Metabolic profiling of gestational diabetes in obese women during pregnancy

Abstract

Aims/hypothesis: Antenatal 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.

Methods: We 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.

Results: Multiple 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/interpretation: Among 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.

Keywords: Biomarkers; Gestational diabetes; Lipids; Obesity; Pregnancy; Targeted metabolome.

Fig. 1

Differences in lipoprotein particle groups between GDM and non-GDM women at time points 1 and 2. Total lipids in all lipoprotein subclasses, particle size, apolipoproteins and total lipoprotein constituents were measured at time points 1 and 2. Data points show the SD difference between GDM and non-GDM women prior to diagnosis of GDM (time point 1) and at the time of OGTT (time point 2). Positive associations with GDM are shown to the right, negative associations are shown to the left. Closed black circles represent FDR-corrected p values of <0.05. Free cholesterol, non-esterified cholesterol; PC, phosphatidylcholines; PG, phosphoglycerides; SM, sphingomyelins; TG:PG, triacylglycerol:phosphoglyceride

Fig. 2

Differences in lipoprotein subclass constituents between GDM and non-GDM women at time points 1 and 2. Lipoprotein subclass constituent contents were measured at time points 1 and 2. Data points show the SD difference between GDM and non-GDM women prior to diagnosis of GDM (time point 1) and at the time of OGTT (time point 2). Positive associations with GDM are shown to the right, negative associations are shown to the left. Closed black circles represent FDR-corrected p values of <0.05. Free cholesterol, non-esterified cholesterol

Fig. 3

Differences in fatty acids, amino acids, glycaemic and other markers between GDM and non-GDM women at time points 1 and 2. Fatty acids, glycolysis-related metabolites, amino acids, ketone bodies and inflammatory and other markers were measured at time points 1 and 2. Data points show the SD difference between GDM and non-GDM women prior to diagnosis of GDM (time point 1) and at the time of  OGTT (time point 2). Positive associations with GDM are shown to the right, negative associations are shown to the left. Closed black circles represent FDR-corrected p values of <0.05. DHA, docosahexaenoic acid, 22:6; LA, linoleic acid, 18:2; MUFA monounsaturated fatty acids, 16:1, 18:1; PUFA polyunsaturated fatty acids; SFA Saturated fatty acids; TFA, total fatty acids