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 besed strategies to maintain euglycemia while providingappropriate energy intake.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR007122-19
Application #
7784531
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Sawczuk, Andrea
Project Start
1997-02-14
Project End
2011-08-28
Budget Start
2010-03-01
Budget End
2011-08-28
Support Year
19
Fiscal Year
2010
Total Cost
$3,645,129
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
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