小于胎龄儿大鼠胰岛素抵抗与ghrelin水平的关系

目的 观察小于胎龄儿(SGA)大鼠胰岛素敏感指数和ghrelin水平的变化及相关关系;探讨ghrelin在SGA导致胰岛素抵抗过程中的作用和意义.方法 采用SD大鼠母鼠妊娠期饥饿法建立SGA大鼠模型,按生后第4周身长和(或)体质量的差异分为有生长追赶组(S1组,n=26)、无生长追赶组(S2组,n=31);以自由饮水及自由进食母鼠娩出之雄性鼠仔为正常对照组(C组,n=27).各组大鼠4周龄时测定体质量及血ghrelin水平,12周龄测定体质量及血ghrelin、空腹血糖、空腹胰岛素并计算胰岛素敏感指数,分析各指标之间的相关性.结果 12周龄SGA大鼠胰岛素敏感指数较C组下降(S1组:2.00±0.58,S2组:2.23±0.58比C组:3.17±0.54,均P＜0.05);血ghrelin水平较C组下降,但差异无统计学意义[S1组:(1.357±0.548)μg/L,S2组:(1.428±0.714)μg/L比C组:(1.843±0.459)μg/L,均P＞0.05].12周龄大鼠血ghrelin水平与空腹血胰岛素水平呈负相关(r=-0.836,P＜0.01),而与胰岛素敏感指数呈正相关(r=0.810,P＜0.01).结论 成年SGA大鼠血ghrelin水平降低与胰岛素抵抗有关,低ghrelin水平可能是胰岛素抵抗的结果.     

孕前体重指数、孕期体重增加与新生儿窒息发生率的关系

目的：探讨孕前体重指数、孕期体重增加量与新生儿窒息发生率的关系。方法：对2012年1月至2014年1月在我院参加孕前检查且分娩单胎活产儿的1522例孕产妇,其中新生儿窒息182例(11.96%),按孕前体重指数分为偏瘦组(BMI<18.5)、正常组(18.5≤BMI<24.0)、超重组(24.0≤BMI<28.0)、肥胖组(BMI≥28),按孕期体重增加分为<0.3 kg/周组、0.3~0.5kg/周组、>0.5 kg/周组,回顾性分析新生儿窒息发生率与孕妇孕前体重指数、孕期体重增加的关系。结果：偏瘦组(BMI<18.5)、正常组(18.5≤BMI<24.0)、超重组(24.0≤BMI<28.0)、肥胖组(BMI≥28)的新生儿窒息的发生率分别是10.60%、11.30%、16.10%、26.83%,呈逐渐递增的趋势;孕期增加体重<0.3 kg/周组、0.3~0.5 kg/周组、>0.5 kg/周组的新生儿窒息率分别为17.81%、11.41%、10.36%,随着孕期增重的增加,新生儿窒息率随之下降。结论：孕妇孕前体重指数(BMI)、孕期体重增加是新生儿窒息发生的重要影响因素,临床上应对孕妇孕前体重指数及孕期体重增加量进行监测,充分评估新生儿发生窒息的危险性,并及早行干预措施,降低新生儿窒息发生率,最大程度保障母婴安全。     

Effect of chorionic villus sampling on utilization of prenatal diagnosis in women of advanced maternal age

The effect of the introduction of chorionic villus sampling on the utilization rate of prenatal diagnosis in advanced maternal age was studied during the period 1 January 1985-1 January 1991. On the first of January 1985, the age limit for prenatal diagnosis in The Netherlands was lowered from 38 to 36 years of age. The overall uptake rate during the studied period increased significantly, but only because of the increased uptake rate in the group 36 and 37 years. In the maternal age group of 42 years and older, an uptake rate as low as 15.9% was established. This was mainly determined by the relatively high percentage (73.0%) of women from ethnic minorities in this age group. The number of CVS procedures increased significantly during the study period, but the utilization rate was not influenced, since the number of amniocenteses decreased accordingly. An increase in acceptability of prenatal diagnosis by women of advanced maternal age due to early testing and early termination of pregnancy could not be substantiated in the present study.     

Obesity in older mothers,gestational weight gain,and risk estimates for preterm phenotypes

Objective

To assess whether advanced maternal age modifies the relationship between maternal pregravid weight status, gestational weight gain patterns, and the occurrence of spontaneous preterm birth (SPB) and medically indicated preterm birth (MIPB).

