Early pregnancy urinary biomarkers of fatty acid and carbohydrate metabolism in pregnancies complicated by gestational diabetes

Abstract

Aims Alterations in organic acid biomarkers from fatty acid and carbohydrate metabolism have been documented in type 2 diabetes patients. However, their association with gestational diabetes mellitus (GDM) is largely unknown. Methods Participants were 25 GDM cases and 25 non-GDM controls. Biomarkers of fatty acid (adipate, suberate and ethylmalonate) and carbohydrate (pyruvate, l-lactate and β-hydroxybutyrate) metabolism were measured in maternal urine samples collected in early pregnancy (17 weeks) using liquid chromatography–mass spectrometry methods. Logistic regression were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Results GDM cases and controls differed in median urinary concentrations of ethylmalonate (3.0 vs. 2.3 µg/mg creatinine), pyruvate (7.4 vs. 2.1 µg/mg creatinine), and adipate (4.6 vs. 7.3 µg/mg creatinine) (all p-values <0.05). Women in the highest tertile for ethylmalonate or pyruvate concentrations had 11.4-fold (95%CI 1.10–117.48) and 3.27-fold (95%CI 0.72–14.79) increased risk of GDM compared with women in the lowest tertile for ethylmalonate and pyruvate concentrations, respectively. Women in the highest tertile for adipate concentrations, compared with women in the lowest tertile, had an 86% reduction in GDM risk (95%CI 0.02–0.97). Conclusions These preliminary findings underscore the importance of altered fatty acid and carbohydrate metabolism in the pathogenesis of GDM.

Maternal Early Pregnancy Serum Metabolomics Profile and Abnormal Vaginal Bleeding as Predictors of Placental Abruption: A Prospective Study

“…Incomplete fatty acid oxidation results in elevated acylcarnitine concentrations [ 25 ], which is used in newborn screening to detect metabolic disorders. [ 26 ] Furthermore, alterations in concentrations of certain acylcarnitines have been documented in women with gestational diabetes mellitus [ 27 ] and in women with hypertensive disorders of pregnancy [ 28 ]. On balance, our observations are consistent with an emerging literature suggesting impaired mitochondrial function in the pathogenesis of abruption.…”

Early Pregnancy Maternal Blood DNA Methylation in Repeat Pregnancies and Change in Gestational Diabetes Mellitus Status—A Pilot Study

“…22 Mitochondrial function in tissues (including liver, muscle, adipose tissue, and pancreatic beta cells) is critical in cellular metabolism and maintenance of adaptive responses that balance oxidative activity and nutrient load. 23,24 The imbalance that follows failure of complete oxidation, due to suboptimal mitochondrial oxidative activity, leads to the accumulation of lipid intermediates, incomplete fatty acid oxidation products, and ROS, which may induce both insulin resistance and altered secretion. 23 Another novel gene, related to a hypermethylated site, is the SEPT11 gene encoding a protein that belongs to the conserved septin family of filamentforming cytoskeletal GTPases that are involved in a variety of cellular functions including cytokinesis and vesicle trafficking.…”

Assessing Urinary Metabolomics in Giant Pandas Using Chromatography/Mass Spectrometry: Pregnancy-Related Changes in the Metabolome

“…These studies can be performed using maternal blood, urine, amniotic fluid, and placental tissue. To date, urine has been used as a biological matrix for metabolomic analysis to study the relationship between gestational diabetes mellitus and metabolic disorders (19) to identify urinary biomarkers of aberrant fatty acid and carbohydrate metabolism in early pregnancies complicated by gestational diabetes (20), identify potential biomarkers of fetal malformation and premature delivery in the second trimester (21), and study urinary metabolic changes during and after pregnancy (22). Urinary metabolomics plays an important role in the study of gestational stages in human pregnancy, but to date, the metabolomics of pregnant giant pandas has not been analyzed.…”