妊娠期糖尿病母儿血清瘦素水平及胎盘瘦素的表达

目的　探讨妊娠期糖尿病 (gestationaldiabetesmellitus ,GDM)母儿血清瘦素水平及胎盘瘦素表达的变化。　方法　采用放射免疫法 (RIA)检测 2 4例GDM母儿和 2 6例正常母儿血清胰岛素和瘦素水平 ,采用逆转录 聚合酶链反应 (RT PCR)技术检测胎盘瘦素mRNA的表达水平。　结果　 (1)GDM组孕妇血清瘦素和胰岛素水平分别为 (18.6 2± 7.86 ) μg/L和 (13.4 7± 5 .11)mIU/L ,对照组分别为 (14 .2 1± 7.5 9) μg/L和 (8.98± 4 .2 3)mIU/L ,两组比较差异有显著性 (P <0 .0 5 )。 (2 )GDM组脐血瘦素和胰岛素水平分别为 (17.93± 6 .14 ) μg/L和 (19.2 6± 6 .73)mIU/L ,对照组分别为 (7.2 7± 4 .32 ) μg/L和 (9.6 7± 4 .89)mIU/L ,两组比较差异有显著性 (P <0 .0 1)。 (3)两组孕妇血清瘦素与胰岛素水平之间无相关关系 (r =0 .2 2 ,P >0 .0 5 ) ,而脐血血清瘦素与胰岛素水平之间呈正相关关系(r =0 .5 3,P <0 .0 1)。 (4 )GDM组胎盘瘦素mRNA表达水平为 (1.92± 0 .0 5 ) ,对照组为 (0 .97± 0 .0 2 ) ,两组比较差异有显著性 (P <0 .0 1)。　结论　胰岛素及瘦素抵抗可能是妊娠期糖尿病的发病原因之一 ,胰岛素对调节胎盘瘦素的表达起重要作用。     

妊娠期糖尿病患者内脏脂肪素表达的变化及其意义

目的:探讨妊娠期糖尿病(GDM)患者内脏脂肪素(visfatin)表达情况及其在GDM发生、发展中的作用.方法:选择106例于2010年10月至2011年3月在天津医科大学第二医院产科行剖宫产术的妇女,收集研究对象临床资料及组织学标本,采用ELISA方法检测血清visfatin水平;RT-PCR方法检测皮下脂肪、大网膜及胎膜组织中visfatin mRNA表达水平.结果:①GDM组血清visfatin水平与妊娠期糖耐量受损(GIGT)组以及正常糖耐量孕妇(NGT)组相比明显升高(P＜0.05),GIGT组血清visfatin水平高于NGT组,差异有统计学意义(P＜0.05).GDM 组皮下脂肪、大网膜及胎膜组织中visfatin mRNA表达水平均高于GIGT组和NGT组,差异有统计学意义(P＜0.01),而GIGT组和NGT组的组织visfatin mRNA表达水平差异无统计学意义(P＞0.05).②以总体为研究对象,血清visfatin水平与皮下脂肪、大网膜及胎膜组织中visfatin mRNA表达水平呈正相关(r=0.24,P=0.045;r =0.53,P=0.001;r=0.15,P=0.049).③血清visfatin水平与HOMA-IR、FINS、TC、TG、孕期体重增加呈正相关(P＜0.05).结论:GDM患者皮下脂肪、大网膜及胎膜组织的visfatin mRNA表达上调,血清visfatin水平升高,与胰岛素抵抗程度有相关性.visfatin可能参与了GDM的发生、发展过程,其水平的检测为研究GDM提供了一个新的视角.     