Methods

Retrospective cohort analysis of vital statistics data from the state of Florida for the period 2004 through 2007 comprising 311,422 singleton pregnancies (two age groups: 20–24 years old or younger women and ≥35 years or older women). Mothers were classified into five clusters based on their pre-pregnancy body mass index (BMI) values: non-obese (less than 30), class I obese (30.0 ≤ BMI ≤ 34.9), class II obese (35.0 ≤ BMI ≤ 39.9), class III obese (40 ≤ BMI ≤ 49.9), and super-obese (BMI ≥ 50.0).

Results

MIPB occurred more frequently among older than younger women [11.8% vs. 6.4%, respectively (p < 0.0001)) whereas SPB occurred more frequently among younger women [11.3% vs. 10.5%, respectively (p < 0.0001)). Maternal obesity increased the risk for MIPB but not for SPB. Regardless of BMI status, the risk of MIPB was elevated among older mothers, particularly among those with suboptimal (<0.23 kg/week) and supraoptimal (>0.68 kg/week) gestational weight gain. A dose–response relationship with increasing gestational weight gain was evident (p < 0.01); the greatest risk for MIPB occurred among older mothers with weekly gestational weight gain in excess of 0.79 kg (OR = 7.76, 95% CI = 5.73–10.5).

Conclusion

The occurrence of medically indicated preterm birth is positively associated with increased maternal pregravid body weight, older maternal age and extremes of gestational weight gain. Targeted pre- and inter-conception weight management efforts should be particularly encouraged in older mothers.     

The relation between birth weight and insulin resistance in Korean adolescents

Low birth weight is associated with insulin resistance and type 2 diabetes in adults. The fetal programming hypothesis has shown that insulin resistance and its associated metabolic disturbances result from a poor gestational environment, for which low birth weight is a surrogate. An at-home questionnaire survey was performed on 660 middle school students (12-15 years) in Seoul, Korea, and 152 cases were randomly selected based on their birth weight. Subjects were divided into three groups according to birth weight. We recorded their birth weight and measured their current anthropometric data, blood pressure, lipid profile, HOMA-IR, and HOMA-beta, and compared these parameters among the groups. The relation of birth weight to physiological characteristics in adolescence was examined. Systolic blood pressure, lipid profiles, and fasting plasma glucose, HOMA-beta were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C-peptide, and HOMA-IR were higher in the lower birth weight tertile. After adjustment for confounding factors, birth weight was inversely related to diastolic blood pressure, insulin, C-peptide, and HOMA-IR. We conclude that low birth weight may predict the risk of the insulin resistance and its progression over age, and that adequate gestational nutrition is therefore necessary to prevent low birth weight.     

妊娠高血压综合征尿蛋白和孕龄对新生儿出生体重影响的研究

目的几乎没有研究报道妊娠高血压综合征(妊高征)患者尿蛋白、孕龄对新生儿出生体重影响的关系,本研究欲探讨各种变化因素对妊高征患者新生儿出生体重影响的量化关系.方法 1997年1月～2004年6月期间,在我院住院分娩患中、重度妊高征产妇136例,对新生儿出生体重与各种因素进行单变量和多变量回归分析.结果单变量回归分析尿蛋白、孕龄分别与新生儿出生体重有高度显著性关系(P＜0.001);尿蛋白和孕龄一起进入多元回归分析,校正影响因素,尿蛋白和孕龄仍然是影响新生儿出生体重显著性因素(P＜0.001),并且每增加一个等级尿蛋白,新生儿出生体重降低241.92g (95%CI:144.77～339.07);孕龄每增加一天,新生儿出生体重增加20.1g(95%CI:13.70～26.50).结论妊高征患者尿蛋白丢失将严重影响新生儿出生体重,孕龄的延长有增加新生儿出生体重.     

