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.

Metabolites involved in purine degradation, insulin resistance, and fatty acid oxidation are associated with prediction of Gestational diabetes in plasma.

INTRODUCTION: Gestational diabetes mellitus (GDM) significantly increases maternal and fetal health risks, but factors predictive of GDM are poorly understood. OBJECTIVES: Plasma metabolomics analyses were conducted in early pregnancy to identify potential metabolites associated with prediction of GDM. METHODS: Sixty-eight pregnant women with overweight/obesity from a clinical trial of a lifestyle intervention were included. Participants who developed GDM (n = 34; GDM group) were matched on treatment group, age, body mass index, and ethnicity with those who did not develop GDM (n = 34; Non-GDM group). Blood draws were completed early in pregnancy (10-16 weeks). Plasma samples were analyzed by UPLC-MS using three metabolomics assays. RESULTS: One hundred thirty moieties were identified. Thirteen metabolites including pyrimidine/purine derivatives involved in uric acid metabolism, carboxylic acids, fatty acylcarnitines, and sphingomyelins (SM) were different when comparing the GDM vs. the Non-GDM groups (p < 0.05). The most significant differences were elevations in the metabolites' hypoxanthine, xanthine and alpha-hydroxybutyrate (p < 0.002, adjusted p < 0.02) in GDM patients. A panel consisting of four metabolites: SM 14:0, hypoxanthine, alpha-hydroxybutyrate, and xanthine presented the highest diagnostic accuracy with an AUC = 0.833 (95% CI: 0.572686-0.893946), classifying as a "very good panel". CONCLUSION: Plasma metabolites mainly involved in purine degradation, insulin resistance, and fatty acid oxidation, were altered in early pregnancy in connection with subsequent GDM development.