妊娠期糖尿病孕妇骨骼肌组织胰岛素受体表达及其磷酸化的变化及意义

妊娠期糖尿病（gestational diabetes mellitus，GDM）是一种严重威胁母婴健康的妊娠期代谢紊乱疾病，胰岛素抵抗是GDM的主要发病原因，但发生胰岛素抵抗的分子机制仍不十分清楚。胰岛素受体（insulin receptor，InsR）是胰岛素的特异性结合受体，也是将胰岛素信号导入细胞内的一种关键蛋白，研究表明胰岛素靶组织中InsR的数量、结构及功能的异常与胰岛素抵抗关系密切，[第一段]     

妊娠期糖尿病与血清resistin的关系

妊娠期糖尿病（gestational diabetes mellitus，GDM）是妊娠期首次发生或发现的糖代谢异常，是产妇发展为2型糖尿病的危险因子。有GDM史的女性在产后5年内发生2型糖尿病的危险性为18％～50％^[1]。目前研究认为，GDM发生与胰岛素抵抗状态相关。Resistin是一种富含半胱氨酸的激素，主要由人类脂肪细胞分泌，人类胎盘也有resistin表达，它可削弱脂肪细胞对糖分的摄取，升高血糖，降低胰岛素敏感性。为了解GDM患者分娩前后血清resistin的变化，我们测定了分娩前和分娩后1、3和5天的血清resistin水平。     

妊娠期高血压疾病患者胎盘瘦素的表达及意义

瘦素是肥胖基因的编码产物，主要由脂肪细胞合成和分泌，参与调控机体能量代谢。我们通过研究妊娠期高血压疾病患者胎盘瘦素的表达及其与母血血清、脐血血清瘦素水平和胎儿体重的相关性，以探讨胎盘瘦素在妊娠期高血压疾病发病中的意义及其与胎儿宫内发育的关系。     

妊娠期糖尿病病因学研究

妊娠期糖尿病是指在妊娠期发生或首次发现的不同程度的糖耐量异常。关于其病因,近年来与II型糖尿病相似,本文就遗传、胰岛功能、胰岛素敏感性等方面阐述GDM的发病机制,指出胰岛分泌胰岛素功能下降和胰岛素敏感性的缺陷在GDM患者同时存在且持续至产后,故应对GDM病史产后妇女定期随访糖耐量变化。     

趋化素在妊娠期糖尿病患者血清及胎盘组织中的表达

目的 探讨趋化素(chemerin)在妊娠期糖尿病(GDM)发病中的作用.方法 选择2016年10月至2017年10月在河北省人民医院产科常规产前检查并行择期剖宫产分娩的单胎孕妇共100例,其中GDM组、正常妊娠组(对照组)各50例,采用ELISA法测定孕妇妊娠晚期血清chemerin及肿瘤坏死因子α(TNF-α)的水...     

胎盘生长因子在妊娠期糖尿病患者胎盘中抑制滋养细胞凋亡的作用研究

目的:探讨胎盘生长因子(PLGF)对妊娠期糖尿病(GDM)患者胎盘滋养细胞凋亡的影响。方法:收集20例GDM和20例正常孕妇胎盘组织,采用HE染色法观察GDM患者胎盘组织形态学变化。TUNEL染色以及Caspase-3活性检测胎盘中细胞凋亡情况。Western blot检测胎盘中PLGF蛋白表达情况,免疫组化观察PLGF的原位表达。离体培养人绒毛滋养细胞(HTR-8/SVneo),分为对照组、高糖组(HG)、PLGF+高糖组(PLGF+HG)和PLGF组,应用流式细胞术检测各组HTR-8/SVneo滋养细胞的凋亡率。结果:与对照组相比,GDM患者胎盘中滋养细胞凋亡明显减少,Caspase-3活性明显减弱。PLGF在GDM胎盘中的表达明显高于对照组;高糖诱导HTR-8/SVneo滋养细胞凋亡增加,PLGF预处理明显逆转高糖诱导的HTR-8/SVneo滋养细胞凋亡增加。结论:GDM患者胎盘中滋养细胞凋亡明显减少,而胎盘中PLGF表达升高。离体实验进一步证明PLGF能够抑制高糖所致HTR-8/SVneo滋养细胞凋亡增加,因此PLGF表达升高可能是GDM患者胎盘中滋养细胞凋亡减少的原因。     

