【作者】 孙颖；

【导师】 王建华；

【作者基本信息】 天津医科大学 ， 流行病与卫生统计学， 2002， 硕士

【摘要】 目的 妊娠糖尿病(gestational diabetes mellitus，GDM)是孕妇中最为常见的代谢异常，可累及1％-5％的孕妇，是对母婴健康均有严重危害的高危妊娠。GDM患者在产后血糖虽可逐渐恢复正常，但未来10年中有30％-50％的妇女可发展成糖尿病，并且围产儿患病率及死亡率都高于正常妊娠。通过口服糖耐量试验(OGTT)可区分糖耐量减低(IGT)及GDM，本文通过对IGT和GDM——妊娠期高血糖的筛查，探讨妊娠期高血糖在塘沽地区的发病率及其相关危险因素；并通过病例对照研究初步探讨妊娠期高血糖与细胞毒性T淋巴细胞相关抗原4基因(CTLA4)多态性之间的关系。 方法 本文采用筛查方法对天津市塘沽地区自2000年11月至2002年3月期间接受产前健康检查的孕妇进行流行病学问卷调查，获得调查对象的人口统计学特征及相关危险因素，并测量身高、体重、腰围、50gl-hGCT及75g2-h OGTT血糖值等指标。所有孕妇于24～28周进行50g葡萄糖激发试验(GCT)，1小时血糖值≥7.8mmol／L者，继续进行75g口服葡萄糖耐量试验(OGTT)，按WHO标准2小时血糖值在7.8mmol／L和11.1mmol／L之间者为ICT，2小时血糖值≥11.1mmol／L者即确诊为GDM。将筛查出的IGT和GDM作为妊娠期高血糖病例，用非条件Logistic回归分析探讨妊娠期高血糖在本地区潜在的危险因素：并以塘沽及市区共计33名妊娠期高血糖患者为病例组，选取66名正常孕妇为对照组，采集病例和对照组的静脉全血，抗凝、冷冻保存，运用PCR-RFLP实验室技术对CTLA4启动子和外显子1的2个突变位点进行检测，初步探讨其与妊娠期高血糖关系。 结果1．非条件LOgistiC 回归单因素分析显示：孕前洲IOJ．667， 95％CI：l．567～37．514）、首诊WHR①R＝2．794，95MI：l．235～6．318）、孕 妇高血压疾病史（OR＝1．317，95MI：l．060～1．635）、大手术史（OR＝12．050， 95％CI：3．797～38．24）、不明原因死胎史（OR＝1．881，95％CI：l．177～3．007）、 申 首诊体重（OR二3．471，95％CI：1．06～11．367）、孕妇年龄（OR二2．533，95％CI： 1．079～5．947）、首诊股围（OR＝3．949，95％CI：1．307～11．929）、油脂摄入 （OR＝3．252，95％CI：l．606～6．586）共9个变量与妊娠高血糖的发生相关。 调整混杂因素后，孕前驯、首诊硼R、孕妇高血压疾病史和大手术史4个 变量增加妊娠高血糖发生的危险性依然存在；随初孕年龄的增加、有糖尿病 家族史，妊娠高血糖的发病率随之增高，但无统计学显著性：未见筛查人群 的生活习性、家庭因素、个性特征等对妊娠高血糖的发生有关联。 2．妊娠高血糖增加了妊高症的发生危险性（OR二9．697，95％CI：2．489～ 37．775）；妊娠高血糖增加了生产巨大儿（340009）的危险性（OR＝4．254， 95％CI：1．389～13．026），并均具有统计学显著性。 3．病例对照研究结果显示CTLA4 49A—G突变增加妊娠高血糖发生的危 险性，OR＝2．914，95％CI＝1．478～5．743。基因型 AG与 AA组相比 OR＝3．127， 95％CI＝1．513～6．42；基因型GG与AA组相比OR＝7．815，95％CI＝3．60～15．43， 均有统计学差异，说明随A变异为G程度的增加，发生妊娠期高血糖的危险 性也增加，两者存在剂量反应关系。CTLA4启动子－318位核昔酸C—T变异 增加发生妊娠期高血糖的危险性，OR＝n．605，95忧I＝卫．296～m3．92，有 统计学显著意义。 结论1．非条件LOgistiC回归多因素分析得出孕前BMI、首诊WHR、孕妇高 血压疾病史和大手术史是妊娠期高血糖的独立危险因素。 2．妊娠高血糖孕妇加大了发生妊高症、巨大儿的危险性。 二 3．CTLA4第49位核昔酸A—G变异和CTLA4启动子－318位核昔酸 C—T变异可能增加了妊娠期高血糖的发生危险性。更多还原

