The long range goal of this research project is to examine the relationship between maternal metabolism and fetal/placental growth.
The specific aims of this research project are: 1) to evaluate the affect of maternal glucose and amino acid insulin sensitivity on fetal/placental growth and development, 2) to determine if neonatal growth and carbohydrate metabolism during the first year of life reflect the effect of """"""""metabolic imprinting"""""""" in utero and 3) to explore the role of alteration in glucose transporters as a potential mechanism for the changes in maternal insulin sensitivity and placental glucose transport capacity. We plan to achieve the first specific aim by longitudinally evaluating amino acid and glucose insulin sensitivity in mid and late gestation in 12 women with gestational diabetes, matched with 12 women with intrauterine growth retarded fetuses and 12 control women. All subjects will be evaluated using: 1) intravenous glucose tolerance test, 2) hydrodensitometry, 3) the hyperinsulinemic-euglycemic clamp coupled with infusion of 2H2 glucose, 1-13C leucine and 2H5 phenylalanine and 4) indirect calorimetry. The specific methodology employed will allow evaluation of 1) insulin response, 2) maternal body composition, 3) basal glucose and amino acid turnover, 4) glucose and amino acid insulin sensitivity during infusion of insulin and 5) the route of glucose disposal. We plan to achieve the second specific aim by: 1) correlating the changes in maternal metabolism with neonatal growth and 2) in these same infants to follow the changes in body composition and islet cell response during the first year of life. Thirty-six neonates will be evaluated using neonatal anthropometric measurements, total body electrical conductivity (TOBEC) and insulin response to an oral glucose challenge. This will allow us to evaluate the longitudinal changes in body composition and insulin response in neonates with a wide range of birthweight and body fat at birth. The third specific aim of this proposal will correlate maternal glucose insulin sensitivity with glucose transporters m-RNA. Ten women will have hyperinsulinemic-euglycemic clamps coupled with 2H2 glucose infusions the day prior to elective cesarean section. At the time of cesarean section, maternal muscle and fat biopsies as well as, placental biopsies will be obtained for glucose transporter m-RNA. The information obtained from these studies will provide us with the information to develop methodologies to diagnose better and treat disorders of maternal metabolism that affect fetal growth.
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