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.

Lifestyle Intervention in Danish Obese Pregnant Women With Early Gestational Diabetes Mellitus According to WHO 2013 Criteria Does Not Change Pregnancy Outcomes: Results From the LiP (Lifestyle in Pregnancy) Study

“…Other studies have also reported that women with early GDM by WHO 2013 criteria have phenotypic characteristics in common with the metabolic syndrome (24). The UPBEAT study demonstrated that differences in metabolic profile, including exaggerated dyslipidemia, were present at least 10 weeks prior to a diagnosis of GDM in the late second trimester (25). This information may help with identifying women at risk.…”

Metabolic phenotyping by treatment modality in obese women with gestational diabetes suggests diverse pathophysiology: An exploratory study

“…Analytes measured using conventional laboratory platforms (S1 Table) included glucose homeostasis markers, sex hormone binding globulin (SHBG), gamma glutamyl transferase (gGT) and adiponectin. For the purposes of this study and to restrict multiple comparisons, only those analytes identified previously as different between women with GDM and women without GDM at the time of diagnosis (time point 2) [7] were explored. A total of 89 analytes, 83 from the NMR metabolome, were evaluated.…”

“…We have previously shown that obese women with GDM have differing metabolic profiles from obese women without GDM and that this is evident prior to diagnosis [7]. Using the same dataset, we have hypothesised that the measured analytes might further distinguish between groups necessitating diverse treatment approaches to achieve glucose control.…”

Physical and Mental Health Consequences of Obesity in Women

“…One of the most common reproductive disorders in women of childbearing age, and the leading cause of infertility, is polycystic ovarian syndrome (PCOS), which can be impaired or even caused by visceral obesity [10]. Maternal health has been reported to worsen as a result of obesity or abnormal weight gain during pregnancy [11][12][13]. Obesity is related to early loss of pregnancy, higher rates of caesarean (c-) section and high-risk obstetrical conditions, in addition to higher maternal and neonatal mortality rates and congenital malformations [8,[14][15][16].…”