Distinct Metabolomic Profile Because of Gestational Diabetes and its Treatment Mode in Women with Overweight and Obesity

Abstract

Objective Whether the presence of gestational diabetes (GDM) and its treatment mode influence the serum metabolic profile in women with overweight or obesity was studied. Methods The serum metabolic profiles of 352 women with overweight or obesity participating in a mother‐infant clinical study were analyzed with a targeted NMR approach (at 35.1 median gestational weeks). GDM was diagnosed with a 2‐hour 75‐g oral glucose tolerance test. Results The metabolomic profile of the women with GDM (n = 100) deviated from that of women without GDM (n = 252). Differences were seen in 70 lipid variables, particularly higher concentrations of very low‐density lipoprotein particles and serum triglycerides were related to GDM. Furthermore, levels of branched‐chain amino acids and glycoprotein acetylation, a marker of low‐grade inflammation, were higher in women with GDM. Compared with women with GDM treated with diet only, the women treated with medication (n = 19) had higher concentrations of severalizes of VLDL particles and their components, leucine, and isoleucine, as well as glycoprotein acetylation. Conclusions A clearly distinct metabolic profile was detected in GDM, which deviated even more if the patient was receiving medical treatment. This suggests a need for more intense follow‐up and therapy for women with GDM during pregnancy and postpartum to reduce their long‐term adverse health risks.

Current progress in metabolomics of gestational diabetes mellitus

“…In addition to perturbations in hexose metabolism, some disorders of glucose metabolism pathway molecules have also been detected in women with GDM. Mokkala et al [ 50 ] found that the level of citrate, which is an intermediate in the tricarboxylic acid cycle synthesized from acetyl-CoA and oxaloacetate, increased in women with GDM. Citric acid inhibits glycolysis and conversely stimulates gluconeogenesis and lipid synthesis, i.e.…”

“…β-hydroxybutyric acid is a classic ketone body found alongside acetone and acetoacetate. Mokkala et al [ 50 ] also found elevated levels of the ketone body acetoacetate in patients with gestational diabetes. Previous studies have also detected increased concentrations of ketone bodies in pregnant women with high fasting blood glucose levels[ 66 ] and found that they are associated with GDM[ 67 - 69 ].…”

“…Even after drug treatment, there were still differences in lipid composition and particle size among the three groups at 34-36 wk of gestation. In recent years, Mokkala et al [ 50 ] found no differences in lipids in VLDL, and very large and large HDL particles were detected in overweight or obese women who had been treated for GDM for approximately 10 wk. Variations among these results may be due to the inconsistency in population selection, sampling times, and the improvement in metabolic variables to a certain extent by treatment[ 67 , 145 ].…”

Associations of Dietary Bioactive Compounds with Maternal Adiposity and Inflammation in Gestational Diabetes: An Update on Observational and Clinical Studies

“…Metabolomics research is attempting to characterize the metabolic profile of women with GDM compared to women without the disease and how treatment modality affects the profile. In a recent report (2020), levels of certain lipid, amino acid, and acetylated glycoprotein metabolites were shown to be greater in women with overweight or obesity and GDM and to be contingent on treatment type (diet alone vs. medication) [92]. Ascertaining the metabolic profiles of women at risk for or diagnosed with overt GDM will further shape precision medicine in which complex metabolic profiles are used to correctly identify at-risk women, aid in diagnosis, predict the efficacy of therapies, and individualize treatment.…”

Impact of combined consumption of fish oil and probiotics on the serum metabolome in pregnant women with overweight or obesity

“…Thus, our first aim was to investigate the effects of supplementing diet with probiotics and fish oil, either separately or in combination, compared to placebo, to modify serum metabolites, as analysed using metabolomics over the course of pregnancy in pregnant women with overweight or obesity. Secondly, as the metabolic profile is disturbed in GDM [19], we investigated whether women with or without GDM would respond differentially to the intervention.…”