Altered Lipid Metabolism in Obese Women With Gestational Diabetes and Associations With Offspring Adiposity

Context Gestational diabetes (GDM) affects 20 million women/year worldwide and is associated with childhood obesity. Infants of affected mothers have increased adiposity from birth, which leads to obesity in later life. However, it remains unknown whether the effect of GDM upon neonatal body composition is due to hyperglycemia alone or is mediated by other pathways. Objective To investigate plasma lipid profiles in obese women according to GDM diagnosis, infant birthweight percentiles, and adiposity. Design Prospective cohort from UPBEAT trial (ISRCTN 89971375). Setting Hospital and community. Patients 867 obese pregnant women recruited in early pregnancy, assessed at 28 weeks for GDM. Offspring anthropometry was assessed at birth. Outcome (Prespecified) Neonatal birth percentile and abdominal circumference. Methods Lipidomic profiling in the fasting plasma oral glucose tolerance test sample using direct infusion mass spectrometry. Analysis included logistic/linear regression, unadjusted and adjusted for maternal age, body mass index, parity, ethnicity, UPBEAT trial arm, and fetal sex. The limit of significance was P = 0.05 for offspring anthropometry and P = 0.002 for lipidomic data. Results GDM in obese women was associated with elevated plasma concentrations of specific diglycerides [DG(32:0)] and triglycerides [TG(48:0), (50:1), (50:2)] containing fatty acids (16:0), (16:1), (18:0), and (18:1), consistent with increased de novo lipogenesis. In the whole cohort, these species were associated with birthweight percentile and neonatal abdominal circumference. Effects upon infant abdominal circumference remained significant after adjustment for maternal glycemia. Conclusions Increased de novo lipogenesis-related species in pregnant women with obesity and GDM are associated with measures of offspring adiposity and may be a target for improving lifelong health.