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

儿童1型糖尿病可视为临床相关代谢紊乱的原型。对人类呼吸的非侵入性分析为儿科糖尿病患者的基础和重复研究提供了巨大的潜力。在儿科领域，非侵入性方法的应用将是非常可取的，因为重复检查可能会因为儿童对侵入性程序的厌恶而受到阻碍。该项目的目的是通过挥发性有机生物标记物对代谢过程进行非侵入性监测，并与健康的儿童和青少年进行比较。在儿科患者中，除了丙酮和异戊二烯外，尚不能对VOC谱进行调查。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DM 1的进展提供基本和补充的结果。除了识别潜在的非侵入性标记物外，还将研究标记物谱随时间的变异性，特别是关于容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)确定潜在生物标志物之后，将利用高分辨率质谱仪(PTR-ToF-MS)来分析潜在生物标志物与血糖变异性的关系。这一结果将为发展非侵入性监测和儿童DM-1治疗控制方法奠定科学基础。在一项对100多名志愿者进行的横断面研究中，以及一项将持续血糖监测和呼吸分析相结合的研究中，将解决以下问题：特别关注与葡萄糖、脂肪代谢以及氧化应激相关的挥发性标志物。这一选择背后的科学依据是低血糖和高血糖、酮症酸中毒情况以及在DM 1病程中由活性氧合物质引起的细胞损伤的重要性。在一项对100多名志愿者进行的横断面研究和一项将连续血糖监测和呼吸分析相结合的研究中，将详细讨论以下问题：儿童1型糖尿病患者挥发性代谢物的鉴定和特征。DM 1患者和健康对照组VOC谱在浓度或变异性方面的差异。挥发性呼吸标志物在识别高血糖和低血糖以及酮症酸中毒条件方面的敏感性和特异性的测定与传统诊断方法(CGM、CGM)的比较除了获得有关病理生理学和病程的科学知识外，通过一种简化的、非侵入性的治疗控制手段来改善患者的预后是可以预见的。

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.