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 Gestational Diabetes Mellitus (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.

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 αhydroxybutyrate 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.

Objectives Gestational Diabetes Mellitus (GDM) is present in up to 10% of pregnancies in the United States. The occurrence of GDM causes severe short- and long-term complications for the mother and offspring. baby pre- and post-partum. Identification of the metabolites and potential biomarkers involved in GDM could improve the prediction of its occurence. The integration of food data with metabolite results could provide innovative diet intervention strategies. The objective of this study is to identify metabolites that differed in the first and third trimesters of GDM versus Non-GDM pregnancies. Methods Participants were 68 OW/OB pregnant women enrolled in the Healthy Beginnings Trial and completed blood draws at first (10–16 weeks) and third trimester (28–35 weeks).  Participants from the control and dietary intervention group who developed GDM (n = 34; GDM group) were matched on age, BMI, ethnicity, and treatment group with those who did not develop GDM (n = 34; Non-GDM group). Plasma samples were analyzed by ultra-high-performance liquid chromatography-hybrid triple-quadrupole linear ion trap mass spectrometry (UPLC-QTRAP) using three targeted metabolomics assays for primary metabolomics, aminomics and lipdomics. Dietary intake was estimated using 24 hour recalls in order to assess potential dietary differences between groups. Results A total of 243 metabolites were identified in the plasma samples. At first trimester, several complex lipids, including cholestryl esters and phospholipids, were higher in the GDM group (P &lt; 0.05). Furthermore, the purine derivative hypoxanthine was also higher in GDM subjects (P &lt; 0.05). At third trimester, multiple acylcarnitines, associated with utilization of fat for energy, were lower in the GDM group (P &lt; 0.05). Conclusions Metabolite differences between GDM and Non-GDM groups in plasma samples collected during first trimester may predict the development of GDM. Further research is required to identify the roles these metabolite changes play in the development of this disease. Funding Sources NIH National Heart, Lung, and Blood Institute (NHLBI; HL114377), ARI #58,875, Cal Poly CAFES SURP.

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