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

Abstract

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 if 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 centiles 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 (pre-specified) Neonatal birth centile and abdominal circumference. Methods Lipidomic profiling in the fasting plasma OGTT sample using direct infusion mass spectrometry. Analysis included logistic/ linear regression, unadjusted and adjusted for maternal age, BMI, 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 centile 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.

Insulin Resistance Is Associated with an Unfavorable Serum Lipoprotein Lipid Profile in Women with Newly Diagnosed Gestational Diabetes

“…The associations between insulin resistance and serum metabolome have been characterized previously outside pregnancy, but to extrapolate these findings into a pregnant population has several pitfalls. In addition, previous studies involving pregnant subjects have been scarce [ 15 , 16 , 17 , 18 ], and to our best knowledge the associations between maternal insulin resistance in GDM and detailed lipoprotein lipid profile have not previously been studied.…”

“…Of these metabolites, lipids and amino acids have previously been shown to associate with fetal growth [ 12 , 13 , 14 ] and duration of gestation [ 12 ]. The associations between maternal insulin resistance and metabolome have previously been studied in the HAPO [ 15 , 16 ] and UPBEAT [ 17 ] cohorts as well as at least one smaller prospective cohort [ 18 ], but the effects of maternal insulin resistance on lipids in different lipoprotein subfractions are not known. To develop more effective and individualized treatments for GDM, the pathophysiology, also regarding hyperlipidemia and amino-acidemia, needs to be more thoroughly understood.…”

Mechanisms mediating the impact of maternal obesity on offspring hypothalamic development and later function

“…Maternal obesity is however associated with an increase in maternal lipid levels, higher triglycerides and VLDL, and lower HDL-C than observed in lean women ( 105 ). GDM in women with obesity is associated with elevated plasma concentrations of a specific series of triglycerides consistent with increased de novo lipogenesis ( 106 ). Several recent studies indicate that maternal post-prandial triglycerides and free fatty acids are a stronger predictor of newborn adiposity and birth weight than maternal glucose in an obese pregnancy ( 106 , 107 ).…”

Differences in lipid metabolism in acquired versus preexisting glucose intolerance during gestation: role of free fatty acids and sphingosine-1-phosphate

“…There is evidence that differences in the onset of IGT manifestation and thus also in the pathophysiology GDM subtypes exists and the relationship between lipid metabolism and GDM has become stronger recently. In the prospective cohort from the UPBEAT trial GDM in obese patients was linked to elevated plasma diglycerides, TG and FFA concentrations, consistent with de novo lipogenesis [ 32 ]. These alterations could even be associated with neonatal abdominal circumference.…”