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Metabolomics signatures associated with an oral glucose challenge in pregnant women.

ABSTRACT: AIM:The oral glucose tolerance test (OGTT), widely used as a gold standard for gestational diabetes mellitus (GDM) diagnosis, provides a broad view of glucose pathophysiology in response to a glucose challenge. We conducted the present study to evaluate metabolite changes before and after an oral glucose challenge in pregnancy; and to examine the extent to which metabolites may serve to predict GDM diagnosis in pregnant women. METHODS:Peruvian pregnant women (n=100) attending prenatal clinics (mean gestation 25 weeks) participated in the study with 23% of them having GDM diagnosis. Serum samples were collected immediately prior to and 2-hours after administration of a 75-g OGTT. Targeted metabolic profiling was performed using a LC-MS based metabolomics platform. Changes in metabolite levels were evaluated using paired Student's t-tests and the change patterns were examined at the level of pathways. Multivariate regression procedures were used to examine metabolite pairwise differences associated with subsequent GDM diagnosis. RESULTS:Of the 306 metabolites detected, the relative concentration of 127 metabolites were statistically significantly increased or decreased 2-hours after the oral glucose load (false discovery rate [FDR] corrected P-value<0.001). We identified relative decreases in metabolites in acylcarnitines, fatty acids, and diacylglycerols while relative increases were noted among bile acids. In addition, we found that C58:10 triacylglycerol (?=-0.08, SE=0.04), C58:9 triacylglycerol (?=-0.07, SE=0.03), adenosine (?=0.70, SE=0.32), methionine sulfoxide (?=0.36, SE=0.13) were significantly associated with GDM diagnosis even after adjusting for age and body mass index. CONCLUSIONS:We identified alterations in maternal serum metabolites, representing distinct cellular and metabolic pathways including fatty acid metabolism, in response to an oral glucose challenge. These findings offer novel perspectives on the pathophysiological mechanisms underlying GDM.

SUBMITTER: Gelaye B

PROVIDER: S-EPMC6041194 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Metabolomics signatures associated with an oral glucose challenge in pregnant women.

Gelaye B B Clish C B CB Denis M M Larrabure G G Tadesse M G MG Deik A A Pierce K K Bullock K K Dennis C C Enquobahrie D A DA Williams M A MA

Diabetes & metabolism 20180111 1

<h4>Aim</h4>The oral glucose tolerance test (OGTT), widely used as a gold standard for gestational diabetes mellitus (GDM) diagnosis, provides a broad view of glucose pathophysiology in response to a glucose challenge. We conducted the present study to evaluate metabolite changes before and after an oral glucose challenge in pregnancy; and to examine the extent to which metabolites may serve to predict GDM diagnosis in pregnant women.<h4>Methods</h4>Peruvian pregnant women (n=100) attending pren ...[more]

PMID: 29395809

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Project description:BackgroundPhthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes.ObjectiveTo explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort.MethodsWe measured 19 urinary phthalate metabolites during 24-28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalate metabolites and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, mono-unsaturated, polyunsaturated) which were then regressed on phthalate metabolites. Associations were adjusted for false discovery.ResultsAfter controlling for multiple comparisons, 33 phthalate-lipid associations were identified (False discovery rate adjusted p value < 0.05), and diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1 were the most strongly associated with multiple phthalate metabolites. Metabolites of di-2-ethylhexyl phthalate, bis(2-ethylhexyl) phthalate, dibutyl phthalates, and diisobutyl phthalate were associated with increased ceramides, lysophosphatidylcholines, lysophosphatidylethanolamines, and triacylglycerols, particularly those containing saturated and mono-unsaturated fatty acid chains.SignificanceCharacterization of associations between lipidomic markers and phthalate metabolites during pregnancy will yield mechanistic insight for maternal and child health outcomes.ImpactThis study leverages emerging technology to evaluate lipidome-wide signatures of phthalate exposure during pregnancy. The greatest lipid signatures of phthalate exposure were observed for diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1. Polymerized glycerides are important for energy production and regulated through hormone signaling, while plasmenyl-phosphatidylcholines have been implicated in membrane dynamics and important for cell-to-cell signaling. Characterization of these mechanisms are relevant for informing the etiology of maternal and children's health outcomes.

