Volatile organic compounds in breath are produced during hypoglycemia (hypo VOCs) are detectable by canines and by GC/MS analysis of human breath. However, it is not known whether hypo VOCs fall or recover at the same time or before or after plasma glucose (PG) levels. Breath samples were collected from 11 volunteers with type 1 diabetes during an insulin clamp study at different Checkpoints, including: Initial (fasting; median 150 mg/dL (range 107-333), Euglycemia (90 and 80 mg/dL), Hypoglycemia (Hypo; 70, 60, 50 mg/dL) and after PG returned to 90 mg/dL (Recovery; 35 (23-62 min from last Hypo sampling)). In total, 94 breath samples were analyzed by GC/MS. We compared VOC levels between Initial and Hypo Checkpoints using univariate and multivariate tests to identify hypo VOCs. Next, we analyzed the data from the Intermediate and Recovery Checkpoints. Samples collected at Euglycemia (90, 80 mg/dL) and Recovery (90 mg/dL) Checkpoints demonstrated VOC concentrations similar to those seen at Hypo Checkpoints. Fold change analysis for twelve exemplar hypo VOCs are shown in Figure 1.

In summary, breath contains VOCs that may predict hypoglycemia with falling PG well before hypoglycemia is achieved, and these VOCs may recover more slowly than plasma glucose after a hypoglycemic event. Tests for detecting hypo VOCs may provide clinically useful tools to aid in control of diabetes.

A.P. Siegel: None. A. Daneshkhah: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. M. Agarwal: None.


National Natural Science Foundation of China

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