title: Noninvasive measurement of plasma glucose from exhaled breath in healthy and type 1 diabetic subjects.
abstract: Effective management of diabetes mellitus, affecting tens of millions of patients, requires frequent assessment of plasma glucose. Patient compliance for sufficient testing is often reduced by the unpleasantness of current methodologies, which require blood samples and often cause pain and skin callusing. We propose that the analysis of volatile organic compounds (VOCs) in exhaled breath can be used as a novel, alternative, noninvasive means to monitor glycemia in these patients. Seventeen healthy (9 females and 8 males, 28.0 ± 1.0 yr) and eight type 1 diabetic (T1DM) volunteers (5 females and 3 males, 25.8 ± 1.7 yr) were enrolled in a 240-min triphasic intravenous dextrose infusion protocol (baseline, hyperglycemia, euglycemia-hyperinsulinemia). In T1DM patients, insulin was also administered (using differing protocols on 2 repeated visits to separate the effects of insulinemia on breath composition). Exhaled breath and room air samples were collected at 12 time points, and concentrations of ~100 VOCs were determined by gas chromatography and matched with direct plasma glucose measurements. Standard least squares regression was used on several subsets of exhaled gases to generate multilinear models to predict plasma glucose for each subject. Plasma glucose estimates based on two groups of four gases each (cluster A: acetone, methyl nitrate, ethanol, and ethyl benzene; cluster B: 2-pentyl nitrate, propane, methanol, and acetone) displayed very strong correlations with glucose concentrations (0.883 and 0.869 for clusters A and B, respectively) across nearly 300 measurements. Our study demonstrates the feasibility to accurately predict glycemia through exhaled breath analysis over a broad range of clinically relevant concentrations in both healthy and T1DM subjects.
authors.affiliation: Department of Pharmacology, University of California Irvine, Irvine, CA 92697, USA. tminh@uci.edu
authors.forename: Timothy D C
authors.initials: TD
authors.lastname: Minh
authors.forename: Stacy R
authors.initials: SR
authors.lastname: Oliver
authors.forename: Jerry
authors.initials: J
authors.lastname: Ngo
authors.forename: Rebecca
authors.initials: R
authors.lastname: Flores
authors.forename: Jason
authors.initials: J
authors.lastname: Midyett
authors.forename: Simone
authors.initials: S
authors.lastname: Meinardi
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Carlson
authors.forename: F Sherwood
authors.initials: FS
authors.lastname: Rowland
authors.forename: Donald R
authors.initials: DR
authors.lastname: Blake
authors.forename: Pietro R
authors.initials: PR
authors.lastname: Galassetti
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D001944:Breath Tests / Q000379:methods*; D002849:Chromatography, Gas; D016000:Cluster Analysis; D003627:Data Interpretation, Statistical; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D005740:Gases / Q000032:analysis; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D016014:Linear Models; D008297:Male; D009566:Nitrates / Q000032:analysis; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D055549:Volatile Organic Compounds / Q000032:analysis
chemical_list: D001786:Blood Glucose; D005740:Gases; D007328:Insulin; D009566:Nitrates; D055549:Volatile Organic Compounds; D005947:Glucose; C421036:methyl nitrate