GLUCOSE KINETICS IN SUBJECTS WITH MELAS SYNDROME

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 线粒体脑肌病，乳酸中毒，伴卒中样发作(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、粗糙的红色纤维、乳酸酸中毒和痴呆症。据估计，三分之一的MELAS综合征患者会患上糖尿病(DM)。糖尿病在MELAS综合征中的发病机制尚不清楚，目前尚无临床研究评估MELAS综合征患者的糖/胰岛素代谢。我们假设，患有MELAS综合征的人由于葡萄糖/胰岛素代谢的多种缺陷而发生DM，而尚未患有DM的MELAS综合征患者的葡萄糖/胰岛素代谢发生了改变。为了研究这些假说，我们设计了一项临床研究，以评估患有或不患有糖尿病的MELAS综合征患者以及健康对照组的葡萄糖/胰岛素代谢。葡萄糖/胰岛素代谢将通过葡萄糖同位素输注技术和测量内源性葡萄糖产生、糖异生、糖原分解、葡萄糖氧化和葡萄糖清除速率、胰岛素水平和胰岛素敏感性来评估。了解MELAS综合征中DM的病理生理机制可以影响MELAS综合征患者对DM的治疗和预后，并有助于从总体上更深入地了解DM的线粒体疾病的发病机制。

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.