妊娠期糖尿病孕妇外周血、脐血及胎盘中的chemerin表达

目的:探讨正常孕妇和妊娠期糖尿病(GDM)患者外周血、脐血以及胎盘中趋化素(chemerin)的表达差异及其临床意义。方法:选取2010年10月至2011年10月上海交通大学医学院附属第一人民医院20例正常孕妇及20例GDM孕妇。应用ELISA法检测外周血及脐血中chemerin水平,Western blot法测定其在胎盘中的表达,并分析其与临床相关特征的关系。结果:chemerin在正常孕妇和GDM孕妇外周血中的表达无显著差异,而在脐血和胎盘中的表达差异显著(P<0.05),与空腹血糖、餐后2h血糖、空腹胰岛素、胰岛素抵抗指数(HOMA-IR)、C反应蛋白(CRP)、胰岛素用量呈正相关(P<0.05)。结论:chemerin是影响GDM的一个独立因素,在GDM孕妇的脐血和胎盘中表达较高,并随着胰岛素用量的增加而表达增多,其可能通过糖代谢途径及炎症反应在GDM的发生发展中起着重要作用。     

妊娠期糖尿病孕妇胎盘中视黄醇结合蛋白4表达与胰岛素抵抗和胰岛素分泌功能的相关性

目的:探讨妊娠期糖尿病(GDM)胎盘组织中视黄醇结合蛋白4(RBP4)表达及其与胰岛素抵抗和分泌功能的关系。方法:收集胎盘组织共79例,其中正常组27例,GDM组52例。GDM组中未使用(GDMA_1组)和使用胰岛素治疗(GDMA_2组)者各26例。免疫组化(IHC)、Western blot、实时荧光定量PCR(qRT-PCR)检测RBP4在胎盘中的定位及其蛋白和mRNA水平表达。用稳态模式胰岛素抵抗指数(HOMA-IR)及胰岛β细胞功能指数(HBCI)分别作为胰岛素抵抗和分泌功能指标,比较3组以上指标的差异。分析RBP4表达水平与HOMA-IR和HBCI的关系。结果:RBP4表达在胎盘合体滋养细胞胞质中。GDM组的RBP4蛋白和mRNA表达均高于正常组(P0.05)。但GDMA_1组和GDMA_2组比较差异无统计学意义(P0.05)。从正常组到GDMA_1组再到GDMA_2组,HOMA-IR增加;GDM组高于正常组(P0.01),但各GDM组间比较差异无统计学意义(P0.05)。从正常组到GDMA_1组再到GDMA_2组,HBCI先升后降;GDMA_2组低于正常组、GDMA_1组(P0.01),但后两组比较差异无统计学意义(P0.05)。GDM组胎盘组织中RBP4蛋白表达水平与HOMA-IR呈正相关(r=0.819,P0.01),与HBCI无相关(r=0.179,P=0.123)。正常组胎盘组织中RBP4蛋白表达水平与HOMA-IR和HBCI均不相关。结论:RBP4由胎盘分泌,通过参与胰岛素抵抗引起GDM发生,尚无明显证据显示与胰岛素的分泌功能有关。     

The significance of blood and salivary oxidative stress markers and chemerin in gestational diabetes mellitus

ObjectiveGestational diabetes mellitus (GDM) is a medical complication of pregnancy. The aim of this study was to evaluate the correlations between the salivary and blood levels of oxidative stress markers and an adipokine chemerin, which play a role in the pathogenesis of GDM.Materials and methodsStudy groups (Control (n = 29), GDM (n = 22)) had been assessed clinically healthy oral hygiene, according to the age range between 25 and 40 years, BMI<30 kg/m2, who were non-smokers and who were not having systemic diseases. GDM was diagnosed using a 100 g OGTT. Saliva samples were collected without stimulation between 08.30 and 10.00 a.m.. Chemerin and TrxR levels were measured by ELISA. Malondialdehyde, sulfhydryl and NO levels were determined by spectrophotometric analysis. Statistical analysis were performed by Shapiro Wilk, Mann Whitney U, Student's t test.ResultsBlood pressure, BMI, and plasma chemerin, salivary chemerin, fasting glucose, LDL, triglyceride, CRP levels in GDM were not different when compared to Control. There were significant differences between Plasma TrxR and HDL levels. Also, significant differences between salivary TrxR and Malondialdehyde levels were observed in GDM.ConclusionIt was concluded that the optimal cut-off points for oxidative stress parameters and chemerin level can be used to distinguish between healthy pregnant and GDM.     

