The long term objective of the Program Project Grant Diabetes in Pregnancy III, is to decrease maternal & mortality in diabetic pregnancy. The major theses is that maternal glucose control & reduction of fetal hyperinsulinism reduce metabolic & functional disturbances in mother & fetus. Section A Drs. Miodovnik, Berk, Ballard, Dignan, & Tsong conduct a core clinical trial: continuing a unique prospective randomized trial of strict glycemic control vs less strict control, beginning in the first 9 weeks vs late entry, & a control group. The thesis is: strict early control reduces maternal complications, early fetal loss, malformations, & neonatal morbidity & mortality. A 1) Drs. Berk & Miodovnik test the thesis: impaired adrenergic conterregulatory response to hypoglycemic increases frequency & severity of hypoglycemia in pregnancy; strict glycemic control results in frequent & severe hypoglycemia & impaired adrenergic counferregulation. A2) Drs. Sperling, Mimouni & Compaigne test the thesis: hyperplastic fetal islets results in long term insulin hyperresponsiveness to secretagogues including glucose; & persistent hyperinsulinemic responsiveness induces insulin resistance. A3) Drs. Mimouni, Tsang & Ross test the thesis: maternal diabetic magnesium deficiency may result in neon(ital hypoporathyroidism, magnesium administration in infants results in higher magnesium, parathyroid & calcium, but similar 1,25(OH)2 D. A4) Drs. Berk & Lipman will study the short & long-term consequences of pregnancy on diabetic microvascular complications. Section B Dr. Richardus Ross directs a core alloxan diabetic pregnant sheep model. B1) Drs. Ross, Mimouni & Tsong test the thesis that maternal 1,25-vitamin D production is impaired in diabetic pregnancy, leads to decreases in intestinal calcium absorption, bone turnover & placental calcium transfer. Adaptive fetal responses include enhanced 1,25-vitamin D production & decreased bone mineralization. B2) Drs. Whitsett & Korfhagen test the thesis: insulin dependent inhibition of the SP-B gene is cis-active & maps in or near the SAP gene promoter: Clinical sheep studies of SPA & SP-B expression in IDM will provide in vivo correlates of molecular studies. B3) Dr. Cuppoletti tests the thesis: insulin in the fetus: increases glucose transport protein complement & glucose transport in isolated cardiac myocytes; & """"""""triggers"""""""" synthesis of MRNA for new D-glucose carrier proteins. B4) Dr. Sperling will apply the Fick principle & isotope dilution in-normal & diabetic pregnant sheep with catheterized fetal, utero-placental & maternal circulations comparing glucose, fructose & leucine metabolism & their potential contribution to fetal energy & growth. Section C, Drs. Tsong, Sperling, Campaigne & Ms. Gratton provide administrative organization. CI The Core biostatistics group, Drs. Hertzberg & Buncher provide integrated support for all studies. In this PPG,basic & clinical studies complement each other in an integrated, multidisciplinary study.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD011725-14
Application #
3096703
Study Section
Special Emphasis Panel (SRC (SR))
Project Start
1978-06-01
Project End
1993-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
14
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Khoury, Jane C; Dolan, Lawrence M; Vandyke, Rhonda et al. (2012) Fetal development in women with diabetes: imprinting for a life-time? J Matern Fetal Neonatal Med 25:11-4
Vandyke, Rhonda; Ren, Yan; Sucharew, Heidi J et al. (2012) Characterizing maternal glycemic control: a more informative approach using semiparametric regression. J Matern Fetal Neonatal Med 25:15-9
Feghali, Maisa; Khoury, Jane C; Shveiky, David et al. (2012) Association of vaginal delivery efforts with retinal disease in women with type I diabetes. J Matern Fetal Neonatal Med 25:27-31
Feghali, Maisa N; Khoury, Jane C; Timofeev, Julia et al. (2012) Asymmetric large for gestational age newborns in pregnancies complicated by diabetes mellitus: is maternal obesity a culprit? J Matern Fetal Neonatal Med 25:32-5
Khoury, J C; Miodovnik, M; Buncher, C R et al. (2004) Consequences of smoking and caffeine consumption during pregnancy in women with type 1 diabetes. J Matern Fetal Neonatal Med 15:44-50
Kalkwarf, H J; Bell, R C; Khoury, J C et al. (2001) Dietary fiber intakes and insulin requirements in pregnant women with type 1 diabetes. J Am Diet Assoc 101:305-10
Mehta, K C; Kalkwarf, H J; Mimouni, F et al. (1998) Randomized trial of magnesium administration to prevent hypocalcemia in infants of diabetic mothers. J Perinatol 18:352-6
Namgung, R; Tsang, R C; Lee, C et al. (1998) Low total body bone mineral content and high bone resorption in Korean winter-born versus summer-born newborn infants. J Pediatr 132:421-5
Rosenn, B M; Miodovnik, M; Khoury, J C et al. (1997) Deficient counterregulation: a possible risk factor for excessive fetal growth in IDDM pregnancies. Diabetes Care 20:872-4
Bainbridge, R R; Mimouni, F B; Landi, T et al. (1996) Effect of rice cereal feedings on bone mineralization and calcium homeostasis in cow milk formula fed infants. J Am Coll Nutr 15:383-8

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