Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Gestational diabetes mellitus (GDM) is characterized by glycemia and insulin disorders. Bile acids (BAs) have emerged as vital signaling molecules in glucose metabolic regulation. BA change in GDM is still unclear, which exerts great significance to illustrate the change of BAs in GDM. GDM patients and normal pregnant women were enrolled during the oral glucose tolerance test (OGTT) screening period. Fasting serums were sampled for the measurement of BAs. BA metabolism profiles were analyzed in both pregnant women with GDM and those with normal glucose tolerance (NGT). Delivery characteristics, delivery gestational age, and infant birthweight were extracted from medical records. GDM patients presented distinctive features compared with NGT patients, including higher body mass index (BMI), elevated serum glucose concentration, raised insulin (both fasting and OGTT), and increased hemoglobin A1c (HbA1c) levels. Higher homeostasis model assessment of insulin resistance (HOMA-IR) and decreased β-cell compensation (i.e., oral disposition index (DI

Retrospective analysis of OGTT results of 26 558 pregnant women / 公共卫生与预防医学

Objective To investigate the prevalence of gestational diabetes mellitus (GDM) among pregnant women in Wuhan, and to explore the application value of oral glucose tolerance test (OGTT) results in the screening, diagnosis and treatment of GDM. Methods A retrospective analysis was carried out on the OGTT results of 26 558 pregnant women from Hubei Maternal and Child Health Hospital from January 2018 to December 2018. Results (1) A total of 1 754 cases were diagnosed with GDM, with a positive rate of 6.60%. Among them of 776 had fasting blood glucose ≥5.1mmol/L, 880 had 1-hour blood glucose ≥10.0mmol/L, and 798 had 2-hour blood glucose ≥8.5mmol/L. (2) The positive rates of fasting blood glucose, 1-hour blood glucose, and 2-hour blood glucose in the ≥35-year-old age group were all over two times higher than those in the <35-year-old age group (all P<0.01). (3) The ratio of people with single-point positive, two-point positive and three-point positive was 7:2:1. (4) FBG, 1-hour blood glucose and 2-hour blood glucose concentrations were all positively correlated with each other (all P＜0.01). Among these, the positive correlation between 1-hour blood glucose and 2-hour blood glucose was the most significant (r=0.618, P＜0.01). Conclusions The incidence rate of GDM among pregnant women in Wuhan reached 6.60%, and the prevalence in pregnant women over 35 years old was significantly higher. Blood glucose level during pregnancy should be monitored for early detection and intervention to prevent the development of GDM. The relationship between blood glucose concentrations at different time points in the OGTT test had reference value for clinical diagnosis and treatment.

Association of Maternal Serum Ferritin Level in Gestational Diabetes Mellitus and its Effect on Cord Blood Hemoglobin

Introduction: Gestational Diabetes Mellitus is thedevelopment of carbohydrate intolerance of variable severitywith onset or first recognition during pregnancy. Many studieshad suggested that an elevated serum ferritin level in maternalblood in early as well as mid-pregnancy is an independent riskfactor for development of GDM. In the present study we aimto find the association of serum ferritin levels with serum ironand Hb% in the GDM patients at the time of delivery and alsocorrelate it with cord blood Hb% and iron levels of the newborn.Material and Methods: The study group was composed of50 diagnosed cases of GDM and the control group comprisedof age matched 50 cases of normal pregnancy. Maternal bloodwas used to measure mother’s hemoglobin, iron levels, serumferritin and hsCRP. Cord blood sample was used to estimatehemoglobin and iron levels of the newborns.Results: Our study shows that in the GDM cases the levelof serum ferritin was significantly higher (p <0.001) than inthe non GDM controls at the time of delivery. Cord bloodhemoglobin is negatively correlated with maternal serumferritin levels in GDM.Conclusion: Elevated serum ferritin level in GDM is a markerof inflammation due to increased ROS production caused byiron overload. This oxidative stress might affect the placentaliron transfer to the fetus and fetal Hb synthesis.

