scholarly journals First Trimester Metabolites Predict Gestational Diabetes Mellitus Diagnosis: A Case: Control Study (FS03-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Manuel Ramos ◽  
Anna Lamb ◽  
Noemi Alarcon ◽  
Adilene Quintana-Diaz ◽  
Rob Fanter ◽  
...  

Abstract Objectives Gestational Diabetes Mellitus (GDM) has an overall prevalence estimated as high as 13% of overweight/obese (OW/OB) pregnant women. Since the occurrence of GDM can have a combination of adverse perinatal outcomes and long-term increased risk of health issues in the future for both the mother and child, it is important that the mechanisms involved in this disease are better understood so that better prevention strategies can be devised. We sought to identify early and late pregnancy metabolites that discriminated women who developed vs. did not develop GDM to provide insight into its etiology and help improve treatments. Methods Participants were 26 OW/OB women enrolled in the Healthy Beginnings Trial and completed blood draws at 13 weeks, 26 weeks, and 35 weeks gestation. Participants from the control and dietary intervention group who developed GDM (N = 12) were matched on age and study entry BMI with those who did not develop GDM (N = 14). Plasma samples were analyzed by ultra-high-performance liquid chromatography-hybrid triple‐quadrupole linear ion trap mass spectrometry (UPLC-QTRAP) using two targeted metabolomics assays for primary metabolomics and aminomics. Results A total of 142 metabolites were identified. Most metabolite differences were observed during the first trimester blood draw, prior to GDM diagnosis. At first trimester, metabolites related to energy metabolism that were altered included lower levels of alpha-ketoglutarate and glycerol-3-phosphate, as well as the medium-chain acylcarnitines’ lauroyl-carnitine, dodecenoyl-carnitine, and octanoyl-carnitine (P < 0.05). Interestingly, the neurotransmitters serotonin and glutamate were elevated in subjects who later developed GDM (P < 0.01). In regards to the observed elevated creatine, the lower concentrations of methionine and glycine may suggest utilization of these amino acids for its production (P < 0.03). Lastly, the gut microbiota-derived indole-3-propionate was higher in GDM cases (P < 0.05). In the third trimester of the GDM group, only levels of 4-pyridoxate (vitamin B-6) were lowered (P < 0.05). Conclusions Metabolic changes associated with the numerous plasma metabolites that were different between GDM case-control subjects during first trimester may predict the development of this condition. Funding Sources NIH, ARI.

Author(s):  
Xinmei Huang ◽  
Bingbing Zha ◽  
Manna Zhang ◽  
Yue Li ◽  
Yueyue Wu ◽  
...  

Abstract Objective The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. Here, we investigated the potential effect of monocytes in GDM. Materials and Methods: Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages and their products were measured. Results Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and closely associated with glucose level, insulin resistance and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia in both the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 10 9/L. Notably, CD206 and IL-10 were significantly lower, while CD80, CD86, TNF-α and IL-6 were higher in both GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α and IL-6. Conclusions Decreased monocyte count throughout pregnancy was closely-associated with the development of GDM, macrosomia and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.


2019 ◽  
Vol 47 (2) ◽  
pp. 161-168 ◽  
Author(s):  
Paula J. Correa ◽  
Pia Venegas ◽  
Yasna Palmeiro ◽  
Daniela Albers ◽  
Gregory Rice ◽  
...  

