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

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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.