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 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 acid 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.

Keywords: branched-chain amino acids; fatty acid metabolism; gestational diabetes mellitus; metabolomics; purine degradation; reductive carboxylation.

Figure 1.

Study and metabolite search flowchart.

Figure 2.

A summary of metabolites and pathways found to be altered across pregnancy in GDM metabolomic studies. Pathways observed to be dysregulated across pregnancy in GDM metabolomics studies include fatty acid metabolism, BCAA metabolism, reductive carboxylation, and cell membrane lipid metabolism. Figure created in BioRender.com. FA, fatty acid; FAO, fatty acid oxidation; FFA, free fatty acids; BCAA, branched-chain amino acid; LPC, lysophosphatidylcholine; PC, phosphatidylcholine; SM, sphingomyelins.

Figure 3.

Fatty acid metabolism and reductive carboxylation metabolites observed to be altered throughout GDM-affected pregnancies. Upward arrows indicate an increase in the metabolite in GDM compared with non-GDM pregnancies while downward arrows indicate a decrease.

Figure 4.

Cell membrane lipid metabolites observed to be altered throughout GDM-affected pregnancies. Upward arrows indicate an increase in the metabolite in GDM compared to non-GDM pregnancies while downward arrows indicate a decrease.