无生长追赶SGA幼鼠生长激素和胰岛素受体后信号交联对话的研究

目的：在生长激素（GH）和胰岛素（INS）共享受体后PI3K通路基础上探讨无生长追赶的出生低体重（NCU-SGA）幼鼠GH和INS抵抗的受体后机制，以及2者受体后信号通路的交联对话（cross-talk）。方法:取4周龄NCU-SGA雄性大鼠，采用Western印记及免疫共沉淀技术分别测定NCU-SGA幼鼠在基础状态下、胰岛素激发以及先给予GH受体后信号通路JAK2阻滞剂AG490后再行胰岛素激发后（AG490+INS组）肝组织胰岛素受体底物-1（IRS-1）及其下游信号磷酸化Akt(p-Akt)的表达。结果:（1）IRS-1信号表达： SGA鼠基础状态、INS激发后和AG490+INS组，3组间的IRS-1总蛋白及IRS-1磷酸化水平与正常对照组（C组）无显著差异（P＞0.05）。（2）p-Akt信号表达： C组基础状态时无p-Akt信号表达，INS刺激后表达明显增强。SGA鼠基础状态时p-Akt已有显著表达（慢性激活），INS刺激后表达较基础状态增加，但增殖显著低于正常对照组（P＜0.01）；AG490+INS组的p-Akt较JAK2未被阻断时明显增强（P＜0.01），但仍显著低于正常对照组（P＜0.01)，提示GH的信号干扰了INS受体后IRS-1至Akt的信号转导。结论:NCU-SGA幼鼠INS抵抗的发生与IRS-1-Akt通路受损有关，GH抵抗经GH和INS 2者受体后信号通路间的交联对话（cross-talk）使IRS-1至Akt间的信号转导解偶联,诱导和加重了INS抵抗；而PI3K-Akt可能是发生该解偶联的主要交汇点。     

大于胎龄儿脐血脂联素水平测定及其临床意义研究

目的探讨血脂联素水平与大于胎龄儿发生的关系。方法研究对象为大于胎龄儿和适于胎龄儿各30例。应用酶联免疫吸附法(ELISA)测定脐血和产妇血脂联素浓度,用免疫比浊法测定甘油三酯(TG)、总胆固醇(TCH)、低密度脂蛋白-胆固醇(LDL-c)、高密度脂蛋白-胆固醇(HDL-c)的水平;并分析脐血脂联素水平与母血脂联素、新生儿性别、出生体重、体重指数、胎盘重量和血脂水平的相关性。结果①大于胎龄儿脐血浆脂联素水平低于适于胎龄儿,差异有非常显著性(P<0.01=;大于胎龄儿血TG、TCH、LDL-c、HDL-c的水平与适于胎龄儿比较差异均无显著性(P>0.05)。②大于胎龄儿血浆脂联素水平与新生儿出生体重、BM I、胎盘重量、脐血TG水平均呈显著负相关(r分别=-0.848、-0.785、-0.835,P均<0.001=,与母血脂联素水平、新生儿身长、孕前和分娩时产妇体重及其BM I、其它脐血脂成分无相关性(P>0.05)。母血脂联素水平与上述因素无相关性(P>0.05)③大于胎龄儿男婴和女婴脐血浆脂联素、血脂各成分水平比较差异均无显著性(P>0.05)。结论血脂联素水平的变化与大于胎龄儿的发生有关,测定脐血脂联素水平有助于判断大于胎龄儿的发展趋势,为早期预防糖尿病、心血管疾病等多种肥胖相关性疾病的发生开拓新的思路。     

高脂饲料诱导的大鼠胰岛素抵抗及其与血清瘦素的关系

摄入大量脂肪被认为是胰岛素抵抗（insulin resistance,IR)形成的一个主要因素，本工作根据Storlien LH的配方制作高脂饲料，分别喂饲成年雄性SD大鼠30d和／或60d，用Kraegen EW方法建立正糖钳技术评估IR，观察IR形成和发展过程中基础血清瘦素和胰岛素刺激下血清瘦素的变化。结果喂饲大鼠高脂饲料30d形成IR，其血糖，血清瘦素水平，肩胛区脂肪、肾周脂肪、附睾脂肪垫重量均较对照组显著升高（均P＜0．01），但血清胰岛素水平与对照组比较无差别；喂饲大鼠高脂饲料60d,IR程度和高血糖水平与30d高脂组仍一样，血清瘦素水平和三处脂肪重量进一步升高（P＜0．001和0．01），出现高胰岛素血症（P＜0．05）；但喂饲高脂30和60天动物体重增长和正糖钳实验中灌流胰岛素2h后的血清瘦素水平与对照组无差别。结果：提示高脂饲料可诱导正常成年大鼠形成IR，体脂增高，高血糖，高瘦素血症是这类IR大鼠的特征，而高瘦素血症可能是IR形成的原因，而高胰岛素血症是IR的结果。     

