Predictive Gestational Diabetes Biomarkers With Sustained Alterations Throughout Pregnancy

Abstract

Gestational diabetes mellitus (GDM) results in an increased risk of pre- and postpartum health complications for both the mother and child. Metabolomics analysis can potentially identify predictive biomarkers and provide insight into metabolic alterations associated with GDM pathogenesis and progression, but few metabolomics studies investigate alterations observed across the first and third trimester. We hypothesize that metabolites altered in first trimester GDM that remain altered in late pregnancy may best inform interventions. Metabolomic studies comparing plasma and serum metabolite alterations in GDM vs non-GDM pregnancies were retrieved by searching PubMed, Medline, and CINAHL Plus databases. The present scoping review summarizes the metabolites found to be consistently altered throughout the course of GDM and proposes mechanisms that explain how these metabolic perturbations relate to GDM development and progression. Metabolites involved in fatty acid metabolism, reductive carboxylation, branched chain amino acids metabolism, cell membrane lipid metabolism, purine degradation, and the gut microbiome were found to be altered throughout GDM pregnancies, with many of these pathways showing mechanistic links to insulin resistance, inflammation, and impaired cell signaling. Future studies are required to investigate if normalization of these perturbed pathways can be the targets of interventions.

Depiction of Branched-Chain Amino Acids (BCAAs) in Diabetes with a Focus on Diabetic Microvascular Complications

“…Also, patients with GDM who follow metformin treatment present a higher rate of dysregulated BCAA metabolism compared with patients who follow insulin therapy [ 26 ]. Because weight loss with caloric restriction and reduced BCAA intake are prohibited in pregnancies, a persistent elevation of BCAAs in GDM patients leads to dysregulated energy metabolism and is highly predictive for GDM to T2DM transition [ 27 ].…”