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An Unbiased Lipidomics Approach Identifies Early Second Trimester Lipids Predictive of Maternal Glycemic Traits and Gestational Diabetes Mellitus.

ABSTRACT: OBJECTIVE:To investigate the relationship between early second trimester serum lipidomic variation and maternal glycemic traits at 28 weeks and to identify predictive lipid biomarkers for gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS:Prospective study of 817 pregnant women (discovery cohort, n = 200; validation cohort, n = 617) who provided an early second trimester serum sample and underwent an oral glucose tolerance test (OGTT) at 28 weeks. In the discovery cohort, lipids were measured using direct infusion mass spectrometry and correlated with OGTT results. Variable importance in projection (VIP) scores were used to identify candidate lipid biomarkers. Candidate biomarkers were measured in the validation cohort using liquid chromatography-mass spectrometry and tested for associations with OGTT results and GDM status. RESULTS:Early second trimester lipidomic variation was associated with 1-h postload glucose levels but not with fasting plasma glucose levels. Of the 13 lipid species identified by VIP scores, 10 had nominally significant associations with postload glucose levels. In the validation cohort, 5 of these 10 lipids had significant associations with postload glucose levels that were independent of maternal age and BMI, i.e., TG(51.1), TG(48:1), PC(32:1), PCae(40:3), and PCae(40:4). All except the last were also associated with maternal GDM status. Together, these four lipid biomarkers had moderate ability to predict GDM (area under curve [AUC] = 0.71 ± 0.04, P = 4.85 × 10-7) and improved the prediction of GDM by age and BMI alone from AUC 0.69 to AUC 0.74. CONCLUSIONS:Specific early second trimester lipid biomarkers can predict maternal GDM status independent of maternal age and BMI, potentially enhancing risk factor-based screening.

SUBMITTER: Lu L

PROVIDER: S-EPMC5123716 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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An Unbiased Lipidomics Approach Identifies Early Second Trimester Lipids Predictive of Maternal Glycemic Traits and Gestational Diabetes Mellitus.

Lu Liangjian L Koulman Albert A Petry Clive J CJ Jenkins Benjamin B Matthews Lee L Hughes Ieuan A IA Acerini Carlo L CL Ong Ken K KK Dunger David B DB

Diabetes care 20161004 12

<h4>Objective</h4>To investigate the relationship between early second trimester serum lipidomic variation and maternal glycemic traits at 28 weeks and to identify predictive lipid biomarkers for gestational diabetes mellitus (GDM).<h4>Research design and methods</h4>Prospective study of 817 pregnant women (discovery cohort, n = 200; validation cohort, n = 617) who provided an early second trimester serum sample and underwent an oral glucose tolerance test (OGTT) at 28 weeks. In the discovery co ...[more]

PMID: 27703025

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Project description:BackgroundGestational diabetes mellitus (GDM) is glucose intolerance first recognised during pregnancy. Both modalities and thresholds of the GDM diagnostic test, the Oral Glucose Tolerance Test (OGTT), have varied widely over time and among countries. Additionally, OGTT limitations include inconsistency, poor patient tolerability, and questionable diagnostic reliability. Many biological parameters have been reported to be modified by GDM and could potentially be used as diagnostic indicators. This study aimed to 1) systematically explore biomarkers reported in the literature as differentiating GDM from healthy pregnancies 2) screen those indicators assessed against OGTT to propose OGTT alternatives.Main bodyA systematic review of GDM diagnostic indicators was performed according to PRISMA guidelines (PROSPERO registration CRD42020145499). Inclusion criteria were full-text, comprehensible English-language articles published January 2009-January 2021, where a biomarker (from blood, ultrasound, amniotic fluid, placenta) was compared between GDM and normal glucose tolerance (NGT) women from the second trimester onward to immediately postpartum. GDM diagnostic method had to be clearly specified, and the number of patients per study higher than 30 in total or 15 per group. Results were synthesised by biomarkers.ResultsOf 13,133 studies identified in initial screening, 174 studies (135,801 participants) were included. One hundred and twenty-nine studies described blood analytes, one amniotic fluid analytes, 27 ultrasound features, 17 post-natal features. Among the biomarkers evaluated in exploratory studies, Adiponectin, AFABP, Betatrophin, CRP, Cystatin-C, Delta-Neutrophil Index, GGT, TNF-A were those demonstrating statistically and clinically significant differences in substantial cohorts of patients (> 500). Regarding biomarkers assessed versus OGTT (i.e. potential OGTT alternatives) most promising were Leptin > 48.5 ng/ml, Ficolin3/adiponectin ratio ≥ 1.06, Chemerin/FABP > 0.71, and Ultrasound Gestational Diabetes Score > 4. These all demonstrated sensitivity and specificity > 80% in adequate sample sizes (> / = 100).ConclusionsNumerous biomarkers may differentiate GDM from normoglycaemic pregnancy. Given the limitations of the OGTT and the lack of a gold standard for GDM diagnosis, advanced phase studies are needed to triangulate the most promising biomarkers. Further studies are also recommended to assess the sensitivity and specificity of promising biomarkers not yet assessed against OGTT.Trial registrationPROSPERO registration number CRD42020145499.

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An Unbiased Lipidomics Approach Identifies Early Second Trimester Lipids Predictive of Maternal Glycemic Traits and Gestational Diabetes Mellitus.

Publications

An Unbiased Lipidomics Approach Identifies Early Second Trimester Lipids Predictive of Maternal Glycemic Traits and Gestational Diabetes Mellitus.

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