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Non-invasive investigation of metabolic processes in pediatric diabetes mellitus type 1 patients by means of volatile organic compounds in the breath

通过呼吸中的挥发性有机化合物对儿童 1 型糖尿病患者的代谢过程进行无创研究

基本信息

批准号：
314725332
负责人：
Dr. Phillip Trefz
金额：
--
依托单位：
Kinder- und Jugendklinik
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/314725332?language=en
关键词：
Non invasive investigation metabolic processes

项目摘要

Pediatric diabetes mellitus type 1 can be seen as prototype of clinically relevant metabolic disorders. The non-invasive analysis of human breath offers great potential for fundamental and repeated investigations in pediatric patients with diabetes. The application of non-invasive methods would be highly desirable in the field of pediatrics, as repeated examinations can be hindered by the aversion of children against invasive procedures. Aim of the project is the non-invasive monitoring of metabolic processes by means of volatile organic biomarkers that are identified and validated in comparison to healthy children and teenagers. Investigations of VOC profiles, except for acetone and isoprene, are not available in pediatric patients yet. Hence, the combination of innovative VOC analysis and (established) clinical monitoring has the potential to provide fundamental and complementary results on the progress of DM 1 in children. Besides the identification of potential non-invasive markers, the variability of marker profiles over time will also be investigated, especially regarding metabolic processes that are subject to great variations. Thus the relation of potential biomarkers to glycemic variability will be analyzed by means of high resolution mass spectrometry (PTR-ToF-MS) after the identification of potential biomarkers via laboratory based techniques (NTME-GC-MS). The results will build a scientific basis for the development of non-invasive methods for monitoring and therapy control of DM 1 in children. The following issues will be addressed in a cross-sectional study in more than 100 volunteers and a study that combines continuous glucose monitoring and breath analysis:Attention is particularly dedicated to volatile markers that are associated with glucose- and lipid metabolism as well as oxidative stress. The scientific reasoning behind this selection are the importance of hypo- and hyperglycemia, ketoacidosis conditions and cellular damage caused by reactive oxygenated species during the course of disease of DM 1. The following issues will be adressed in detail in a cross-sectional study in more than 100 volunteers and a study that combines continuous glucose monitoring and breath analysis:Identification and characterization of the volatile metabolome in pediatric diabetes mellitus type 1 patients.Definition of differences in VOC profiles between DM 1 patients and healthy controls regarding concentration or variability.Determination of sensitivity and specificity of volatile breath markers with respect to the recognition of hyper- and hypoglycemia as well ketoacidosis conditions in comparison to conventional diagnostic methods (CGM, serum markers etc.).Apart from the scientific gain of knowledge regarding pathophysiology and course of disease, an improvement of patient outcome by means of a simplified, non-invasive therapy control can be expected in perspective.

儿童1型糖尿病可被视为临床相关代谢紊乱的原型。人类呼吸的非侵入性分析为糖尿病儿科患者的基础和重复研究提供了巨大的潜力。非侵入性方法的应用在儿科领域中是非常期望的，因为重复检查可能会受到儿童对侵入性程序的厌恶的阻碍。该项目的目的是通过挥发性有机生物标志物对代谢过程进行非侵入性监测，并与健康儿童和青少年进行比较。除丙酮和异戊二烯外，尚未在儿科患者中进行VOC特征研究。因此，创新的VOC分析和（已建立的）临床监测相结合，有可能为儿童1型糖尿病的进展提供基本和补充的结果。除了鉴定潜在的非侵入性标志物外，还将研究标志物谱随时间的变化，特别是关于易发生巨大变化的代谢过程。因此，在通过基于实验室的技术（NTME-GC-MS）鉴定潜在生物标志物后，将通过高分辨率质谱法（PTR-ToF-MS）分析潜在生物标志物与血糖变异性的关系。本研究结果将为儿童1型糖尿病的无创监测和治疗控制提供科学依据。以下问题将在100多名志愿者的横断面研究和一项结合连续葡萄糖监测和呼吸分析的研究中得到解决：特别关注与葡萄糖和脂质代谢以及氧化应激相关的挥发性标志物。这种选择背后的科学推理是DM 1疾病过程中低血糖和高血糖、酮症酸中毒状况和由活性氧合物质引起的细胞损伤的重要性。以下问题将在100多名志愿者的横断面研究和一项结合连续血糖监测和呼吸分析的研究中详细讨论：儿童1型糖尿病患者挥发性代谢物组的鉴定和表征。确定1型糖尿病患者和健康对照组之间VOC浓度或变异性的差异。确定挥发性呼吸标记物识别高浓度和低浓度的敏感性和特异性。和低血糖症以及酮症酸中毒状况。除了获得有关病理生理学和病程的科学知识外，还可以预期通过简化的非侵入性治疗控制来改善患者结局。