Abstract
Aims/hypothesisAntenatal obesity and associated gestational diabetes (GDM) are increasing worldwide. While pre-existing insulin resistance is implicated in GDM in obese women, the responsible metabolic pathways remain poorly described. Our aim was to compare metabolic profiles in blood of obese pregnant women with and without GDM 10 weeks prior to and at the time of diagnosis by OGTT.MethodsWe investigated 646 women, of whom 198 developed GDM, in this prospective cohort study, a secondary analysis of UK Pregnancies Better Eating and Activity Trial (UPBEAT), a multicentre randomised controlled trial of a complex lifestyle intervention in obese pregnant women. Multivariate regression analyses adjusted for multiple testing, and accounting for appropriate confounders including study intervention, were performed to compare obese women with GDM with obese non-GDM women. We measured 163 analytes in serum, plasma or whole blood, including 147 from a targeted NMR metabolome, at time point 1 (mean gestational age 17 weeks 0 days) and time point 2 (mean gestational age 27 weeks 5 days, at time of OGTT) and compared them between groups.ResultsMultiple significant differences were observed in women who developed GDM compared with women without GDM (false discovery rate corrected p values <0.05). Most were evident prior to diagnosis. Women with GDM demonstrated raised lipids and lipoprotein constituents in VLDL subclasses, greater triacylglycerol enrichment across lipoprotein particles, higher branched-chain and aromatic amino acids and different fatty acid, ketone body, adipokine, liver and inflammatory marker profiles compared with those without GDM.Conclusions/interpretationAmong obese pregnant women, differences in metabolic profile, including exaggerated dyslipidaemia, are evident at least 10 weeks prior to a diagnosis of GDM in the late second trimester.
Highlights
Pregnancy is associated with profound changes in metabolism, which facilitate the growth of a healthy fetus and prepare the mother and infant for the energy requirements in the postpartum period
Two recent metabolomic studies of normal pregnancy have described widespread metabolic perturbations that extend beyond the traditional boundaries of insulin resistance to encompass pathways including amino acids, lipoproteins and inflammatory markers [3, 4]
We found that an algorithm including clinical factors and some conventionally measured biomarkers analysed early in the second trimester of pregnancy performed well, the addition of more complicated metabolomic measures did not augment the performance of the tool [10]
Summary
Pregnancy is associated with profound changes in metabolism, which facilitate the growth of a healthy fetus and prepare the mother and infant for the energy requirements in the postpartum period. While the metabolic response to pregnancy is recognised to be different in this increasingly prevalent subgroup of the antenatal population [1], the pathways to GDM in obese women remain poorly described. This is of importance as less than one-third of obese women develop GDM. Two recent metabolomic studies of normal pregnancy have described widespread metabolic perturbations that extend beyond the traditional boundaries of insulin resistance to encompass pathways including amino acids, lipoproteins and inflammatory markers [3, 4]. None has addressed the metabolome in obese women prior to and at the time of GDM diagnosis
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