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(由申请人提供)：败血症是一种危及生命的疾病，其特征是对感染产生强烈的炎症反应，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。导致高血糖的因素尚不完全清楚，但最近我们的实验室证明，以静脉输注葡萄糖的形式进行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，败血症和葡萄糖输注都是脓毒症小鼠发生代谢功能障碍和高血糖所必需的，高血糖的发生与炎症增加和死亡率增加有关。我们这项建议的目的是了解营养支持的输送途径(肠内或肠外)如何影响败血症患者代谢功能障碍的发展。危重患者接受管状喂养形式的肠内营养，尽管全肠外营养的使用有所减少，但肠外葡萄糖输注在维持液和药物载体中仍然很常见。我们假设，与肠外输注相比，脓毒症期间肠内注射葡萄糖将与改善代谢和炎症结果相关。我们将以以下目的验证这一假说：(1)我们将使用频繁采样的静脉葡萄糖耐量试验来确定营养支持途径对小鼠内毒素血症代谢功能障碍和炎症发展的影响，以及(2)我们将确定胰岛素激素胃抑制肽和胰高血糖素样肽1在改善败血症期间血糖控制方面的作用以及它们在营养支持途径方面的不同之处。总之，这些研究将为旨在改善危重患者预后的转化性研究的未来发展提供平台。这项提议将允许候选人，一名正在接受培训的内科科学家，有机会进一步发展为一名翻译科学家，并成为动物模型和人类研究之间的桥梁。这位候选人最近有临床研究的背景，通过实验室经验和与他的导师的会议，他将获得开发动物模型的经验，以回答原本仅在人体研究中难以回答的问题。此外，他将接受临床研究硕士学位培训，重点是翻译科学，这将加强他在基础科学和临床研究方面的背景。他的导师O‘Donnell博士和McVerry博士拥有广泛的资源和知识，使他能够发展成为一名转化型科学家，他将得到肺、过敏和重症监护医学部的大力支持，该部门已表现出对他作为一名独立临床医生研究员的坚定承诺。