新生儿先天性甲状腺功能异常发病率与胎龄、出生体重关系的研究

目的探讨广西地区先天性甲状腺功能异常（包括先天性甲状腺功能减低症（CH）和高TSH血症）发病率与胎龄、出生体重的关系。方法对2009年9月～2010年12月广西新生儿疾病筛查中心筛查的新生儿,凡滤纸血促甲状腺素（TSH）〉8.0mIU/L者予以召回,进行甲状腺功能检查。结果 2009年9月～2010年12月共筛查220 844人,确诊先天性甲状腺功能异常200人,发病率为1/1104。其中,早产儿（胎龄〈37周）发病率为1/449,足月儿（37≤胎龄≤42周）发病率为1/1189,过期产儿（胎龄〉42周）发病率为1/206,过期产儿发病率高于早产儿及足月产儿（P〈0.05）。低出生体重儿﹙〈2500g）发病率为1/407,正常体重儿（2500～4000g）发病率为1/1236,巨大儿（〉4000g）发病率为1/376,低出生体重儿及巨大儿的先天性甲状腺功能异常发病率明显高于正常体重儿（P〈0.01）。结论先天性甲状腺功能异常的发病率与胎龄、出生体重密切相关,过期产儿、巨大儿、低出生体重儿的发病率较高。注意孕期保健防止过期产儿、巨大儿、低出生体重儿,对降低先天性甲状腺功能异常的发生有重大意义。     

Physiological and pathophysiological regulation of regional adipose tissue in the development of insulin resistance and type 2 diabetes

Aim: To survey the latest state of knowledge concerning the regulation of regional adipocytes and their role in the development of insulin resistance and type 2 diabetes. Methods: Data from the English‐language literature on regional adipocytes, including abdominal, intramyocellular, intrahepatic and intra‐islet fat as well as the adipokines and their relations to insulin resistance and type 2 diabetes, were reviewed. Results: It is not the total amount of fat but the fat that resides within skeletal muscle cell (intramyocellular fat), hepatocytes and intra‐abdominally (visceral fat), via systemic and local secretion of several adipokines, that influences insulin resistance. Among the adipokines that relate to insulin resistance, adiponectin and leptin appear to have clinical relevance to human insulin resistance and others may also contribute, but their role is still inconclusive. The intra‐islet fat also adversely affects β‐cell function and number (β‐cell apoptosis), eventually leading to deterioration of glucose tolerance. The abnormal location of fat observed in patients with type 2 diabetes and their relatives is conceivably partly the results of the genetically determined, impaired mitochondrial fatty acid oxidative capacity. Restriction or elimination of the fat load by weight control, regular exercise and thiazolidinediones has been shown to improve insulin resistance and β‐cell function and to delay the development of type 2 diabetes. Conclusion: These data support the plausibility of an essential role of regional adipose tissue in the development of insulin resistance and type 2 diabetes.     

Plasma leptin and insulin in C57Bl/6J mice on a high-fat diet: relation to subsequent changes in body weight

It has been proposed that leptin and insulin through central effects are involved in the regulation of energy balance and body weight. Whether circulating leptin or insulin levels predict subsequent changes in body weight is, however, not known. We examined plasma leptin and insulin at 2, 3, 6, 9 and 12 months of age in C57Bl/6J mice given a normal diet (n = 12) or a high-fat diet (58% fat on a caloric base; n = 15). Plasma leptin levels increased by age and correlated with body weight in the entire material (r = 0.81, P < 0.001). Also plasma insulin increased by high-fat diet and correlated across all age periods with body weight (r = 0.56, P < 0.001). In mice, given normal diet, plasma leptin or insulin did not correlate to subsequent changes in body weight at any of the time points studied. However, in mice given the high-fat diet, plasma leptin at 6 (r = ?0.57, P = 0.027) and 9 months of age (r = ?0.56, P = 0.042) as well as plasma insulin at 6 (r = ? 0.51, P = 0.049) and 9 months (r = ?0.58, P = 0.037) correlated inversely to the change in body weight during the subsequent 3-month period. Hence, both leptin and insulin are negative predictors for future weight gain in high-fat fed mice. This suggests that when the regulation of body weight is challenged by a high-fat diet, leptin and insulin act to restrain or prevent future weight gain. This in turn may suggest that impairment of these (probably central) actions of leptin and insulin might underlie excessive increase in body weight under such conditions.     

