LIPID METABOLISM IN PREGNANCY AND WITH PREECLAMPSIA

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The overall goal of this project is to examine lipid metabolism in women with healthy preeclamptic pregnancies. We will test the hypothesis that women who develop pre-eclampsia have an accentuation of hypertriglyceridemia, beyond the physiologic rise normally found in pregnancy. Hypertriglyceridemia has been associated with pre-eclampsia. Recent studies indicate that elevated triglyceride and FFA can be observed as early as 16 to 20 weeks of pregnancy in women who develop pre-eclampsia. Pregnancy has a pronounced effect on maternal lipid metabolism. The increase in plasma triglyceride during the 2nd and 3rd trimesters is especially striking, increasing approximately 3-fold over first trimester and non-pregnant values. Previous clinical investigations of lipid metabolism during pregnancy have focused on fasting lipid profiles. We propose to extend the study of lipid metabolism during pregnancy to include dynamic responses to meal ingestion. The first of the four protocols we propose will be a longitudinal study of postprandial lipid metabolism in 200 primigravida women at week 16 and again at week 32. Based on an incidence of pre-eclampsia of approximately 5 to 10 percent, we estimate that 10 20 women in this cohort will develop pre-eclampsia. The second protocol will be a study of postprandial lipid metabolism in pregnant women admitted to the "high risk" pregnancy service for pre-eclampsia. The third protocol will be a study of lipolysis, lipid oxidation and triglyceride clearance among postpartum women who had pre-eclamptic pregnancies. The fourth protocol will use insulin infusion/glucose clamp studies to examine insulin resistance in postpartum women who had pre-eclampsia. We will test the hypothesis that abnormalities of postprandial triglyceride metabolism precede and accompany pre-eclampsia, and are associated with enhanced lipolysis, decreased triglyceride catabolism and insulin resistance.