Role of sex hormone binding globulin as the early predictor for gestational diabetes mellitus

Background:  The aim of this study was to find role of SHBG as an early predictor for gestational diabetes mellitus.Methods: A hospital based prospective/observational/diagnostic and explorative study. The necessary information was collected from the participants through the prepared set of questionnaires. Pregnant women between 11 to 14 weeks of gestation who visited JSS OPD for antenatal checkup satisfying inclusion and exclusion criteria giving informed and written consent for the study were examined clinically. 3ml of venous blood was drawn with aseptic precautions for the estimation of SHBG and adiponectin. OGTT with 75gms glucose first done at 11 to 14weeks and again at 24-28 weeks and 32-36 weeks were done to the same patient to find out whether the patient developed GDM or not. These mothers were followed periodically till delivery. The sensitivity and specificity of SHBG were assessed and compared in patients who developed GDM.Results: 100 cases were selected for the study. About 12 patients were diagnosed as gestational diabetes mellitus in present study by OGCT at 32 weeks to 36 weeks. In present study about 14 patients had low level of SHBG. Low level of SHBG is found to be statistically significant in predicting GDM in first trimester.Conclusions: The combination of SHBG can be used as predictor of GDM in first trimester.

A Review on the Factors Influencing the Attendance of Postpartum Diabetes Screening for Mothers with Gestational Diabetes Mellitus

Abstract@#Women with gestational diabetes mellitus (GDM) during their pregnancy have a greater risk of developing overt diabetes mellitus and dysglycemia (prediabetes, impaired glucose tolerance or impaired fasting glucose) later in future, compared to mothers with normal pregnancy. Postpartum screening is crucial for early identification of type 2 diabetes (T2DM) in women with GDM. Nevertheless, despite various strategies, its rate remains low. A systematic review using databases of PubMed/Medline, Science Direct and CINAHL from 2008 to 2018, was conducted to identify the factors influencing the attendance of postpartum diabetes screening. Open access English articles, focusing on observational studies were reviewed. Primary screening of titles and abstracts of 91 articles were done, secondary screening of 31 articles resulted in 6 articles, included in this manuscript. Various factors identified to be associated with the attendance to postpartum diabetes screening, which are age, education, ethnicity, some obstetric factors like multiparty, and history of insulin usage previously. Many women fail to be screened for diabetes during the postpartum period, and this delays T2DM diagnosis, which in turn gives rise to various complications. Further research that considers these factors is necessary for developing interventions to improve postpartum T2DM screening for mothers with GDM during their pregnancy

Differences of intestinal flora between gestational diabetes mellitus pregnant women and healthy pregnant women / 上海交通大学学报（医学版）

Objective • To investigate the differences of intestinal flora between gestational diabetes mellitus (GDM) pregnant women and healthy pregnant women. Methods • In this study, 74 pregnant women from the Department of Obstetrics in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from Aug. 2017 to Jan. 2019 were recruited, including 51 GDM pregnant women (GDM group) and 23 healthy pregnant women (healthy group). High-throughput sequencing was performed on bacterial gene sequences from the fresh feces of all pregnant women by using Illumina MiSeq platform. Linear discriminant analysis (LDA) and LDA EffectSize (LEfSe) were used to detect the α diversity and expression abundance of intestinal flora of the two groups. Results • Compared with the healthy group, the intestinal flora richness of pregnant women in the GDM group was significantly higher (P=0.027). Porphyromonadaceae and Alcaligenaceae in Family, and Bacteroides in Genus of microbiota in the GDM group were significantly higher (all P<0.05). Compared with the GDM group, Burkholderiales, Lactobacillales and Bacillales in Order, Lachnospirace in Family, and Neisseria, Streptococcus, Butyricicoccusm, Gardnerella and Atopobium in Genus of microbiota in the healthy group were significantly higher (all P<0.05). Conclusion • There are significant differences of intestinal flora between GDM pregnant women and healthy pregnant women.

