GLUCOSE KINETICS IN SUBJECTS WITH MELAS SYNDROME

黄斑综合症受试者的葡萄糖动力学

• 批准号: 8356751
• 负责人: WILLIAM James CRAIGEN
• 金额: $ 1.15万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356751
• 关键词: Age of Onset; Clinical Research; Defect; Dementia; Diabetes Mellitus; Epilepsy; Exercise; Funding; Gluconeogenesis; Glucose; Grant; Individual; Infusion Technique; Inherited; Insulin; Isotopes; Kinetics; Lactic Acidosis; Measures; Metabolism; Mitochondrial Diseases; Mitochondrial Encephalomyopathies; National Center for Research Resources; Pathogenesis; Principal Investigator; Red Fiber; Research; Research Infrastructure; Resources; Source; Stroke; Symptoms; Syndrome; United States National Institutes of Health; cost; design; glucose production; glycogenolysis; insight; insulin sensitivity; outcome forecast; oxidation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The mitochondrial encephalomyopathy, lactic acidosis, with stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. It has a broad spectrum of symptoms and variable age of onset. Common manifestations include exercise intolerance, stroke-like episodes, epilepsy, ragged red fibers, lactic acidosis, and dementia. It has been estimated that one third of individuals with MELAS syndrome develop diabetes mellitus (DM). The pathogenesis of DM in MELAS syndrome is not clear and there are no clinical studies evaluating glucose/insulin metabolism in individuals with MELAS syndrome. We hypothesize that DM develops in individuals with MELAS syndrome due to multiple defects in glucose/insulin metabolism and that individuals with MELAS syndromes who do not yet have DM have altered glucose/insulin metabolism. To investigate these hypotheses, we designed a clinical study to assess glucose/insulin metabolism in individuals with MELAS syndrome who do or do not have DM, and in healthy control individuals. Glucose/insulin metabolism will be assessed by glucose isotope infusion technique and measuring the rates of endogenous glucose production, gluconeogenesis, glycogenolysis, glucose oxidation, and glucose clearance; insulin levels; and insulin sensitivity. Understanding the pathophysiological mechanism of DM in MELAS syndrome can influence the management and prognosis of DM in subjects with MELAS syndrome, and may provide more insight of the pathogenesis of DM in mitochondrial diseases in general.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 线粒体脑肌病，乳酸酸中毒，中风样发作（MELAS）综合征是最常见的母系遗传性线粒体疾病之一。它具有广泛的症状和不同的发病年龄。常见的表现包括运动不耐受、中风样发作、癫痫、粗糙的红纤维、乳酸酸中毒和痴呆。据估计，三分之一的MELAS综合征患者会发展为糖尿病（DM）。MELAS综合征中DM的发病机制尚不清楚，也没有临床研究评估MELAS综合征患者的葡萄糖/胰岛素代谢。我们假设，糖尿病的发展与MELAS综合征的个人，由于多种缺陷的葡萄糖/胰岛素代谢和MELAS综合征的个人谁还没有DM改变葡萄糖/胰岛素代谢。为了研究这些假设，我们设计了一项临床研究，以评估MELAS综合征患者（有或无DM）和健康对照者的葡萄糖/胰岛素代谢。将通过葡萄糖同位素输注技术并测量内源性葡萄糖生成、糖原生成、糖原分解、葡萄糖氧化和葡萄糖清除率;胰岛素水平;和胰岛素敏感性来评估葡萄糖/胰岛素代谢。 了解MELAS综合征中DM的病理生理机制可以影响MELAS综合征受试者中DM的管理和预后，并且可以提供对一般线粒体疾病中DM发病机制的更多了解。