The long range objective of these studies is to document the alterations in maternal and neonatal protein and fat metabolism that may lead to abnormal outcome and place the infant at increased risk for morbidity. Although the effects of maternal diabetes upon the newborn have been known for some time, only recently have the methods for safely quantifying these changes been developed. The proposed studies will utilize the safe stable isotopic tracers with mass spectrometer methods to quantify the aberrations in metabolism and evaluate the intervention strategies. Specifically, nitrogen accretion by the fetus is a systematic process which increases is the gestation advances and decreases during the last few weeks of pregnancy. Therefore, maternal nitrogen/protein metabolism has to adapt with advancing gestation in order to provide for the nitrogen required by the fetus. In the proposed studies maternal protein turnover will be quantified during fasting and in response to feeding. Recent data suggest that in spite of rigorous regulation of maternal metabolism in dia- betic pregnancy, fetal macrosomia persists. In the proposed studies, it is hypothesized that fetal macrosomia in diabetes as well as in obesity may be related to the inability to normalize protein/nitrogen turnover in spite of significant therapeutic effort. This hypothesis will be examined by quantifying leucine metabolism in gestational diabetic pregnancy while under calorie restriction and under insulin therapy. The effects of intermittent fetal hyperglycemia and hyperinsulinemia on protein metabolism will be measured in infants of diabetic mother. We propose that fetal macrosomia in diabetic pregnancy is related to increased nitrogen accretion and will be evident by increased protein synthesis rate. Finally, the contribution of alternate fuels for oxidative metabolism, i.e. fat will be examined in the mother and newborn under clearly defined clinical states. It is anticipated that these studies will improve our understanding of maternal-neonatal metabolism and would result in development of clinical intervention strategies to reduce perinatal morbidity.
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