Exhaled Methyl Nitrate As a Noninvasive Marker of Hyperglycemia in Type 1 Diabetes

Recent technical advances allow detection of several hundred volatile organic compounds (VOCs) in human exhaled air, many of which reflect unidentified endogenous pathways. Our group has previously estimated plasma glucose levels in healthy adults during a standard oral glucose tolerance test via exhaled VOC analysis. As a result of the metabolic characteristics of hyperglycemia in the diabetic (low insulin and increased free fatty acids and ketones), we hypothesized that different exhaled VOC profiles may be present in children with type 1 diabetes mellitus (T1DM) during spontaneous hyperglycemia. Exhaled methyl nitrate strongly correlated specifically with the acute, spontaneous hyperglycemia of T1DM children. Eighteen experiments were conducted among 10 T1DM children. Plasma glucose and exhaled gases were monitored during either constant euglycemia (n = 5) or initial hyperglycemia with gradual correction (n = 13); all subjects received i.v. insulin and glucose as needed. Gas analysis was performed on 1.9-liter breath samples via gas chromatography using electron capture, flame ionization, and mass selective detection. Among the approximately 100 measured exhaled gases, the kinetic profile of exhaled methyl nitrate, commonly present in room air in the range of 5-10 parts per trillion, was most strongly statistically correlated with that of plasma glucose (P = 0.003-0.001). Indeed, the kinetic profiles of the two variables paralleled each other in 16 of 18 experiments, including repeat subjects who at different times displayed either euglycemia or hyperglycemia.