Gestational Diabetes Is Characterized by Decreased Medium-Chain Acylcarnitines and Elevated Purine Degradation Metabolites across Pregnancy: A Case-Control Time-Course Analysis.

Gestational Diabetes Mellitus (GDM) results in complications affecting both mothers and their offspring. Metabolomic analysis across pregnancy provides an opportunity to better understand GDM pathophysiology. The objective was to conduct a metabolomics analysis of first and third trimester plasma samples to identify metabolic differences associated with GDM development. Forty pregnant women with overweight/obesity from a multisite clinical trial of a lifestyle intervention were included. Participants who developed GDM (n = 20; GDM group) were matched with those who did not develop GDM (n = 20; Non-GDM group). Plasma samples collected at the first (10-16 weeks) and third (28-35 weeks) trimesters were analyzed with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Cardiometabolic risk markers, dietary recalls, and physical activity metrics were also assessed. Four medium-chain acylcarnitines, lauroyl-, octanoyl-, decanoyl-, and decenoylcarnitine, significantly differed over the course of pregnancy in the GDM vs Non-GDM group in a group-by-time interaction (p < 0.05). Hypoxanthine and inosine monophosphate were elevated in the GDM group (p < 0.04). In both groups over time, bile acids and sorbitol increased while numerous acylcarnitines and α-hydroxybutyrate decreased (p < 0.05). Metabolites involved in fatty acid oxidation and purine degradation were altered across the first and third trimesters of GDM-affected pregnancies, providing insight into metabolites and metabolic pathways altered with GDM development.

Identification of potential biomarkers and metabolic insights for gestational diabetes prevention: A review of evidence contrasting gestational diabetes versus weight loss studies that may direct future nutritional metabolomics studies.

Gestational diabetes mellitus (GDM) significantly increases maternal health risks and adverse effects for the offspring. Observational studies suggest that weight loss before pregnancy may be a promising GDM prevention method. Still, biochemical pathways linking preconception weight changes with subsequent development of GDM among women who are overweight or obese remain unclear. Metabolomic assessment is a powerful approach for understanding the global biochemical pathways linking preconception weight changes and subsequent GDM. We hypothesize that many of the alterations of metabolite levels associated with GDM will change in one direction in GDM studies but will change in the opposite direction in studies focusing on lifestyle interventions for weight loss. The present review summarizes available evidence from 21 studies comparing women with GDM with healthy participants and 12 intervention studies that investigated metabolite changes that occurred during weight loss using caloric restriction and behavioral interventions. We discuss 15 metabolites, including amino acids, lipids, amines, carbohydrates, and carbohydrate derivatives. Of particular note are the altered levels of branched-chain amino acids, alanine, palmitoleic acid, lysophosphatidylcholine 18:1, and hypoxanthine because of their mechanistic links to insulin resistance and weight change. Mechanisms that may explain how these metabolite modifications contribute to GDM development in those who are overweight or obese are proposed, including insulin resistance pathways. Future nutritional metabolomics preconception intervention studies in overweight or obese are necessary to investigate whether weight loss through lifestyle intervention can reduce GDM occurrence in association with these metabolite alterations and to test the value of these metabolites as potential diagnostic biomarkers of GDM development.

Multiassay nutritional metabolomics profiling of low vitamin A status versus adequacy is characterized by reduced plasma lipid mediators among lactating women in the Philippines: A pilot study.

Low vitamin A (VA) status is common among lactating women in low-income countries. Lactation has substantial effects on mother's metabolism and VA is required in multiple biological processes, including growth, vision, immunity, and reproduction. The objective of this pilot study was to use metabolomics profiling to conduct a broad, exploratory assessment of differences in plasma metabolites associated with low VA status versus VA adequacy in lactating women. Plasma samples from lactating women who participated in a survey in Samar, Philippines, were selected from a cross-sectional study based on plasma retinol concentrations indicating low (VA-; n = 5) or adequate (VA+; n = 5) VA status (plasma retinol <0.8 or >1.05 µmol/L). The plasma results collected from 6 metabolomics assays (oxylipins, endocannabinoids, bile acids, primary metabolomics, biogenic amines, and lipidomics) were compared by group using liquid chromatography mass spectrometry. Twenty-eight metabolites were altered in the VA- versus VA+ status groups, with 24 being lipid mediators (P < .05). These lipid mediators included lower concentrations of arachidonic acid- and eicosapentaenoic acid-derived oxylipins, as well as lysophospholipids and sphingolipids, in the VA- group (P < .05). Chemical similarity enrichment analysis identified hydroxy-eicosatetraenoic acids, hydroxy-eicosapentaenoic acids, and dihydroxy-eicosatetraenoic acids as significantly altered oxylipin clusters (P < .0001, false discovery rate [FDR] P < .0001), as well as sphingomyelins, saturated lysophosphatidylcholines, phosphatidylcholines, and phosphatidylethanolamines (P < .001, FDR P < .01). The multiassay nutritional metabolomics profiling of low VA status compared with adequacy in lactating women was characterized by reduced lipid mediator concentrations. Future studies with stronger study designs and larger sample size are needed to confirm and validate these preliminary results.