多普勒测定孕妇左心室舒张功能与年龄、心率及胎龄变化的关系

目的运用多普勒及组织多普勒技术测定正常孕妇左心室舒张功能变化,探讨孕妇年龄、胎龄、心率与心功能的关系,为孕产妇早期心功能判断提供帮助。方法选取2009年4月至2010年4月产前检查704例孕妇,年龄19~41岁,平均年龄26.43岁。对所有孕妇进行超声心动图检查,常规检测各项数据,然后分别测定二尖瓣血流频谱及二尖瓣环部组织多普勒频谱。分析孕妇不同年龄、心率及胎龄与左心室舒张功能不全的关系。结果出现血流多普勒异常43例(6.1%),组织多普勒异常152例(21.6%)。随年龄增长、胎龄增长及心率增快,组织多普勒和血流多普勒异常也增多,并且组织多普勒改变比血流多普勒更加明显。结论孕妇怀孕的生理过程相当于心脏功能的负荷试验,使正常衰老过程或病理状态下才出现的舒张功能改变提早出现。并且与孕妇的年龄、胎龄、心率增加有关,这种负荷试验出现的心脏舒张功能异常改变,对孕妇分娩时心功能估计及产后心脏情况评价有积极意义。     

术前碳水化合物对瘢痕切除术后胰岛素抵抗的影响

目的观察术前口服碳水化合物及静脉输注葡萄糖对术后胰岛素抵抗程度的影响.方法择期瘢痕切除术病人60例,随机分为对照组、口服组和静注组,每组20例.术前对照组常规禁食禁饮;口服组口服12.5%碳水化合物的饮料（CHO）;静注组持续静脉输注10%葡萄糖液.分别于口服或静注前、术后6 h采血,测定血糖、血清胰岛素以及红细胞胰岛素受体.结果处理前各组血糖、血清胰岛素、胰岛素敏感指数及红细胞胰岛素高亲和力受体、低亲和力受体无明显差异;术后6 h口服组、静注组的血糖明显低于对照组,与处理前无显著差别;术后6 h各组血清胰岛素无显著差别,均显著高于处理前;胰岛素敏感指数、红细胞低亲和力受体三组均较处理前显著降低,但口服组、静注组明显高于对照组;术后6 h口服组、静注组红细胞高亲和力受体无明显降低;口服组与静注组间的血糖、胰岛素、胰岛素敏感指数及红细胞胰岛素受体无明显差别.结论术前静脉输注葡萄糖可缓解术后胰岛素抵抗的程度,术前饮用碳水化合物具有同样的效果,是一种简单有效的治疗方法.     

选择性PI3K-Akt通路缺陷参与有生长追赶SGA大鼠胰岛素抵抗的发生机制

目的:研究有生长追赶的小于胎龄个体(SGA)骨骼肌组织胰岛素受体后信号分子的变化,探讨其胰岛素抵抗的发生机制。方法:应用孕鼠全程饮食限制法建立SGA大鼠模型。4周龄有生长追赶SGA(CUG-SGA)和无生长追赶SGA(NCUG-SGA)幼鼠随机分为对照组和胰岛素激发组,并设适于胎龄(AGA)组为对照。测定各组血糖和胰岛素(INS)浓度,计算胰岛素抵抗指数(HOMA-IR)和胰岛β细胞功能指数(HOMA-β)。应用Westernblotting测定各组腓肠肌组织胰岛素受体后信号分子胰岛素受体底物1(IRS1)、蛋白激酶B(Akt)和细胞外信号调节激酶(ERK)的表达及其磷酸化情况。结果:(1)CUG-SGA和NCUG-SGA幼鼠INS和HOMA-IR较AGA组明显增高(均P<0.01),CUG-SGA幼鼠的INS和HOMA-IR显著高于NCUG-SGA组。(2)CUG-SGA幼鼠肌肉组织基础状态下已有p-IRS1表达,INS激发后p-IRS1的表达无显著增加;p-Akt的表达在基础状态和INS激发后均较AGA和NCUG-SGA组显著减低;CUG-SGA基础状态亦有p-ERK表达,INS激发后p-ERK表达显著下降。相关分析显示在基础状态和INS激发状态,SGA幼鼠p-Akt与p-ERK表达呈显著负相关(r=-0.737,P<0.05;r=-0.658,P<0.05)。结论:(1)无论追赶与否,SGA个体生后均呈现胰岛素抵抗,CUG-SGA胰岛素抵抗程度更重。(2)IRS1-PI3K-Akt通路受损是胰岛素抵抗发生的重要的受体后机制;该通路阻断的同时发生Ras-MAPK-ERK通路信号的慢性激活,这可能是胰岛素抵抗同时发生生长追赶的分子机制。     