Dietary Characteristics of Women With Gestational Diabetes Mellitus

@#Introduction: The role of dietary intake on maternal glucose is uncertain. This study described the dietary characteristics of women with gestational diabetes mellitus (GDM) and examined the differences in dietary characteristics based on GDM diagnosis. Methods: This study recruited GDM women (n =45; age =31.1±5.1 years old) from health clinics in Seremban. Dietary intake, glycemic index (GI) and glycemic load (GL) were assessed using a semi-quantitative food frequency questionnaire (SFFQ) during first and second trimester of pregnancy. GDM diagnosis was made at 28 weeks gestation with the following cut-off for FPG ≥ 5.1 or 2hPG ≥ 7.8 mmol/L following oral glucose tolerance test. Results: Women with GDM had a reasonable intake of protein and fat but consumed high-carbohydrate at second trimester and high-sugar diet at both trimesters. Fibre, iron and calcium from the food sources did not meet the recommended nutrient intakes for pregnancy. About 75.6% (n = 34) GDM women had high 2hPG (9.3 ± 1.5 mmol/L) with a normal FPG (4.7 ± 0.7 mmol/L). While dietary characteristics were not significantly different, women with a higher 2hPG tended to take a higher proportion of protein at first trimester and a higher dietary GI, serving of rice, and sugars and creamer at second trimester than high FPG. Conclusion: Suboptimal maternal nutrition in women with GDM are of particular concern. Dietary characteristics of women with high fasting and 2-hour glucose were comparable but not optimal. The needs of tailored nutritional intervention are evident in women known to be at high risk of GDM.

Influence of high glucose on PRKAA1 expression and proliferation of trophoblast cells / 上海交通大学学报（医学版）

Objective: To explore the expression level of protein kinase AMP-activated catalytic subunit α1 (PRKAA1) in placental tissues of gestational diabetes mellitus (GDM) women, and the influence of high glucose (HG) on PRKAA1 expression and proliferation viability of trophoblast cells in vitro. Methods: The placental samples of GDM women (n=19) and normal pregnant women (n=20) of the corresponding period were collected. Real-time qPCR and Western blotting assay were used to detect the mRNA and protein levels of PRKAA1 in these biopsies, respectively. Trophoblast cells were treated by HG in vitro and then expression level of PRKAA1 was tested. CCK8 assay was used to detect proliferation viability of the cells treated by HG medium or inhibitor of PRKAA1, dorsomorphin. Results: Comparing to normal pregnant women, both mRNA and protein levels of PRKAA1 in placental tissues of GDM women significantly decreased (both P<0.05). HG treatment drastically downregulated expression of PRKAA1 in trophoblast cells in vitro (P<0.05). Both HG medium and dorsomorphin suppressed proliferation viability of trophoblast cells (both P<0.05). Conclusion: Expression level of PRKAA1 is dampened in placental tissues of GDM women. HG suppresses proliferation viability of trophoblast cells probably via downregulating PRKAA1 level in vitro.

Influence of high glucose on PRKAA1 expression and proliferation of trophoblast cells / 上海交通大学学报（医学版）

Objective·To explore the expression level of protein kinase AMP-activated catalytic subunit α1 (PRKAA1) in placental tissues of gestational diabetes mellitus(GDM)women,and the influence of high glucose(HG)on PRKAA1 expression and proliferation viability of trophoblast cells in vitro. Methods·The placental samples of GDM women (n=19) and normal pregnant women (n=20) of the corresponding period were collected. Real-time qPCR and Western blotting assay were used to detect the mRNA and protein levels of PRKAA1 in these biopsies, respectively. Trophoblast cells were treated by HG in vitro and then expression level of PRKAA1 was tested.CCK8 assay was used to detect proliferation viability of the cells treated by HG medium or inhibitor of PRKAA1, dorsomorphin. Results·Comparing to normal pregnant women, both mRNA and protein levels of PRKAA1 in placental tissues of GDM women significantly decreased (both P<0.05). HG treatment drastically downregulated expression of PRKAA1 in trophoblast cells in vitro(P<0.05).Both HG medium and dorsomorphin suppressed proliferation viability of trophoblast cells(both P<0.05). Conclusion·Expression level of PRKAA1 is dampened in placental tissues of GDM women.HG suppresses proliferation viability of trophoblast cells probably via downregulating PRKAA1 level in vitro.

Research progress on the correlation between gut microbiota and obstetrics and gynecology diseases / 上海交通大学学报（医学版）

The human gastrointestinal tract is colonized by 100 trillion microbes which is called the gut microbiome, whose number vastly outnumbers our bodies'. The gut microbiota plays an important role in the process of human health involved with evolution, development, metabolism and immune defense. However, it also has been found to be related with many human diseases. In recent years, an increasing number of studies have begun to reveal how these inhabitants played a role for obstetrics and gynecology related diseases. As discussed in this review, some imbalance of the microbiota ecosystem occurs in several diseases, such as polycystic ovarian syndrome, endometriosis, gestational diabetes mellitus and premature birth. Moreover, the reestablishment of the intestinal homeostasis has shown great effects on women related diseases as well as neonatal/childhood outcomes. This paper reviewed the correlation between gut microbiota and obstetrics and gynecology related diseases.