AbstractObjectivesTo evaluate the first trimester maternal biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM).MethodsThe study was a case-control study of healthy women with singleton pregnancies at the first trimester carried out at the Obstetrics and Gynecology Unit, Clinica Davila, Santiago, Chile. After obtaining informed consent, peripheral blood samples of pregnant women under 14 weeks of gestation were collected. At 24–28 weeks of pregnancy, women were classified as GDM (n=16) or controls (n=80) based on the results of a 75-g oral glucose tolerance test (OGTT). In all women, we measured concentrations of fasting blood glucose, insulin, glycated hemoglobin, uric acid, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), sex hormone-binding globulin (SHBG), adiponectin, tissue plasminogen activator (t-PA), leptin and placental growth factor (PGF).ResultsThe GDM group displayed an increased median concentration of cholesterol (P=0.04), triglycerides (P=0.003), insulin (P=0.003), t-PA (P=0.0088) and homeostatic model assessment (HOMA) (P=0.003) and an increased mean concentration of LDL (P=0.009) when compared to the control group. The receiver operating characteristic (ROC) curve for significant variables achieved an area under the curve (AUC) of 0.870, a sensitivity of 81.4% and a specificity of 80.0%. The OGTT was positive for GDM according to the IADPSG (International Diabetes in Pregnancy Study Group) criteria.ConclusionWomen who subsequently developed GDM showed higher levels of blood-borne biomarkers during the first trimester, compared to women who did not develop GDM. These data warrant validation in a larger cohort.


BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e025908 ◽  
Author(s):  
Maëlle Dandjinou ◽  
Odile Sheehy ◽  
Anick Bérard

ObjectivesThe aim of this study was to determine the association between antidepressant (AD) classes, types and duration of use during pregnancy and the risk of gestational diabetes mellitus (GDM).Design and settingA nested case–control study was conducted within the Quebec Pregnancy Cohort (QPC), a Canadian provincial database which includes data on all pregnancies and children in Quebec from January 1998 to December 2015.Primary outcome measuresGestational diabetes mellitus.ParticipantsCases of GDM were identified after week 20 of pregnancy and randomly matched 1:10 to controls on gestational age at index date (ie, calendar date of GDM) and year of pregnancy. AD exposure was assessed by filled prescriptions between the beginning of pregnancy (first day of last menstrual period) and index date. Conditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR).ResultsAmong 20 905 cases and 209 050 matched controls, 9741 (4.2%) women were exposed to ADs. When adjusting for potential confounders, AD use was associated with an increased risk of GDM (aOR 1.19, 95% CI 1.08 to 1.30); venlafaxine (aOR 1.27, 95% CI 1.09 to 1.49) and amitriptyline (aOR 1.52, 95% CI 1.25 to 1.84) were also associated with an increased risk of GDM. Moreover, the risk of GDM was increased with longer duration of AD use, specifically for serotonin norepinephrine reuptake inhibitors, tricyclic ADs and combined use of two AD classes. No statistically significant association was observed for selective serotonin reuptake inhibitors.ConclusionThe findings suggest that ADs—and specifically venlafaxine and amitriptyline—were associated with an increased risk of GDM.


Author(s):  
Yan-Ting Wu ◽  
Chen-Jie Zhang ◽  
Ben Willem Mol ◽  
Andrew Kawai ◽  
Cheng Li ◽  
...  

Abstract Context Accurate methods for early gestational diabetes mellitus (GDM) (during the first trimester of pregnancy) prediction in Chinese and other populations are lacking. Objectives Establishing effective models to predict early GDM. Setting Pregnancy data for 73 variables during the first trimester were extracted from the electronic medical record system. Main measures Based on a machine learning (ML) driven feature selection method, 17 variables were selected for early GDM prediction. In order to facilitate clinical application, 7 variables were selected from the 17-variable panel. Advanced ML approaches were then employed using the 7-variable dataset and the 73-variable dataset to build models predicting early GDM for different situations respectively. Results 16,819 and 14,992 cases were included in the training and testing sets, respectively. Using 73 variables, the deep neural network model achieved high discriminative power, with area under the curve (AUC) values of 0.80. The 7-variable logistic regression (LR) model also achieved effective discriminate power (AUC = 0.77). Low BMI (≤ 17) was related to an increased risk of GDM, compared to a BMI in the range of 17 to 18 (minimum risk interval) (11.8% vs 8.7%, P = 0.0935). TT3 and TT4 were superior to FT3 and FT4 in predicting GDM. Lipoprotein (a) was demonstrated a promising predictive value (AUC = 0.66). Conclusions We employed ML models that achieved high accuracy in predicting GDM in early pregnancy. A clinically cost-effective 7-variable LR model was simultaneously developed. The relationship of GDM with thyroxine and BMI was investigated in the Chinese population.


