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.