妊娠期糖尿病导致母胎并发症的基础与临床研究

发布时间：2018-05-19 03:42

本文选题：妊娠期糖尿病 + 维生素D　；参考：《华中科技大学》2015年博士论文

【摘要】：[背景]近年来多项临床研究显示妊娠期糖尿病(GDM)与后代远期心血管和代谢性疾病相关,但是其机制尚不清楚,可能与内皮损伤有关。维生素D缺乏在孕妇中非常普遍并且和GDM风险增高有关。有体外研究显示维生素D可以促进内皮克隆形成细胞(ECFCs)的血管新生功能。因此本研究主要探讨胎儿暴露于糖尿病的环境是否会引起其ECFCs功能紊乱,若出现功能紊乱,并进一步检验维生素D是否可以逆转这种损伤。 [方法】本研究共招募19个健康妊娠孕妇(NP)和18个GDM妊娠孕妇。首先取脐血分离培养外周血单核细胞,记录ECFC克隆首次出现的时间和克隆形成的数量。检测母血和脐血中25-羟基维生素D水平及母血中糖化血红蛋白含量。给予来自NP脐血的第4代ECFCs轻度高糖环境培养7天(对照组培养基糖浓度为5.5mmol/L,实验组糖浓度分别为7,11,15mmol/L)。用第4或5代细胞在添加或不添加10nM维生素D的条件下进行划痕实验和小管形成实验。比较来自GDM和NP的细胞间以及经各种糖浓度处理后的NP细胞间的血管相关功能的差异。最后沉默维生素D受体(VDR siRNA),封闭VDR(P5P)和抑制血管内皮生长因子通路(SU5416)来检验维生素D可能的作用机制。 [结果】来自GDM妊娠的ECFCs的克隆形成数量较少(P=0.04),增殖率降低(P=0.02),迁移修复能力下降(P=0.04),小管形成数量减少(P=0.03)。经高糖培养后的来自NP脐血的ECFCs的迁移修复能力下降(7mM葡萄糖：P=0.04；11mM葡萄糖：P=0.006；15mM葡萄糖：P=0.009),体外血管新生能力也下降(7mM葡萄糖：P=0.045；11mM葡萄糖：P=0.001；15mM葡萄糖：P=0.03),并且这些损伤具有浓度依耐性(迁移修复能力：P0.001；小管形成能力：P=0.004)。添加维生素D可以显著增加来自GDM妊娠或暴露于高糖环境下的ECFCs的迁移修复能力和小管形成能力(P0.05),除15mM葡萄糖处理组外,其余各组均与正常对照组无明显差异。VDR siRNA、P5P或是SU5416处理后的ECFCs的迁移修复能力和血管新生能力均显著下降(P0.05)。添加维生素D后,除了用SU5416处理过的来自GDM的ECFCs的小管形成能力,其余各组ECFCs的迁移修复能力和小管形成能力均显著增加(P0.05)。 [结论]新生儿ECFCs来自GDM或者在体外暴露于高糖环境都有细胞数量的减少和血管相关功能的损伤。即使是轻度的高糖环境培养也对内皮细胞功能造成损伤并可能导致GDM母胎的心血管并发症。VDR沉默和封闭的结果提示维生素D对ECFCs的作用还有非VDR介导的途径。维生素D的保护作用在轻度高糖环境下更有效,这也与大多数GDM妊娠状态一致,因此GDM母亲在孕期保持充足的维生素D水平将有助于改善ECFCs的功能及母胎长远的内皮健康。 [背景]妊娠期糖尿病和糖尿病合并妊娠均与母胎多种不良结局相关。本研究的目的是探讨孕期不同程度的高糖状态是否会导致母胎结局不同,并且分析孕中期糖耐量筛查的血糖值是否可以预测母胎预后。 [方法]本研究为一项回顾性研究,包含从2007年11月至2013年3月在我院住院就诊的383位糖尿病合并妊娠或者妊娠期糖尿病孕妇的临床资料。收集的病人被分为3组：孕前已诊断为糖尿病组(pDM,1型和2型糖尿病),妊娠期糖尿病组(GDM)和孕期诊断为糖尿病合并妊娠组(DM)。收集孕妇基本临床资料、口服糖耐量试验(OGTT)结果、产前随机血糖和母胎并发症情况。用双向逻辑回归方法来评估血糖水平与母胎结局的关系。预测准确性则根据受试者操作特征曲线下面积进行评估。 [结果]pDM和DM两组间除了新生儿重症监护病房(NICU)入住率外,孕妇基本临床资料、其他母胎并发症无明显差异。GDM组的早产发生率、NICU入住率和子痫前期发生率均要显著低于pDM组和DM组(P0.05)。在矫正混杂因素后,OGTTO小时的血糖值可以预测妊娠期高血压(OR=1.24,95%CI[1.04-1.46], P=0.015),早产(OR=1.23,95%CI[1.03-1.47], P=0.025)和死产(OR=1.55,95%CI[1.14-2.10], P=0.005)的发生；产前随机血糖可以预测早产(OR=1.19,95%CI[1.08-1.31],P0.001)和死产(OR=1.41,95%CI[1.17-1.71], P0.001)的发生。 [结论】妊娠期糖尿病孕妇的母胎预后较孕前就有糖尿病的孕妇及孕期发现糖尿病合并妊娠的孕妇要好。无论是孕前还是孕中发现的糖尿病合并妊娠,其结局无明显差别。孕中期OGTT值和产前随机血糖值能够在一定程度上预测妊娠期高血压、早产和死产的发生。
[Abstract]:[background] a number of clinical studies have shown that gestational diabetes (GDM) is associated with long-term cardiovascular and metabolic diseases in future generations, but its mechanism is unclear and may be associated with endothelial damage. Vitamin D deficiency is very common in pregnant women and is associated with a higher risk of GDM. The angiogenesis of cells (ECFCs). Therefore, this study is mainly to explore whether fetal exposure to diabetes can cause ECFCs dysfunction, if dysfunction occurs, and to further examine whether vitamin D can reverse this damage.
[Methods] 19 pregnant women of healthy pregnancy (NP) and 18 pregnant women of GDM pregnancy were recruited. First, umbilical cord blood was isolated and cultured for peripheral blood mononuclear cells. The time of first appearance of ECFC clones and the number of clones were recorded. The levels of 25- hydroxyvitamin D and the content of glycated hemoglobin in the mother blood and the maternal blood were detected. The umbilical blood was given from the umbilical blood of NP. The fourth generation ECFCs mild high glucose environment was cultured for 7 days (the glucose concentration of the control group was 5.5mmol/L, the glucose concentration in the experimental group was 7,11,15mmol/L). The scratch test and the tubule formation experiment were carried out under the conditions of adding or without 10nM vitamin D with the fourth or 5 generation cells. The comparison of the cells from GDM and NP and the N after various glucose concentrations were compared. Differences in vascular related functions between P cells. Finally, silence vitamin D receptor (VDR siRNA), blocking VDR (P5P) and inhibition of vascular endothelial growth factor pathway (SU5416) to test the possible mechanism of vitamin D.