2021 ◽  
Author(s):  
Peng Tang ◽  
Jun Liang ◽  
Qian Liao ◽  
Huishen Huang ◽  
Xiaojing Guo ◽  
...  

Abstract A growing number of epidemiologic studies have estimated the associations between endocrine-disrupting chemicals and gestational diabetes mellitus (GDM). However, reports on the association between bisphenol A (BPA) substitutes and GDM are limited. This investigation aimed to explore the associations of maternal serum BPA, bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) with the risk of GDM. A nested case-control study was performed among 500 pregnant women. Associations between the serum bisphenol levels and the risk of GDM were assessed by conditional logistic regression analysis and two-mixture modeling approaches (Bayesian kernel machine regression [BKMR] and quantile g-computation). BPA and TBBPA were negatively associated with the risk of GDM in the adjusted models, respectively. Intermediate BPS levels were associated with increased odds (OR: 1.84; 95% CI: 1.04, 3.27) of GDM compared with the low concentration groups only based on the single-bisphenol models. Associations between BPA, BPS, and TBBPA with the risk of GDM were also found in the BKMR analysis. The quantile g-computation (OR: 0.55; 95% CI: 0.43, 0.69) and BKMR models revealed a statistically significant and negative joint effect of the five bisphenols on the risk of GDM. This study demonstrates the association between exposure to BPS with the increased risk of GDM. In addition, exposure to BPA and TBBPA were associated with the reduced risk of GDM. Moreover, exposure to the mixture of the five bisphenols was negatively associated with the risk of GDM.


PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262618
Author(s):  
Louise Søndergaard Rold ◽  
Caspar Bundgaard-Nielsen ◽  
Julie Niemann Holm-Jacobsen ◽  
Per Glud Ovesen ◽  
Peter Leutscher ◽  
...  

Background The incidence of women developing gestational diabetes mellitus (GDM) is increasing, which is associated with an increased risk of type 2 diabetes mellitus (T2DM) for both mother and child. Gut microbiota dysbiosis may contribute to the pathogenesis of both GDM and the accompanying risk of T2DM. Thus, a better understanding of the microbial communities associated with GDM could offer a potential target for intervention and treatment in the future. Therefore, we performed a systematic review to investigate if the GDM women have a distinct gut microbiota composition compared to non-GDM women. Methods We identified 21 studies in a systematic literature search of Embase and PubMed up to February 24, 2021. Data on demographics, methodology and identified microbial metrics were extracted. The quality of each study was assessed according to the Newcastle-Ottawa Scale. Results Sixteen of the studies did find a GDM-associated gut microbiota, although no consistency could be seen. Only Collinsella and Blautia showed a tendency to be increased in GDM women, whereas the remaining genera were significantly different in opposing directions. Conclusion Although most of the studies found an association between GDM and gut microbiota dysbiosis, no overall GDM-specific gut microbiota could be identified. All studies in the second trimester found a difference between GDM and non-GDM women, indicating that dysbiosis is present at the time of diagnosis. Nevertheless, it is still unclear when the dysbiosis develops, as no consensus could be seen between the studies investigating the gut microbiota in the first trimester of pregnancy. However, studies varied widely concerning methodology and study design, which might explain the highly heterogeneous gut microbiota compositions between studies. Therefore, future studies need to include multiple time points and consider possible confounding factors such as ethnicity, pre-pregnancy body mass index, and GDM treatment.


Author(s):  
P. V. Popova ◽  
A. S. Gerasimov ◽  
E. N. Kravchuk ◽  
E. S. Shelepova ◽  
E. M. Ryazantseva ◽  
...  