Prolonged preoperative fasting induces postoperative insulin resistance by ER-stress mediated Glut4 down-regulation in skeletal muscles

Preoperative fasting aims to prevent pulmonary aspiration and improve bowel preparation, but it may induce profound systemic catabolic responses that lead to protein breakdown and insulin-resistant hyperglycemia after operation. However, the molecular mechanisms of catabolic reaction induced by prolonged preoperative fasting and surgical stress are undetermined. In this study, anesthetized rats were randomly assigned to receive a sham operation or laparotomy cecectomy. Fasting groups were restricted from food and water for 12 h before operation, while the feeding group had free access to food throughout the study period. Twenty-four hours after operation, the animals were sacrificed to collect blood samples and soleus muscles for analysis. Postoperative blood glucose level was significantly increased in the fasting group with elevated serum insulin and C-peptide. Continuous feeding reduced serum myoglobin and lactate dehydrogenase concentrations. Preoperative fasting activated inositol-requiring transmembrane kinase/endoribonuclease (IRE)-1α and c-Jun N-terminal kinase (JNK) mediated endoplasmic reticulum (ER)-stress, and reduced glucose transporter type 4 (Glut4) expression in the soleus muscle. Phospholamban phosphorylation was reduced and intracellular calcium levels were increased in the isolated skeletal muscle cells. Similar results were found in ER stress-induced C1C12 myoblasts. The expression of Glut4 was suppressed in the stressed C1C12, but was potentiated following inhibition of ER stress and chelation of intracellular free calcium. This study provides evidence demonstrating that prolonged preoperative fasting induces ER stress and generates insulin resistance in the skeletal muscle through suppression of Glut4 and inactivation of Ca²⁺-ATPase, leading to intracellular calcium homeostasis disruption and peripheral insulin resistance.     

原发性高血压患者血清可溶性E选择素水平与胰岛素抵抗的关系

目的:探讨高血压病患者血清可溶性E-选择素(sE-selectin)浓度与胰岛素抵抗、尿酸及血脂的关系。方法:测定186例高血压病患者(男75例,女111例)的空腹血清sE-selectin、血糖、胰岛素、尿酸、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇的浓度,稳态模式评估法计算胰岛素抵抗指数(HOMA-IR)。分析血清sE-selectin浓度与其它各项参数的相关性。结果:以HOMA-IR50%位点,作为判断胰岛素抵抗的切割点,把高血压病患者分为胰岛素抵抗组(IR)与胰岛素敏感组(IS)。男性组血清sE-selectin浓度(50.1±17.8)μg/L显著高于女性组(40.6±16.6)μg/L;男性IR组(51.6±16.8)μg/L与IS组(48.5±18.8)μg/L无显著差异;女性IR组(45.1±18.0)μg/L显著高于IS组(36.0±13.7)μg/L。逐步回归分析显示,男性组HOMA-IR非血清sE-selectin浓度的独立预测因子,但女性组HOMA-IR是血清sE-selectin浓度的独立预测因子;尿酸和血脂均非血清sE-selectin浓度的独立预测因子。结论:女性原发性高血压患者血清sE-selectin浓度与胰岛素抵抗直接相关,男性则无直接相关;尿酸及血脂与血清sE-selectin浓度均无直接相关。