Altered perlecan expression in placental development and gestational diabetes mellitus

The proteoglycan perlecan is involved in cell signaling, regulation of growth factor activity, and maintenance of basement membranes. This study aims to investigate the expression of perlecan during placental development and whether hyperglycemia of gestational diabetes mellitus induces the alteration of perlecan expression in placenta. Immunohistochemistry, immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and quantitative real-time PCR were carried out to study the placental perlecan expression at different trimesters of pregnancies and in gestational diabetes mellitus. The perlecan protein was mainly immunolocalized in the trophoblast and vessel basement membranes with some staining in the villous stroma of placental villus. Perlecan was also found to co-localize with laminin and collagen IV in the basement membranes of placenta. The protein and mRNA levels of placental perlecan were significantly decreased as the gestational age increased. However, a significant increase in perlecan expression was observed in the third trimester placentas with gestational diabetes mellitus compared to the gestational age-matched controls. Furthermore, trophoblast cells cultured in a high glucose (30 mM) medium and a high osmotic pressure medium (5.6 mM glucose and 24.4 mM mannitol) showed increased perlecan expression compared to cells cultured in the low glucose (5.6 mM) regular medium. These alterations of perlecan expression may be associated with the structural changes of placenta during maturation. The metabolic effect of high glucose and high osmotic pressure of gestational diabetes mellitus may contribute to the increased perlecan expression of diabetic placentas.     

Relationship of maternal serum resistin and visfatin levels with gestational diabetes mellitus

Introduction: Adiponectin, resistin and visfatin are thought to play role in the pathophysiology of gestational diabetes (GDM). In this study, we aimed to investigate the association of maternal second trimester serum resistin and visfatin levels with GDM.

Materials and methods: Screening and diagnosis for GDM was performed between the 24–28th gestational weeks. About 40 women diagnosed with GDM and 40 non-diabetic women constituted the study and control groups, respectively. Groups were compared for second trimester maternal serum resistin, visfatin and HbA1c levels, HOMA-IR and postpartum 75?g OGTT results.

Results: Mean serum resistin (p?=?0.071) and visfatin (p?=?0.194) levels were similar between the groups. However, mean BMI (p?=?0.013), HOMA-IR (p?=?0.019), HbA1c (p?p?=?0.037) were significantly higher in GDM group compared to controls. Type 2 diabetes and impaired glucose tolerance were detected in 2 (5%) and 7 (20%) women in the GDM group, respectively, with 75?g OGTT performed at the postpartum 6th week. Resistin levels of patients with GDM and postpartum glucose intolerance were higher than those with GDM but no postpartum glucose intolerance (p?=?0.012). Visfatin levels in the GDM group showed a positive correlation with biparietal diameter, head circumference, abdominal circumference and femur length (p?Conclusion: Maternal serum resistin and visfatin levels are unchanged in GDM. In patients with GDM, second trimester resistin levels may be predictive for postpartum glucose intolerance and second trimester visfatin levels may be related with fetal biometric measurements. Further larger studies are needed.     