Objective. To determine the relationship between blood pressure measured during the first trimester of pregnancy and the risk of the development of gestational diabetes mellitus. Design and methods. A total of 209 pregnant women were screened for gestational diabetes mellitus between weeks 24 and 28 of gestation, as defined by WHO criteria. Blood pressure, weight and waist circumference data were obtained by review of the medical records. Results. An elevated blood pressure at first trimester of pregnancy was associated with a six-fold increase in the risk of the development of gestational diabetes mellitus (OR = 5.8, 95 % CI 1.9-17.5, p = 0.001) compared with non-hypertensive women. Arterial hypertension (including controlled forms) in the first trimester of pregnancy was followed by a three-fold (OR = 3.04, 95 % CI 1.5-6.3) increase in the risk of gestational diabetes mellitus compared with non-hypertensive women (p = 0.005). Conclusion. Obtained data indicate that women with elevated blood pressure in the first trimester of pregnancy have an increased risk of the development of gestational diabetes mellitus.


Author(s):  
Kristin S. Magnusdottir ◽  
Ellen A. Tryggvadottir ◽  
Ola K. Magnusdottir ◽  
Laufey Hrolfsdottir ◽  
Thorhallur I. Halldorsson ◽  
...  

Background: Vitamin D deficiency has been associated with an increased risk of gestational diabetes mellitus (GDM), one of the most common pregnancy complications. The vitamin D status has never previously been studied in pregnant women in Iceland. Objective: The aim of this research study was to evaluate the vitamin D status of an Icelandic cohort of pregnant women and the association between the vitamin D status and the GDM incidence. Design: Subjects included pregnant women (n = 938) who attended their first ultrasound appointment, during gestational weeks 11–14, between October 2017 and March 2018. The use of supplements containing vitamin D over the previous 3 months, height, pre-pregnancy weight, and social status were assessed using a questionnaire, and blood samples were drawn for analyzing the serum 25‑hydroxyvitamin D (25OHD) concentration. Information regarding the incidence of GDM later in pregnancy was collected from medical records. Results: The mean ± standard deviation of the serum 25OHD (S-25OHD) concentration in this cohort was 63±24 nmol/L. The proportion of women with an S-25OHD concentration of ≥ 50 nmol/L (which is considered adequate) was 70%, whereas 25% had concentrations between 30 and 49.9 nmol/L (insufficient) and 5% had concentrations < 30 nmol/L (deficient). The majority of women (n = 766, 82%) used supplements containing vitamin D on a daily basis. A gradual decrease in the proportion of women diagnosed with GDM was reported with increasing S-25OHD concentrations, going from 17.8% in the group with S-25OHD concentrations < 30 nmol/L to 12.8% in the group with S-25OHD concentrations ≥75 nmol/L; however, the association was not significant (P for trend = 0.11). Conclusion: Approximately one-third of this cohort had S-25OHD concentrations below adequate levels (< 50 nmol/L) during the first trimester of pregnancy, which may suggest that necessary action must be taken to increase their vitamin D levels. No clear association was observed between the vitamin D status and GDM in this study.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangrong Xu ◽  
Yuanyuan Wang ◽  
Na Han ◽  
Xiangming Yang ◽  
Yuelong Ji ◽  
...  

ObjectiveThe extensive use of rare earth elements (REEs) in many technologies was found to have effects on human health, but the association between early pregnancy exposure to REEs and gestational diabetes mellitus (GDM) is still unknown.MethodsThis nested case-control study involved 200 pregnant women with GDM and 200 healthy pregnant women from the Peking University Birth Cohort in Tongzhou. We examined the serum concentrations of 14 REEs during early pregnancy and analyzed their associations with the risk of GDM.ResultsWhen the elements were considered individually in the logistic regression model, no significant associations were found between REEs and GDM, after adjusting for confounding variables (P &gt; 0.05). In weighted quantile sum (WQS) regression, each quartile decrease in the mixture index for REEs resulted in a 1.67-fold (95% CI: 1.12-2.49) increased risk of GDM. Neodymium (Nd), Praseodymium (Pr), and Lanthanum (La) were the most important contributors in the mixture.ConclusionThe study findings indicated that early pregnancy exposure to lower levels of REE mixture was associated with an increased risk of GDM, and Nd, Pr, and La exhibited the strongest effects in the mixture.


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