A Cross-sectional Study on Gestational Diabetes Mellitus and its Associated Risk Factors in Pregnant Women in a Tertiary Care Teaching Hospital in Udaipur

Background: Gestational Diabetes Mellitus (GDM) is the most common complication of pregnancy that may results into chronic hypertension, increased rate of cesarean delivery, fetal mortality and morbidity. Therefore, early diagnosis of GDM is very essential to reduce maternal and fetal morbidity. Moreover, it can reduce the onset of type 2 diabetes. Objectives: The main objective of this study was to determine the prevalence of GDM in pregnant women. Methods: A cross-sectional study was carried out at Department of Obstetrics and Gynaecology, Pacific Medical College & Hospital, Bhilo ka bedla, Udaipur  using a sample size of 46 pregnant women. Blood glucose levels were measured using glucose oxidase method with a glucometer. Data were analyzed by using Microsoft Office Excel and SPSS version 20. Results: Out of 46 pregnant women who participated in the study, 10.8% were found to have GDM with the mean ± 2SD of 198.12 ± 35.53 mg/dl of their blood glucose results. The highest proportion of GDM was revealed in pregnant women aged between 21 - 35 years. The lowest proportion of GDM fell in age group of 36 - 45 years. Conclusions: The findings of this study revealed that the prevalence of GDM was 10.8% and the most affected pregnant women were in the age group of 31 - 40 years.

Needs for Development of IT-based Nutritional Management Program for Women with Gestational Diabetes Mellitus / 대한지역사회영양학회지

OBJECTIVES: The aim of this study was to examine self-management status, nutritional knowledge, barrier factors in dietary management and needs of nutritional management program for women with Gestational Diabetes Mellitus (GDM). METHODS: A total of 100 women with GDM were recruited from secondary and tertiary hospitals in Seoul. The questionnaire composed of general characteristics, status of self-management, dietary habits, nutrition knowledge, barrier factors in dietary management, needs for nutrition information contents and nutritional management programs. Data were collected by a self-administered questionnaire. All data were statistically analyzed using student's t-test and chi-square test using SAS 9.3. RESULTS: About 35% of the subjects reported that they practiced medical nutrition and exercise therapy for GDM control. The main sources of nutrition information were ‘internet (50.0%)’ and ‘expert advice (45.0%)’. More than 70% of the subjects experienced nutrition education. The mean score of nutrition knowledge was 7.5 point out of 10, and only about half of the subjects were reported to be correctly aware of some questions such as ‘the cause of ketosis’, ‘the goal of nutrition management for GDM’, ‘the importance of sugar restriction on breakfast’. The major obstructive factors in dietary management were ‘eating more than planned when dining out’, ‘finding the appropriate menu when dining out’. The preferred nutrition information contents in developing management program were ‘nutritional information of food’, ‘recommended food by major nutrients’, ‘the relationship between blood glucose and food’, ‘tips on menu selection at eating out’. The subjects reported that they need management program such as ‘example of menu by calorie prescription’, ‘recommended weight gain guide’, ‘meal recording and dietary assessment’, ‘expert recommendation’, ‘sharing know-how’. CONCLUSIONS: Based on the results of this study, it is necessary to develop a program that provide personalized information by identifying the individual characteristics of the subjects and expert feedback function through various information and nutrition information contents that can be used in real life.

The use of insulin detemir in pregnancy with diabetes mellitus / 中国糖尿病杂志

[Summary] Poorly controlled hyperglycemia is closely associated with adverse outcomes during pregnancy. As the prevalence of diabetes rapidly increases ,the management of diabetes during pregnancy has been a significant and urgent need in clinical practice. This article reviewed the hot spots in the research field of gestational diabetes mellitus (GDM ) and pregnancy with diabetes mellitus ,including progresses on the risk factors for GDM and the long term effects of diabetes during pregnancy on mothers and offspring. This was followed by a body of evidences on the clinical benefits of improved glycemic control during pregnancy ,current therapeutic strategy using insulin as the golden standard as well as the potential advantage of insulin determir due to its unique pharmacokinetic‐pharmacodynamic (PK‐PD ) profile in this therapeutic area. Finally ,the authors summarized data from clinical trials on the usage of insulin detemir in pregnancy and in particular went over the designs and results of two randomly controlled trials investigating the efficacy and safety of insulin detemir in pregnancy patients with T1DM. Currently available data proved that insulin detemir was effective in improving glycemic control with a good safety profile in diabetic pregnant patients ,which may serve as an ideal choice in the management of diabetes during pregnancy.

