The long range goals of my research are: (1) to evaluate the effect of insulin resistance and altered glucose metabolism during pregnancy on fetal growth and development; (2) to develop clinical methodologies to diagnose women with gestational diabetes earlier in gestation; and (3) to test the value of treatment regimens based on the specific underlying metabolic abnormalities.
The specific aims of this research proposal are: (1) to serially evaluate glucose metabolism and insulin resistance before and during pregnancy in lean and obese non-diabetic women; (2) to serially evaluate glucose metabolism and insulin resistance before and during pregnancy in lean and obese gestational diabetics matched for percent body fat, diet, age, parity and level of physical activity. We plan to achieve these initial specific aims by evaluating longitudinally 15 normal women matched with 15 gestational diabetics prior to conception and during early and late gestation. All subject will be evaluated using: (1) the oral glucose tolerance test; (2) the intravenous glucose tolerance test; (3) underwater weighing; (4) islet cell antibodies; and, (5) the hyperinsulinemic-euglycemic clamp with simultaneous indirect calorimetry. The specific methodology employed will allow evaluation of: (1) endogenous glucose production in the basal state and in response to insulin by the infusion of dideuterated glucose as the tracer during the """"""""clamp""""""""; (2) peripheral insulin resistance; (3) the route of glucose disposal whether by oxidative or non-oxidative routes; (4) insulin clearance; (5) glucose disappearance (K value) and 1st and 2nd phase insulin response; (6) the percent body fat; and (7) those women at risk for type 1 diabetes. These studies will resolve controversies in our understanding of insulin resistance and maternal glucose metabolism during gestation in normal and gestational diabetic women. The information obtained from these studies will provide us with the data to develop clinical methodologies to diagnose gestational diabetes earlier in gestation. We then plan to test the value of improved treatment regimens based on the specific metabolic abnormality, to decrease maternal and perinatal morbidity.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HD022965-06
Application #
3469535
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1987-06-02
Project End
1993-05-31
Budget Start
1991-06-01
Budget End
1993-05-31
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Berggren, Erica K; Presley, Larraine; Amini, Saeid B et al. (2015) Are the metabolic changes of pregnancy reversible in the first year postpartum? Diabetologia 58:1561-8
Catalano, P; deMouzon, S H (2015) Maternal obesity and metabolic risk to the offspring: why lifestyle interventions may have not achieved the desired outcomes. Int J Obes (Lond) 39:642-9
Yang, Xiaohua; Haghiac, Maricela; Glazebrook, Patricia et al. (2015) Saturated fatty acids enhance TLR4 immune pathways in human trophoblasts. Hum Reprod 30:2152-9
Lassance, Luciana; Haghiac, Maricela; Minium, Judi et al. (2015) Obesity-induced down-regulation of the mitochondrial translocator protein (TSPO) impairs placental steroid production. J Clin Endocrinol Metab 100:E11-8
Katzmarzyk, P T; Barlow, S; Bouchard, C et al. (2014) An evolving scientific basis for the prevention and treatment of pediatric obesity. Int J Obes (Lond) 38:887-905
Catalano, Patrick M; Mele, Lisa; Landon, Mark B et al. (2014) Inadequate weight gain in overweight and obese pregnant women: what is the effect on fetal growth? Am J Obstet Gynecol 211:137.e1-7
Catalano, P M (2014) Trying to understand gestational diabetes. Diabet Med 31:273-81
Maple-Brown, L J; Roman, N M; Thomas, A et al. (2013) Perinatal factors relating to changes in maternal body fat in late gestation. J Perinatol 33:934-8
Waters, Thaddeus P; Huston-Presley, Larraine; Catalano, Patrick M (2012) Neonatal body composition according to the revised institute of medicine recommendations for maternal weight gain. J Clin Endocrinol Metab 97:3648-54
Basu, Subhabrata; Haghiac, Maricela; Surace, Peter et al. (2011) Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation. Obesity (Silver Spring) 19:476-82

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