. Hyperglycemia is frequently encountered when sick newborn infants receive TPN providing glucose exceeding the infant normal glucose turnover rate. Recent studies in critically ill children and adults have demonstrated that hyperglycemia was associated with increased mortality. Since sick newborns, particularly those with very low birth weight also constitute a high-risk population, preventing hyperglycemia without compromising their energy intake, may reduce their risk of an adverse outcome. To accomplish this goal requires detailed knowledge about potential factors involved in the development of hyperglycemia (regulation of glucose production, gluconeogenesis, glycogenolysis, glucose utilization;and insulin secretion and insulin resistance), and the mechanisms by which e.g. insulin infusion and reduced glucose infusion rates affect glucose metabolism to reduce blood glucose. These issues will be addressed by the protocols described in this revised competing renewal grant proposal. The following hypotheses will be tested in 75 ELBW (Extremely Low Birth Weight) infants during a 5 y period: 1. Rates of gluconeogenesis do not change in response to a decrease in concentrations of glucose and insulin resulting from a reduction of the rate of glucose infusion to 3 mg/kg min;2. Infusion of insulin will a) not acutely suppress rates of gluconeogenesis;b) increase glucose utilization in proportion to body weight;c) increase protein synthesis;3. In infants receiving standard TPN, hyperglycemia is primarily a result of insufficient insulin secretion. These studies will improve our insight into the regulation of glucose production, gluconeogenesis and glycogenolysis;the pathophysiology of hyperglycemia and the mechanisms by which insulin infusion affects glucose and protein metabolism. A clear understanding of the mechanisms that control glucose homeostasis in the extremely low birth weight infant will permit us to develop evidence based strategies to maintain euglycemia while providing appropriate energy intake.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD037957-09
Application #
7575191
Study Section
Pregnancy and Neonatology Study Section (PN)
Program Officer
Grave, Gilman D
Project Start
2000-04-01
Project End
2011-02-28
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
9
Fiscal Year
2009
Total Cost
$213,249
Indirect Cost
Name
Baylor College of Medicine
Department
Pediatrics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Chung, Stephanie T; Chacko, Shaji K; Sunehag, Agneta L et al. (2015) Measurements of Gluconeogenesis and Glycogenolysis: A Methodological Review. Diabetes 64:3996-4010
Chacko, Shaji K; Ordonez, Jorge; Sauer, Pieter J J et al. (2011) Gluconeogenesis is not regulated by either glucose or insulin in extremely low birth weight infants receiving total parenteral nutrition. J Pediatr 158:891-6
Kaplan, Walid; Sunehag, Agneta L; Dao, Harry et al. (2008) Short-term effects of recombinant human growth hormone and feeding on gluconeogenesis in humans. Metabolism 57:725-32
Chacko, Shaji K; Sunehag, Agneta L; Sharma, Susan et al. (2008) Measurement of gluconeogenesis using glucose fragments and mass spectrometry after ingestion of deuterium oxide. J Appl Physiol 104:944-51
Hays, Stephane P; Smith, E O'Brian; Sunehag, Agneta L (2006) Hyperglycemia is a risk factor for early death and morbidity in extremely low birth-weight infants. Pediatrics 118:1811-8
Hertel, Paula M; Chacko, Shaji K; Pal, Sunita et al. (2006) Subcutaneous infusion and capillary ""finger stick"" sampling of stable isotope tracer in metabolic studies. Pediatr Res 60:597-601
Tigas, Stelios K; Sunehag, Agneta L; Haymond, Morey W (2002) Impact of duration of infusion and choice of isotope label on isotope recycling in glucose homeostasis. Diabetes 51:3170-5
Sunehag, Agneta L; Haymond, Morey W (2002) Splanchnic galactose extraction is regulated by coingestion of glucose in humans. Metabolism 51:827-32