Analysis of serum fatty acid, amino acid, and organic acid profiles in gestational hypertension and gestational diabetes mellitus via targeted metabolomics

Abstract

This study aimed to characterize metabolite differences and correlations between hypertensive disorders of pregnancy (HP) and gestational diabetes mellitus (GDM) using univariate, multivariate analyses, RF, and pathway analyses in a cross-sectional study. Dietary surveys were collected and targeted metabolomics was applied to measure levels of serum fatty acids, amino acids, and organic acids in 90 pregnant women at 24–28 weeks gestation at the First Affiliated Hospital of Harbin Medical University. Principal components analysis (PCA) and partial least squares-discriminatory analysis (PLS-DA) models were established to distinguish HP, GDM, and healthy, pregnant control individuals. Univariate and multivariate statistical analyses and Random Forest (RF) were used to identify and map co-metabolites to corresponding pathways in the disease states. Finally, risk factors for the disease were assessed by receiver operating characteristics (ROC) analysis. Dietary survey results showed that HP and GDM patients consumed a high-energy diet and the latter also consumed a high-carbohydrate and high-fat diet. Univariate analysis of clinical indices revealed HP and GDM patients had glycolipid disorders, with the former possessing more severe organ dysfunction. Subsequently, co-areas with significant differences identified by basic discriminant analyses and RF revealed lower levels of pyroglutamic acid and higher levels of 2-hydroxybutyric acid and glutamic acid in the GDM group. The number of metabolites increased in the HP group as compared to the healthy pregnant control group, including pyroglutamic acid, γ-aminobutyric acid (GABA), glutamic acid, oleic acid (C18:1), and palmitic acid (C16:0). ROC curves indicated that area under curve (AUC) for pyroglutamic acid in the GDM group was 0.962 (95% CI, 0.920–1.000), and the AUC of joint indicators, including pyroglutamic acid and GABA, in the HP group was 0.972 (95% CI, 0.938–1.000). Collectively, these results show that both GDM and HP patients at mid-gestation possessed dysregulated glucose and lipid metabolism, which may trigger oxidative stress via glutathione metabolism and biosynthesis of unsaturated fatty acids.

Pharmacological and Nutritional Modulation of Metabolome and Metagenome in Cardiometabolic Disorders

“…Other microbiota-derived metabolites, such as 2-hydroxy-3-methylbutyric acid and 2-hydroxybutyric acid, were negatively associated with dairy consumption and dairy-microbial scores. In recent studies, 2-hydroxybutyric acid has been shown to be associated with impaired glucose metabolism [ 91 , 92 ].…”

Plasma Metabolic Profiling and Multiclass Diagnostic Model Development for Stable Angina Pectoris and Acute Myocardial Infarction

“… 28 These two metabolites exhibit similar expression trends, which are consistent with the findings of this study. Similarly, 2-hydroxybutyric acid, which may arise from increased lipid oxidation and oxidative stress, exacerbates insulin resistance, shows an increasing trend in patients with diabetes, 29 and is considered a biomarker of impaired glucose tolerance. 30 Fish oil typically contains three types of n-3 long-chain polyunsaturated fatty acids: eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with n-3 DPA being a metabolic extension of EPA and an intermediate between EPA and DHA.…”

Genomic and metabonomic methods reveal the probiotic functions of swine-derived Ligilactobacillus salivarius

“…2-ethyl-2-hydroxybutyric acid is an anticonvulsant and hypnotic agent that can improve sleep [ 37 , 38 ]. N-lactoyl-phenylalanine, secreted after physical exercise, inhibits appetite in obese individuals [ 39 , 40 ].…”