RELATIONSHIP BETWEEN MATERNAL OBESITY AND PREGNANCY OUTCOME

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。在肥胖妇女中，对怀孕的适应与母亲和胎儿不良并发症的风险增加有关。虽然这种营养不良状况对不良妊娠结局的贡献是公认的，但其对成功妊娠所需的代谢/生理适应的不良影响仍然是未知的。本项目旨在提供一个更好的了解如何产妇肥胖改变葡萄糖代谢，导致妊娠糖尿病，以及它如何改变抗氧化剂-促氧化剂稳态，这可能有助于妊娠高血压。它还将测试旨在减少或纠正这些不良后果的营养疗法。将在肥胖和正常体重孕妇中进行实验，以检验以下假设：1）肥胖妇女因氧化应激而患妊娠期高血压或先兆子痫，并且抗氧化维生素和半胱氨酸的膳食补充剂（刺激谷胱甘肽合成）会降低氧化应激，从而增加妊娠高血压的风险; 2）在有妊娠糖尿病史的肥胖妇女中，适度运动加适当饮食的方案将通过减弱妊娠诱导的胰岛素敏感性降低和肝葡萄糖产生的过度增加以及葡萄糖摄取的降低来减少对低血糖治疗的需要。为了检验假设1，将在诊断时在一组患有PIH或先兆子痫的妊娠肥胖妇女中、在一组年龄和BMI匹配的没有PIH或先兆子痫的妊娠肥胖妇女中（n=10）以及在一组正常体重的妊娠妇女中测量炎症的血浆生物标志物（TNF α、CRP）、氧化剂损伤（δ-异前列烷、氢过氧化物）、抗氧化剂潜力、红细胞GSH合成和GSH：GSSC比率、血压和尿蛋白排泄。同样的测量将在两组有妊高征病史的肥胖孕妇中进行，在补充抗氧化剂或安慰剂20周之前和之后。为了检验假设2，将在妊娠10-12周时和20周后对两组有妊娠糖尿病史的肥胖孕妇进行葡萄糖动力学和胰岛素敏感性测定，这些孕妇接受充足饮食加每日运动或仅充足饮食的方案。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In obese women, adaptation to pregnancy is associated with increased risks for adverse complications to both mother and fetus. Although the contribution of this malnourished condition to poor pregnancy outcome is well-established, its adverse effects on the metabolic/physiologic adaptations necessary for a successful pregnancy remain mostly unknown. The present project aims to provide a better understanding of how maternal obesity alters glucose metabolism to cause gestational diabetes and how it alters anti-oxidant - pro-oxidant homeostatis which may contribute to pregnancy induced hypertension. It will also test nutritional therapies aimed at reducing or correcting these adverse outcomes. Experiments will be performed in obese and normal weight pregnant women to test the following hypotheses: 1) that obese women develop gestational hypertension or preeclampsia because they have oxidative stress and that dietary supplements of antioxidant vitamins and cysteine (to stimulate glutathione synthesis) will decrease oxidative stress, hense the risk of gestational hypertention; 2) that a regimen of moderate exercise plus an adequate diet will decrease the need for hypoglycemic therapy by attennuating the pregnancy-induced decrease in insulin sensitivity and the exaggerated increase in hepatic glucose production and decrease in glucose uptake in the obese woman with ah history of gestational diabetes. To test hypothesis 1, plasma biomarkers of inflammation (TNFa, CRP), oxidant damage (8-isoprostane, hydroperoxides), antioxidant potential, erythrocyte GSH synthesis and GSH:GSSC ration, blood pressure and urinary protein excretion will be measured in a group of pregnant obese woman with PIH or pre-eclampsia at time of diagnosis, in an age- and BMI-matched group (n=10) of pregnant obese women without PIH or preclampsia and in a group of normal weight pregnant women. The same measurements will be made in two groups of obese pregnant women with a history of PIH before and after 20 weeks of supplements of either antioxidants or placebo. To test hypothesis 2, glucose kinetics and insulin sensitivity will be measured in two groups of pregnant obese women with a history of gestational diabetes at weeks 10-12 of pregnancy and after 20 weeks on a regimen of an adequate diet plus daily exercise or just an adequate diet.