Abstract

Detection of hypoglycemia is important to reduce risk and optimize glucose in T1D. Noninvasive glucose detection methods have not been fully explored. Exhaled breath isoprene, a component of sterol metabolism, has been associated with hypoglycemia in controlled studies in a limited population in the laboratory setting. Home-monitoring of breath isoprene levels may permit noninvasive hypoglycemia detection. We conducted an exploratory study measuring exhaled volatile organic compounds (VOCs) in breath samples collected during hypoglycemia (CBG <70 mg/dL) compared to euglycemia (CBG 70-180 mg/dL) under free-living conditions in 10 subjects age 7-74 with T1D. Breath samples were collected using designated breath capture bags and processed 1-4 weeks later by proton-transfer-reaction time-of-flight (PTR TOF) mass spectrometry. Over 100 VOCs were identified in 52 breath samples (25 hypoglycemia, 27 euglycemia). During hypoglycemia, isoprene increased 37% (p<0.05) and its oxidation products methyl vinyl ketone (MVK) and methacrolein (MACR) decreased 59% (p<0.05). However, predictive modelling using metabolite concentration as the input could not reliably predict whether the breath sample was collected during hypoglycemia or euglycemia. All other measured VOCs were not statistically different. This is the first free-living study to evaluate exhaled VOCs in patients with T1D. We successfully replicated findings of a prior study done in a controlled laboratory setting suggesting isoprene concentration in human breath increases during hypoglycemia. We further describe decreased MVK and MACR during hypoglycemia and home breath capture may be feasible for diagnostics in medical conditions. In addition, the physiology of glucose changes on sterol metabolism is worthy of further study. Finally, identification of an exhaled marker of glucose levels hints at a possible mechanism of detection by so-called diabetes alert dogs. Disclosure E.A. Los: Advisory Panel; Self; Medtronic. W.L. Stone: None. G. Ford: None. Funding East Tennessee State University (18-025M)

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