has adverse effects on offspring.…”

Unique Biomarker Characteristics in Gestational Diabetes Mellitus Identified by LC-MS-Based Metabolic Profiling

“…Several studies have already identified early diagnostic markers and explored the pathophysiology of GDM using metabolomics. It has been reported that circulating fatty acids levels, including palmitic acid, stearic acid, and palmitoleic acid, were increased in GDM patients as compared with normal pregnancy groups [19][20][21][22][23]. Additional metabolites were also found to be significantly increased in women with GDM, such as prostanoic acid, sesaminol 2-O-triglucoside, tricin 7-neohesperidoside, dihydro-12-oxo-15-phytoenoic acid [24], acetylcarnitines [21,22], bile acids [25], ketones [21,26], creatinine, carbohydrate (primary glucose) [26], and other lipids and organic acids.…”

Placental metabolic profiling in gestational diabetes mellitus: An important role of fatty acids

“…Insulin resistance, low‐grade inflammation, and endothelial cell dysfunction are considered its characteristic features. Increasing studies highlight the importance of metabolite alterations in GDM, and most efforts are focused on investigating biomarkers that could facilitate prediction and diagnosis 17–19 . These studies suggested that changes in maternal metabolic status tend to affect the levels of various metabolites and metabolic homeostasis in the fetus and subsequently lead to an increased complication of pregnancy, such as macrosomia.…”