1344-P: Metabolomics Reveals Broad Scale Metabolic Changes in Gestational Diabetes

Studies examining metabolites in GDM have been small with inconsistent results. To address this, we used targeted metabolomics to examine levels of 65 metabolites in a cohort of 3457 mothers from the Hyperglycemia and Adverse Pregnancy Outcome Study, of whom 547 were retrospectively diagnosed with GDM using IADPSG criteria. GDM was untreated. Metabolomics assays were performed on fasting and 1 hr serum samples collected during an oral glucose tolerance test (OGTT) at ∼28 weeks gestation. Differences in metabolite levels in women without and with GDM were determined using linear regression with adjustment for field center as well as maternal age, gestational age, height, mean arterial pressure, parity, smoking (yes/no), drinking (yes/no) and BMI at the OGTT and false discovery rate correction. Women with GDM had higher levels of a broad array of fasting metabolites, including branched chain amino acids (BCAA) and their metabolic byproducts, aromatic and other amino acids, triglycerides, non-esterified fatty acids and lipid byproducts, and medium- and long-chain acylcarnitines (ACs). Similar differences were seen 1 hr after a glucose load, except for higher levels of a broader array of ACs but lower levels of arachidonoyl carnitine in women with GDM. Prior studies categorizing women with GDM into those with normal and low insulin sensitivity demonstrated differences in maternal and newborn outcomes between groups. Compared to women with GDM and normal insulin sensitivity, women with GDM in the lowest quartile of insulin sensitivity had higher levels of BCAAs and their metabolic byproducts, aromatic amino acids, triglycerides, and lactate but lower levels of 3-hydroxybutyrate (3-HB) and multiple ACs. A generally a similar pattern was seen 1 hr after glucose except for no change in 3-HB. Together these data demonstrate broad scale perturbations in metabolites in women with GDM and differences across subgroups of women with GDM that may contribute to maternal and fetal complications related to GDM.