Indole as a new tentative marker in exhaled breath for non-invasive blood glucose monitoring of diabetic subjects

Abstract

Blood glucose monitoring (BGM) is the most important part of diabetes management. In classical BGM, glucose measurement by test strips involves invasive finger pricking. We present results of a clinical study that focused on a non-invasive approach based on volatile organic compounds (VOCs) in exhaled breath. Main objective was the discovery of markers for prediction of blood glucose levels (BGLs) in diabetic patients. Exhaled breath was measured repeatedly in 60 diabetic patients (30 type 1, 30 type 2) in fasting state and after a standardized meal. Proton transfer reaction time of flight mass spectrometry was used to sample breath every 15 min for a total of 6 h. BGLs were tested in parallel via BGM test strips. VOC signals were plotted against glucose trends for each subject to identify correlations. Exhaled indole (a bacterial metabolite of tryptophan) showed significant mean correlation to BGL (with negative trend) and significant individual correlation in 36 patients. The type of diabetes did not affect this result. Additional experiments of one healthy male subject by ingestion of lactulose and 13C-labeled glucose (n = 3) revealed that exhaled indole does not directly originate from food digestion by intestinal microbiota. As indole has been linked to human glucose metabolism, it might be a tentative marker in breath for non-invasive BGM. Clinical studies with greater diversity are required for confirmation of such results and further investigation of metabolic pathways.