Effect of Route of Nutritional Support on Metabolic and Inflammatory Outcomes in Sepsis

营养支持途径对脓毒症代谢和炎症结果的影响

• 批准号: 9150293
• 负责人: Faraaz Ali Shah
• 金额: $ 0.74万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2016-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9150293
• 关键词: Affect; Animal Model; Attenuated; Basic Science; Cannulas; Cessation of life; Clinical Research; Clinical Trials; Critical Care; Critical Illness; Dedications; Development; Diabetes Mellitus; Dietary Intervention; Endotoxemia; Enteral; Enteral Feeding; Enteral Nutrition; Functional disorder; Future; Gastric Inhibitory Polypeptide; Glucose; Human; Hyperglycemia; Hypersensitivity; Implant; Infection; Inflammation; Inflammatory; Inflammatory Response; Infusion procedures; Interleukin-1 beta; Interleukin-6; Investigation; Kinetics; Knowledge; Laboratories; Life; Ligation; Lipopolysaccharides; Liquid substance; Lung; Maintenance; Master' s Degree; Mediating; Medicine; Mentors; Metabolic; Metabolism; Morbidity - disease rate; Mus; Nutrition Therapy; Nutritional Support; Organ; Outcome; Parenteral Nutrition; Pathway interactions; Patients; Pharmaceutical Preparations; Physicians; Play; Population Heterogeneity; Process; Puncture procedure; Recovery; Relative Risks; Research; Research Personnel; Resources; Risk; Role; Route; Sampling; Scientist; Sepsis; Signal Transduction; Stomach; Supplementation; TNF gene; Testing; Time; Total Parenteral Nutrition; Training; Translational Research; Work; analog; base; career; cytokine; experience; glucagon-like peptide; glucagon-like peptide 1; glucose metabolism; glycemic control; improved; improved outcome; in vivo; incretin hormone; insulin secretion; insulin sensitivity; intravenous glucose tolerance test; laboratory experience; meetings; mortality; mouse model; nutrition; nutritional supplementation; parenteral administration; prevent; public health relevance; septic; targeted treatment; training opportunity; translational study

 DESCRIPTION (provided by applicant): Project Summary Sepsis is a life threatening illness characterized by an overwhelming inflammatory response to infection, and the development of hyperglycemia during sepsis is associated with increased organ dysfunction and mortality. The factors contributing to the development of hyperglycemia are not completely understood but recently our laboratory demonstrated that nutritional support, in the form of parenteral infusions of dextrose, can have important effects on metabolic outcomes in sepsis. We found that both septic insult and dextrose infusions were necessary for the development of metabolic dysfunction and hyperglycemia in mouse models of sepsis and that development of hyperglycemia was associated with increased inflammation and increased mortality. Our objective for this proposal is to understand how the route of delivery of nutritional support (enteral or parenteral) influences the development of metabolic dysfunction in sepsis. Critically ill patients receive enteral nutrition in the form of tube feeds, and although the use of total parenteral nutrition has declined, parenteral dextrose infusions remain common in maintenance fluids and as medication carriers. We hypothesize that enteral administration of dextrose during sepsis will be associated with improved metabolic and inflammatory outcomes compared to parenteral infusion. We will test this hypothesis with the following aims: (1) We will determine the effect of route of nutritional support on development of metabolic dysfunction and inflammation in murine endotoxemia with the use of the frequently sampled intravenous glucose tolerance test, and (2) We will determine the roles of the incretin hormones gastric inhibitory peptide and glucagon like peptide 1 in improving glycemic control during sepsis and how they differ based on route of nutritional support. Together these studies will provide the platform for future development of translational investigations targeting improvement in outcomes of critically ill patients. This proposal will allow the candidate, a physician scientist in-training, the opportunity to develop further as a translational scientist and bridge between animal models and human studies. The candidate has a recent background in clinical research and through lab experience and meetings with his mentors will be gaining experience in developing animal models to answer questions that are otherwise difficult to answer solely in human studies. Additionally, he will undertake Master's degree training in Clinical Research with a focus in Translational Science which will strengthen his background in both basic science and clinical research. His mentors, Drs. O'Donnell and McVerry have extensive resources and knowledge to allow him to develop as a translational scientist and he will be well-supported by the Division of Pulmonary, Allergy, and Critical Care Medicine, which has demonstrated strong commitment to his development as an independent clinician investigator.

 描述（由适用提供）：项目摘要败血症是一种威胁生命的疾病，其特征是对感染的压倒性炎症反应，并且败血症期间高血糖的发展与器官功能障碍和死亡率的增加有关。尚未完全了解导致高血糖发展的因素，但最近我们的实验室表明，以葡萄糖的亲本输注形式的营养支持可以对败血症的代谢结果产生重要影响。我们发现，败血症小鼠模型中的代谢功能障碍和高血糖的发展和高血糖的发展与感染和死亡率的增加有关，败血症损伤和葡萄糖输注都是必要的。我们对该提案的目标是了解营养支持（肠或肠胃外）的提供途径如何影响败血症代谢功能障碍的发展。重要的是，IR患者以管子饲料的形式接受肠内营养，尽管使用总父母营养的使用已经下降，但父母葡萄糖输注在维护烟道和药物载体中仍然很常见。我们假设与父母输注相比，败血症期间葡萄糖的肠内给药与代谢和炎症结果的改善有关。我们将以以下目的检验这一假设：（1）我们将通过使用经常采样的静脉内葡萄糖耐受性测试来确定营养支持对鼠内毒素的代谢功能障碍和注射鼠内毒性的影响的影响，并且（2）我们将确定固定蛋白抑制性蛋白质和粘膜固定剂的作用，例如，我们将确定固定蛋白甲抑制剂的作用。根据营养支持途径，它们如何与众不同。这些研究将共同​​为未来开发转化调查的发展提供一个平台，以改善重症患者的结果。该建议将使候选人是一名物理科学家训练的机会，是动物模型与人类研究之间的翻译科学家和桥梁进一步发展的机会。候选人在临床研究方面具有最新的背景，并通过实验室经验和与他的导师会议的会议将获得开发动物模型的经验，以回答这些问题，而这些问题原本很难仅在人类研究中回答。此外，他将接受临床研究的硕士学位培训，重点是转化科学，这将增强他在基础科学和临床研究中的背景。他的导师博士。 O'Donnell和McVerry拥有丰富的资源和知识，使他能够发展为翻译科学家，他将受到肺部，过敏和重症监护医学的良好支持，这表明他作为一名独立的临床研究者表现出了坚定的承诺。