Atención hospitalaria en la vigilancia obstétrica y metabólica de la gestante diabética, una experiencia de trabajo / Hospital attention in obstetric and metabolic surveillance in diabetic pregnant women; a work experience

Introducción: se conoce que en los últimos años, el manejo obstétrico ha enfatizado el control estricto de la glicemia en la madre y que ha mejorado la sobrevida fetal, la cual es directamente proporcional a la glicemia media materna. Objetivo: caracterizar los principales resultados en la experiencia hospitalaria sobre la vigilancia obstétrica y metabólica en la atención de gestantes diabéticas en el Hospital General Ciro Redondo García, Centro de Referencia Territorial en Artemisa. Métodos: se realizó un estudio observacional analítico, prospectivo y de corte longitudinal en el Hospital General Docente Ciro Redondo García de Artemisa desde junio de 2005 hasta junio de 2012. De un universo de 2 140 gestantes ingresadas, 240 fueron diagnosticadas diabéticas, constituyendo la muestra de estudio, Resultados: como diabéticas gestacionales (DG) se clasificó el 77,5 por ciento mientras que las diabéticas pregestacionales (DPG) constituyeron el 22,5 por ciento .Los grupos de edades de 31 a 36 años y de 20 a 25 años fueron los de mayor predominio en la diabetes gestacional pregestacional para un 29,1 por ciento y un 33,3 por ciento respectivamente. Los factores de riesgo de mayor predominio en el estudio fueron: la obesidad (44,2 por ciento ), la edad mayor de 34 años, polihidramnios, macrosomía previa y los abortos espontáneos (38,7; 18; 8,1; y 6,6 por ciento respectivamente). Otros factores de riesgo fueron los antecedentes familiares de diabetes mellitus de las gestantes, el diagnóstico de la diabetes gestacional después de las 20 semanas, la cesárea como el tipo de parto de mayor predominio y la edad gestacional a término al parto. Conclusiones: en un valorado sistema de salud pública como el cubano, se debe tomar medidas pertinentes para monitorear y controlar la morbilidad y complicaciones de las gestantes diabéticas

Background: it is known that, in recent years, obstetric management has made emphasis on the strict control of glycemia in the mother and the fetal survival has been improved, which is directly proportional to the mean maternal glycemia. Objective: to characterize the principal results in the hospital experience on obstetric and metabolic surveillance in the management of pregnant diabetic women in Ciro Redondo García General Hospital, Regional Reference Center in Artemisa. Methods: an observational analytical prospective cross-longitudinal study was conducted in Ciro Redondo García General Hospital in Artemisa from June 2005 to June 2012. From a universe of 2 140 pregnant women admitted in the hospital, 240 were diagnosed diabetics, representing them, the sample of the study. Results: the 77.5 percent of them were classified as gestational diabetic women (GD) whereas pregestational diabetic women (PGD) represented the 22.5 percent .The 31-36 and 20-25 age groups were the most predominant in gestational and pregestational diabetes, for a 29.1 percent and a 33.3 percent, respectively. The most predominant risk factors in the study were: obesity (44.2 percent ), age over 34 years, polyhydramnios, previous macrosomia, and spontaneous abortion (38.7, 18, 8.1, 6.6 percent respectively). Other risk factors were: family antecedents of diabetes mellitus in pregnant women, the time of diagnosis of gestational diabetes after the 20 weeks, the caesarean section as the most predominant type of delivery, and gestational age at delivery at term. Conclusions: in a valued Public Health System such as the Cuban one, appropriate measures should be taken to monitor and control morbidity and complications in pregnant diabetic women

The relationship of TNF-? and insulin resistance in patients with Gestational diabetes mellitus / 中国免疫学杂志

Objective:To investigate the relationship between TNF-? and insulin resistance in GDM.Methods:To observe the changes of TNF-?, FBS, FINS and reproductive hormones during early and late gestation in normal group and GDM group.Results:The levels of TNF-?、HOMA-IR in late gestation of both groups are markedly higher than that in early gestation (P0.05).Conclusion:TNF-? is a major factor to effect the insulin resistance.