【Abstract】 OBJECTIVE Gestational diabetes mellitus (GDM) has been defined as a glucose intolerance of varying severity with onset of first recognition during pregnancy. GDM accounts for 1% to 5% of all pregnancies and is associated with an increased risk of morbidity and mortality. Standardization of oral glucose tolerance tests (OGTT) made it possible to define two different clinical entities: impaired glucose tolerance (IGT) and GDM. So we collect the samples according to WHO criteria of IGT and GDM to investigate the association of risk factors and CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene polymorphism with gestational high glucose.METHODS An epidemiological screening of pregnant women at Commune hospitals in Tanggu District in Tianjin between Nov 2000 and Mar 2002. By using questionnaire to obtain information about demographic characteristics, and then some variables were measured including height, weight, waist circumference and 50g 1-h GCT blood glucose, 75g 2-h OGTT blood glucose and so on. Screening was performed with the 50g 1-hour oral glucose challenge test (GCT) between 24 and 28 weeks of gestation to see if fasting blood sugar (FBS) <7. Ommol/L4Patients with 50g 1-h GCT blood glucose ^7.8mmol/L were taken to undergo a 75g 2-hour oral glucose challenge test (OGTT) after an appropriate 2 days carbohydrate load and overnight fast. According to WHO criteria, the diagnosis of IGT is 7. 8mmol/L to 11. Immol/L and GDM is ^11. Immol/L. We collected the blood samples of 33 cases with IGT\ GDM and 66 controls at the same hospital. We used non-conditional logistic regression to analyze the risk factors of gestational high glucose; The promoter and exon 1 of CTLA4 gene were analyzed by PCR-RFLP to study the association between CTLA4 gene polymorphism and gestational high glucose.RESULTS l.A non-conditional logistic regression analysis showed: pre-pregnancy BMI (OR=7. 667, 95%CI: 1. 567 ?37. 514), WHR at the first examination(OR=2.794, 95%CI : 1.235 ~ 6.318) , history of hypertension(OR=1.317, 95%CI : 1.06 ~ 1.635) , history of operation(OR=12. 050, 95%CI: 3. 797?8. 24) and so on, nine variables were associated statistically with gestational high glucose. After adjusting for pre-pregnancy BMK WHR at the first examination, history of hypertension, history of operation, the results showed that they still increased the risk of gestational high glucose; Risk for developing gestational high glucose was increasing with first gestational age and family history of DM, but there were no statistical significance. Other patients’ conditions were not associated with gestational high glucose.2. The difference of gestational hypertension syndrome and macrosomia ( ^4000g) between two groups is statistically significant (OR=9. 697,95%CI: 2.489?7.775 and OR=4. 254, 95%CI: 1.389?3.026) . 3. CTLA4 49A-籊 polymorphism of the genotype were A/G and G/G, differed significantly from those of normal controls OR =2. 914, 95% CI=1. 478?5. 743; the same as the C桾 transition polymorphism of the CTLA4 gene promotor OR =11.605, 95% 01=1.296?03.92, genotype was C/T only.CONCLUSION LA non-conditional logistic regression multivariate analysis showed: pre-pregnancy BMI, WHR at the first examination, history of hypertension, history of operation were independent risk factors for gestational high glucose.2. Hypertension syndrome during pregnancy and macrosomia have been increased in women with gestational high glucose.3. This study demonstrates that CTLA4 49 G allele and CTLA4 promotor C桾 mutation may be associated with gestational high glucose.更多还原