Project description:BackgroundThe oral health status of pregnant women in low-resource communities such as Nepal has not been well characterized. This sub-population is also of specific interest given associations between poor oral health and adverse pregnancy outcomes previously documented in other settings. We explored relationships between gingivitis and risk factors among pregnant women in rural Nepal.MethodsThe design was a community-based, cross-sectional study in a sub-area of Sarlahi District, Nepal. Pregnant women < 26 weeks gestation underwent clinical periodontal exams conducted by community-based oral health workers. Exams included a full mouth assessment measuring bleeding on probing (BOP), probing depth (PD) (six sites per tooth), and gingival recession, the distance from the cemento-enamel junction to the free gingival margin (two direct sites per tooth). Data on participant risk factors were collected through household surveys, including demographic characteristics, oral health behaviors, care seeking, and health attitudes. Multivariable logistic regression modeling was used to assess relationships between gingivitis and risk factors.ResultsWe enrolled 1452 participants, of which 40% (n = 582) had signs of clinical gingivitis and 60% (n = 870) clinical health. Average participant age was 23. Most participants (88%) had never received oral health care. Participants averaged 10% of sites with BOP with most (79%) having ≥1 site with BOP. Nine percent of participants had ≥1 site with PD ≥4 mm, although very few participants (0.7%) had sites with PD ≥5 mm. Few participants (13%) had any recession (≥1 mm). In the final adjusted model, odds of gingivitis increased by 3% for each year of age (aOR 1.03, 95% CI 1.00, 1.06) and were higher for women of short maternal stature (< 150 cm) (aOR 1.43, 95% CI: 1.14, 1.79) and among women reporting cost to be a barrier to seeking dental care (aOR 2.13, 95% CI: 1.09, 4.15).ConclusionsGingivitis was common and associated with age, maternal stature, self-reported high cost of dental care, and other risk factors among pregnant women in rural Nepal.Trial registrationClinicalTrials.gov Identifier: NCT01177111 (Nepal Oil Massage Study) and NCT02788786 (Pilot Trial).

Project description:Preeclampsia is a leading cause of maternal and fetal mortality worldwide, yet its exact pathogenesis remains elusive. This study, nested within the Vitamin D Antenatal Asthma Reduction Trial (VDAART), aimed to develop integrated omics models of preeclampsia that have utility in both prediction and in the elucidation of underlying biological mechanisms. Metabolomic profiling was performed on first trimester plasma samples of 47 pregnant women from VDAART who subsequently developed preeclampsia and 62 controls with healthy pregnancies, using liquid-chromatography tandem mass-spectrometry. Metabolomic profiles were generated based on logistic regression models and assessed using Received Operator Characteristic Curve analysis. These profiles were compared to profiles from generated using third trimester samples. The first trimester metabolite profile was then integrated with a pre-existing transcriptomic profile using network methods. In total, 72 (0.9%) metabolite features were associated (p<0.01) with preeclampsia after adjustment for maternal age, race, and gestational age. These features had moderate to good discriminatory ability; in ROC curve analyses a summary score based on these features displayed an area under the curve (AUC) of 0.794 (95%CI 0.700, 0.888). This profile retained the ability to distinguish preeclamptic from healthy pregnancies in the third trimester (AUC:0.762 (95% CI 0.663, 0.860)). Additionally, metabolite set enrichment analysis identified common pathways, including glycerophospholipid metabolism, at the two time-points. Integration with the transcriptomic signature refined these results suggesting a particular role for lipid imbalance, immune function and the circulatory system. These findings suggest it is possible to develop a predictive metabolomic profile of preeclampsia. This profile is characterized by changes in lipid and amino acid metabolism and dysregulation of immune response and can be refined through interaction with transcriptomic data. However validation in larger and more diverse populations is required.

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Metabolomics signatures associated with an oral glucose challenge in pregnant women.

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Metabolomics signatures associated with an oral glucose challenge in pregnant women.

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