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General Clinical Research Center

全科临床研究中心

基本信息

批准号：
7784531
负责人：
WILLIAM B APPLEGATE
金额：
$ 364.51万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-02-14 至 2011-08-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7784531
关键词：
General Clinical Research Center

项目摘要

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.

高血压是经常遇到的，当生病的新生儿接受TPN提供葡萄糖超过婴儿正常的葡萄糖周转率。最近对重症儿童和成人的研究表明，表明高血糖与死亡率增加有关。因为生病的新生儿，特别是出生体重极低的人也是高危人群，预防高血糖，减少他们的能量摄入，可能会降低他们出现不良后果的风险。完成这一目标需要详细了解与高血糖症发展有关的潜在因素（调节葡萄糖产生、糖原生成、糖原分解、葡萄糖利用;以及胰岛素分泌和胰岛素以及例如胰岛素输注和降低的葡萄糖输注速率影响降低血糖。这些问题将通过本文档中描述的协议来解决。修订的竞争性续约补助金提案。将在75个ELBW（极低）中检验以下假设低出生体重）婴儿在5年期间：1。异源生殖的速率不会因葡萄糖输注速率降低导致葡萄糖和胰岛素浓度降低， 3 mg/kg min; 2.输注胰岛素a）不会急性抑制胰岛素生成率; B）增加葡萄糖与体重成比例的利用; c）增加蛋白质合成; 3.接受标准TPN的婴儿，高血糖症主要是胰岛素分泌不足的结果。这些研究将提高我们对调节葡萄糖的产生，糖原合成和糖原分解; 高血糖和胰岛素输注影响葡萄糖和蛋白质代谢的机制。一对控制极低出生体重儿葡萄糖稳态的机制有清楚的了解婴儿将使我们能够制定循证策略，以维持健康，同时提供适当的能量摄入