妊娠糖尿病胰岛素治疗与围生儿预后

目的 探讨在妊娠糖尿病（GDM）治疗中胰岛素、饮食以及开始治疗时间早晚对围生儿预后的影响。方法 选择诊断为妊娠糖尿病者109例，其中采用饮食加胰岛素治疗22例，单纯饮食控制组低于应用胰岛素组，差异显著（P＜0.05）。围生儿结局显示：巨大儿发生率、红细胞增多症发生率三组为34周后饮食控制组＞34周前饮食控制组＞胰岛素治疗组。结论 GDM要早诊断、早治疗，尤其是应用胰岛素正规治疗对降低围生儿病率、巨大发生率以及控制孕妇血糖水平有重要意义。     

Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a diseases that alters human placenta macro and microvascular reactivity as a result of endothelial dysfunction. The human placenta is a highly vascularized organ which lacks innervation, so blood flux is governed by locally released vasoactive molecules, including the endogenous nucleoside adenosine and the free radical nitric oxide (NO). Altered adenosine metabolism and uptake by the endothelium leads to increased NO synthesis which then turns-off the expression of genes coding for a family of nucleoside membrane transporters belonging to equilibrative nucleoside transporters, particularly isoforms 1 (hENT1) and 2 (hENT2). This mechanism leads to increased extracellular adenosine and, as a consequence, activation of adenosine receptors to further sustain a tonic activation of NO synthesis. This is a phenomenon that seems operative in the placental macro and microvascular endothelium in GDM. We here summarize the findings available in the literature regarding these mechanisms in the human feto-placental circulation. This phenomenon is altered in the feto-placental vasculature, which could be crucial for understanding GDM deleterious effects in fetal growth and development.     

Glycated hemoglobin in pregnancies at increased risk for gestational diabetes mellitus

Objective

The glycated hemoglobin (HbA_1c) value is increasingly used for the detection of (pre)diabetes, but HbA_1c decreases during pregnancy. We sought to identify clinical and metabolic correlates of HbA_1c in pregnancies at increased risk for gestational diabetes mellitus (GDM).

Study design

We prospectively studied 335 gravidas who received a 3-h 100 g oral glucose tolerance test (OGTT) at 24–32 weeks, in most cases after an abnormal glucose challenge test. Several indices of insulin sensitivity and secretion were computed from fasting measurements and the OGTT.

Results

HbA_1c concentrations gradually increased in diet-treated and insulin-treated GDM gravidas compared with non-GDM gravidas. HbA_1c was higher if the insulin peak was delayed until 180 min compared with 60 or 120 min. Stepwise regression identified the homeostasis modeling assessment of insulin resistance (HOMA-IR) as the first-rank correlate. Other correlates were ethnicity, a low insulin-to-glucose response at 60 min, and gestational age. The HbA_1c value corresponding to a fasting glucose of 5.1 mmol/l (diagnostic of GDM) was 2 mmol/mol (∼0.2%) higher if sampling occurred at 29–32 vs. 24–28 weeks or if ancestry was non-European vs. European.

Conclusion

HbA_1c is strongly associated with insulin resistance; in addition, HbA_1c captures the first-phase insulin response. However, HbA_1c varies with gestational age and ethnicity.     

胎盘resistin表达与胎儿出生体重关系的探讨

目的:研究抵抗素(resistin)在孕足月胎盘组织中的表达及与胎儿出生体重的关系。方法:用W estern blot检测孕足月分娩的巨大儿与正常体重新生儿胎盘组织中抵抗素蛋白表达水平并对比其差异。结果:(1)resistin在巨大儿组及对照组胎盘组织中均有表达,巨大儿组胎盘resistin蛋白表达水平为0.82±0.02,在对照组表达水平为0.57±0.06,两组resistin蛋白表达水平差异有统计学意义(P<0.01);(2)胎盘组织中resistin蛋白的表达丰度与新生儿出生体重(r=0.900,P<0.05)呈正相关。结论:resistin蛋白在足月妊娠胎盘组织中有表达,其表达量与新生儿出生体重明显相关,resistin可能是妊娠晚期胎盘中影响胎儿宫内生长的重要因子之一。     

