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.
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