[results] the number of ECFCs clones from GDM pregnancy was less (P=0.04), the proliferation rate decreased (P=0.02), the ability of migration and repair decreased (P=0.04), and the number of tubule formation decreased (P=0.03). The migration and repair ability of ECFCs from NP umbilical blood decreased after high glucose culture (P=0.04; 11mM glucose: P=0.006; glucose: glucose: .009), in vitro angiogenesis also decreased (7mM glucose: P=0.045; 11mM glucose: P=0.001; 15mM glucose: P=0.03), and these injuries have a concentration dependent (migration repair capacity: P0.001; tubule forming ability: P=0.004). Adding vitamin D can significantly increase ECFCs from GDM pregnancy or exposure to high glucose environments The migration and repair ability and the tubule formation ability (P0.05), except for the 15mM glucose treatment group, there was no significant difference between the other groups and the normal control group.VDR siRNA. The migration and repair ability and the angiogenesis ability of ECFCs after P5P or SU5416 treatment were significantly decreased (P0.05). After adding vitamin D, the GDM ECFCs was treated with SU5416. The migration and repair ability and tubule formation ability of ECFCs in other groups increased significantly (P0.05).
[Conclusion] neonatal ECFCs from GDM or exposure to high glucose in vitro has the decrease of cell number and damage of vascular related functions. Even mild high glucose environment culture also causes damage to endothelial cell function and may lead to the.VDR silence and closure of the cardiovascular complications of GDM mothers. The results suggest that vitamin D to ECFCs There is a non VDR mediated pathway. The protective effect of vitamin D is more effective in mild hyperglycemia, which is also in line with most of the GDM pregnancy States, so a sufficient vitamin D level in pregnancy during pregnancy will help to improve the function of ECFCs and the long-term maternal health of the mother fetus.
[background] gestational diabetes and diabetes combined with pregnancy are related to multiple maternal outcomes. The purpose of this study is to explore whether high glucose levels at different levels of pregnancy can lead to different maternal outcomes, and whether the glucose values in the mid-term glucose tolerance screening can predict maternal prognosis.
[Methods] a retrospective study of 383 diabetic patients with gestational or gestational diabetes from November 2007 to March 2013 in our hospital. The patients were divided into 3 groups: pre pregnancy diabetes group (pDM, type 1 and type 2 diabetes), gestational diabetes (GDM) and pregnancy The diagnosis was diabetes combined pregnancy group (DM). Basic clinical data of pregnant women, oral glucose tolerance test (OGTT), prenatal blood glucose and maternal fetal complications were collected. The relationship between blood glucose level and maternal fetal outcome was evaluated by two-way logic regression. The prediction accuracy was evaluated according to the area under the subject operating characteristic curve.
[results] in addition to the occupancy rate of neonatal intensive care unit (NICU) between the two groups of]pDM and DM, the basic clinical data of pregnant women and other maternal complications had no significant difference in the incidence of preterm birth in the.GDM group. The rates of NICU occupancy and preeclampsia were significantly lower than those of the pDM group and the DM group (P0.05). Pregnancy induced hypertension (OR=1.24,95%CI[1.04-1.46], P=0.015), preterm birth (OR=1.23,95%CI[1.03-1.47], P=0.025) and stillbirth (OR=1.55,95%CI[1.14-2.10], P=0.005) were measured; prenatal blood glucose could predict the occurrence of premature birth (OR=1.19,95%CI[1.08-1.31], P0.001) and dead birth (OR=1.41,95%CI[1.17-1.71], P0.001).
[Conclusion] the maternal prognosis of pregnant women with gestational diabetes is better than that of pregnant women who have diabetes and pregnant women during pregnancy. There is no significant difference in the outcome of diabetes and pregnancy found before pregnancy or during pregnancy. The OGTT value in the middle pregnancy and the value of prepartum random blood sugar can predict the high pregnancy period to a certain extent. Blood pressure, preterm birth and stillbirth.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R714.256

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