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.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Case Western Reserve University
United States
Zip Code
Koontz, M B; Gunzler, D D; Presley, L et al. (2014) Longitudinal changes in infant body composition: association with childhood obesity. Pediatr Obes 9:e141-4
Kalhan, Satish C; Marczewski, Susan E (2012) Methionine, homocysteine, one carbon metabolism and fetal growth. Rev Endocr Metab Disord 13:109-19
Kim, Jaeyeon; Saidel, Gerald M; Kalhan, Satish C (2008) A computational model of adipose tissue metabolism: evidence for intracellular compartmentation and differential activation of lipases. J Theor Biol 251:523-40
Durnwald, Celeste; Huston-Presley, Larraine; Amini, Saied et al. (2004) Evaluation of body composition of large-for-gestational-age infants of women with gestational diabetes mellitus compared with women with normal glucose tolerance levels. Am J Obstet Gynecol 191:804-8
Okereke, Ndubueze C; Uvena-Celebrezze, Jennifer; Hutson-Presley, Larraine et al. (2002) The effect of gender and gestational diabetes mellitus on cord leptin concentration. Am J Obstet Gynecol 187:798-803
Catalano, P M; Kirwan, J P (2001) Maternal factors that determine neonatal size and body fat. Curr Diab Rep 1:71-7
Uvena-Celebrezze, J; Catalano, P M (2000) The infant of the woman with gestational diabetes mellitus. Clin Obstet Gynecol 43:127-39
Lewy, V D; Danadian, K; Arslanian, S (1999) Determination of body composition in African-American children: validation of bioelectrical impedence with dual energy X-ray absorptiometry. J Pediatr Endocrinol Metab 12:443-8
Catalano, P M; Huston, L; Amini, S B et al. (1999) Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol 180:903-16
Catalano, P M; Thomas, A J; Huston, L P et al. (1998) Effect of maternal metabolism on fetal growth and body composition. Diabetes Care 21 Suppl 2:B85-90

Showing the most recent 10 out of 31 publications