UHPLC-MS/MS-Based Metabolomics and Clinical Phenotypes Analysis Reveal Broad-Scale Perturbations in Early Pregnancy Related to Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy, with adverse effects on both mother and fetus. The establishment of early diagnosis and risk assessment model is of great significance for preventing and reducing adverse outcomes of GDM. In this study, the broad-scale perturbations related to GDM were explored through the integration analysis of metabolic and clinical phenotypes. Maternal serum samples from the first trimester were collected for targeted metabolomics analysis by using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Statistical analysis was conducted based on the levels of the 184 metabolites and 76 clinical indicators from GDM women ( n =60) and matched healthy controls ( n =90). Metabolomics analysis revealed the down-regulation of fatty acid oxidation in the first trimester of GDM women, which was supposed to be related to the low serum level of dehydroepiandrosterone.While the significantly altered clinical phenotypes were mainly related to the increased risk of cardiovascular disease, abnormal iron metabolism, and inflammation. A phenotype panel established from the significantly changed serum indicators can be used for the early prediction of GDM, with the area under the receiver-operating characteristic curve (ROC) 0.83. High serum uric acid and C-reaction protein levels were risk factors for GDM independent of body mass indexes, with ORs 4.76 (95% CI: 2.08-10.90) and 3.10 (95% CI: 1.38-6.96), respectively. Predictive phenotype panel of GDM, together with the risk factors of GDM, will provide novel perspectives for the early clinical warning and diagnosis of GDM.

New perspective on first-trimester serum uric acid level in predicting the risk of gestational diabetes mellitus

“…Recently, the predictive abilities of 36 metabolites and 22 clinical indicators on the risk of GDM in the first trimester of pregnancy were analyzed 21 . The predictive potential of these serum phenotypes for GDM was as follows: eight phenotypes with an AUC > 0.68, including UA AUC of 0.71 and prepregnancy BMI AUC of up to 0.72.…”

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review

“…As a final note on the issue of GDM diagnosis, researchers have observed disturbances in purine degradation, in metabolites involved in insulin resistance, and fatty acid oxidation have been noted. Hu et al proposed an optimal GDM prediction model composed of glucose, uric acid, DL 11:0-iso2, L-phenylalanine, and direct bilirubin levels measured by UHPLC-MS/MS in the first trimester of pregnancy [ 217 ]. Similar alterations in metabolic pathways, including pyrimidine/purine derivatives involved in uric acid metabolism, carboxylic acids, fatty acylcarnitines, and SM in women at risk of GDM in the first trimester were noted by McMichael et al [ 218 ].…”