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Effects of dynamic change in fetuin-A levels from the first to the second trimester on insulin resistance and gestational diabetes mellitus: a nested case-control study.

ABSTRACT: OBJECTIVE:To examine the effects of dynamic change in fetuin-A levels before the diagnosis of gestational diabetes mellitus (GDM) on insulin resistance and GDM. RESEARCH DESIGN AND METHODS:A total of 135 women with GDM and 135 normal glucose tolerance (NGT) women with matched age (±2 years old) and gestational age at taking the oral glucose tolerance test (OGTT) were included in this nested case-control study. Fasting venous blood samples were collected at the prenatal visit of the first trimester and during OGTT of the second trimester. Plasma concentration of fetuin-A and insulin was determined. RESULTS:The plasma fetuin-A concentration in women with GDM was significantly higher than NGT controls in both the first trimester (medians: 403.0?pg/mL vs 273.4?pg/mL; p<0.05) and the second trimester (medians: 475.7?pg/mL vs 290.8?pg/mL; p<0.05) and notably increased from the first to the second trimester. Multivariate linear regression analysis showed that the change in fetuin-A concentration was associated with the changes in fasting insulin, homeostasis model assessment (HOMA) of insulin resistance, and HOMA of ?-cell function (HOMA-?) (p<0.05). The highest quartile of the increase in fetuin-A concentration from the first to the second trimester was associated with a higher risk of developing GDM compared with the lowest quartile (OR 2.14; 95%?CI 1.05 to 4.37). CONCLUSIONS:The dynamic change in fetuin-A levels was associated with the changes in insulin resistance and ?-cell function from the first to the second trimester, and was associated with an increased risk of the development of GDM, indicating that fetuin-A could be a biomarker to predict the risk of GDM. TRIAL REGISTRATION NUMBER:NCT03814395.

SUBMITTER: Jin C

PROVIDER: S-EPMC7039607 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Effects of dynamic change in fetuin-A levels from the first to the second trimester on insulin resistance and gestational diabetes mellitus: a nested case-control study.

Jin Chuyao C Lin Lizi L Han Na N Zhao Zhiling Z Liu Zheng Z Luo Shusheng S Xu Xiangrong X Liu Jue J Wang Haijun H

BMJ open diabetes research & care 20200101 1

<h4>Objective</h4>To examine the effects of dynamic change in fetuin-A levels before the diagnosis of gestational diabetes mellitus (GDM) on insulin resistance and GDM.<h4>Research design and methods</h4>A total of 135 women with GDM and 135 normal glucose tolerance (NGT) women with matched age (±2 years old) and gestational age at taking the oral glucose tolerance test (OGTT) were included in this nested case-control study. Fasting venous blood samples were collected at the prenatal visit of th ...[more]

PMID: 31958310

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Project description:Maternal thyroid alterations have been widely associated with the risk of gestational diabetes mellitus (GDM). This study aims to 1) test the first and the second trimester full maternal thyroid profile on the prediction of GDM, both alone and combined with non-thyroid data; and 2) make that prediction independent of the diagnostic criteria, by evaluating the effectiveness of the different maternal variables on the prediction of oral glucose tolerance test (OGTT) post load glycemia. Pregnant women were recruited in Concepción, Chile. GDM diagnosis was performed at 24-28 weeks of pregnancy by an OGTT (n = 54 for normal glucose tolerance, n = 12 for GDM). 75 maternal thyroid and non-thyroid parameters were recorded in the first and the second trimester of pregnancy. Various combinations of variables were assessed for GDM and post load glycemia prediction through different classification and regression machine learning techniques. The best predictive models were simplified by variable selection. Every model was subjected to leave-one-out cross-validation. Our results indicate that thyroid markers are useful for the prediction of GDM and post load glycemia, especially at the second trimester of pregnancy. Thus, they could be used as an alternative screening tool for GDM, independently of the diagnostic criteria used. The final classification models predict GDM with cross-validation areas under the receiver operating characteristic curve of 0.867 (p<0.001) and 0.920 (p<0.001) in the first and the second trimester of pregnancy, respectively. The final regression models predict post load glycemia with cross-validation Spearman r correlation coefficients of 0.259 (p = 0.036) and 0.457 (p<0.001) in the first and the second trimester of pregnancy, respectively. This investigation constitutes the first attempt to test the performance of the whole maternal thyroid profile on GDM and OGTT post load glycemia prediction. Future external validation studies are needed to confirm these findings in larger cohorts and different populations.

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.

Dataset Information

Effects of dynamic change in fetuin-A levels from the first to the second trimester on insulin resistance and gestational diabetes mellitus: a nested case-control study.

Publications

Effects of dynamic change in fetuin-A levels from the first to the second trimester on insulin resistance and gestational diabetes mellitus: a nested case-control study.

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