Total plasma homocysteine correlates in women with gestational diabetes

AIM: We aim to assess serum total homocysteine (tHcy) associations with metabolic syndrome components and B-vitamins in women with gestational diabetes mellitus (GDM). METHODS: We studied 61 consecutive pregnant women, 44 with GDM and 17 with normal glucose tolerance (CG). Serum homocysteine levels were analyzed by ELISA, using Bio-Rad reagents. Serum folates and vitamin B(12) concentrations were determined by chemiluminescent immunoassay, free fatty acids (FFA) and lipids enzymatically. RESULTS: Serum homocysteine levels were similar in both the GDM and the CG groups (8 +/- 2.0 vs 7.4 +/- 1.1 mumol/l, respectively). Women with GDM in comparison to CG women were characterized by higher values of homeostasis model of insulin resistance (HOMA-IR) (2.8 +/- 1.7 vs 1.6 +/- 0.9, P < 0.01), serum triglycerides (2.7 +/- 0.9 vs 1.9 +/- 0.5 mmol/l, P < 0.01) and FFA (0.6 +/- 0.2 vs 0.46 +/- 0.2 mmol/l, P < 0.05). In GDM women serum tHcy correlated with vitamin B(12) (r = -0.47, P < 0.01) and folates (r = -0.51, P < 0.001); in CG women with HOMA-IR, a marker of insulin resistance (r = -0.49, P < 0.05). In multiple regression analysis with serum tHcy as a dependent variable, folate and vitamin B(12) entered the analysis in GDM women (beta = -0.42 and -0.34, respectively, P < 0.05), whereas in CG cystatin C and HOMA-IR entered the analysis (P < 0.05). CONCLUSIONS: In women with GDM, serum homocysteine is significantly associated with vitamin B(12) and folate levels, while in healthy pregnant women with HOMA-IR and with kidney function. The results suggest the importance of the B-group vitamins in regulation of serum tHcy levels in women with insulin resistance/gestational diabetes, what might be relevant in protection against pregnancy complications associated with elevated tHcy in GDM women.     

Endocan expression is increased in the placenta from obese women with gestational diabetes mellitus

IntroductionEndocan, a member of the proteoglycan family, is involved in a wide range of diseases including obesity and diabetes. The aim of this study was to determine the effect of (i) maternal obesity and gestational diabetes mellitus (GDM) on placental endocan expression; and (ii) endocan knockdown on markers of inflammation.MethodsEndocan mRNA and protein expression was determined in human placenta from (i) lean and obese and normal glucose tolerant (NGT) pregnant women (n = 10 patients per group); and (ii) women with GDM and BMI-matched NGT women (n = 40 patients per group). Primary villous trophoblast cells and HUVECs were used to assess the effect of endocan siRNA knockdown on pro-inflammatory cytokines.ResultsThere was no effect of maternal obesity on placental endocan expression. Further, endocan expression was not different between lean NGT and BMI-matched women with GDM. However, endocan mRNA and protein expression was significantly higher in placenta from obese women with GDM when compared to BMI-matched NGT women. Knockdown of endocan in villous trophoblast cells and HUVECs had no effect on infection- or inflammation-induced expression and secretion of IL-6, IL-8 and MCP-1.DiscussionEndocan expression is increased in the human placenta from obese women with GDM, and in response to pro-inflammatory stimuli. Loss-of-function studies in villous trophoblast cells and HUVECs revealed that endocan is not directly involved in the genesis or in the expression of pro-inflammatory cytokines induced by LPS or IL-1β. Further studies are required to elucidate the functional consequences of increased placental endocan expression in obese GDM pregnancies.     

糖化血红蛋白在妊娠期糖尿病诊断中的意义

目的:探讨糖化血红蛋白在妊娠期糖尿病(GDM)诊断中的意义。方法:对正常妊娠组44例、糖耐量异常组26例及糖尿病组28例进行空腹血糖(FPG)、糖化血红蛋白(HbAlc)及口服50g葡萄糖筛查试验(GCT)测定。结果:GDM组FPG、GCT、HbAlc较正常妊娠组均显著增高(P<0.05)。正常妊娠组与糖耐量异常组比较,FPG及GCT无差异(P>0.05)。GDM组FPG、GCT、HbAlc阳性率分别为42.9%、89.3%和92.9%。GDM的并发症随HbAlc的增高而增多。结论:HbAlc在妊娠期糖尿病的筛查诊断及并发症的检测方面有一定的意义。