Intra-Individual Variability of CO2 Breath Isotope Enrichment Compared to Blood Glucose in the Oral Glucose Tolerance Test

Abstract

Glucose tolerance can be assessed noninvasively using (13)C-labeled glucose added to a standard oral glucose load, by measuring isotope-enriched CO(2) in exhaled air. In addition to the clear advantage of the noninvasive measurements, this approach may be of value in overcoming the high variability in blood glucose determination. We compared within-individual variability of breath CO(2) isotope enrichment with that for blood glucose in a 75-g oral glucose tolerance test (OGTT) by adding 150 mg of d-[(13)C]glucose ((13)C 99%) to a standard 75-g glucose load. Measurements of whole blood glucose (by glucose oxidase) and breath isotope enrichment (by isotope ratio mass spectrometry) were made every 30 min for 3 h. Subjects underwent three repeat tests over a 3-week period. Values for variability of breath isotope enrichment at 3 h (∂‰180) and of area under the curve for enrichment to 180 min (AUC180) were compared with variability of the 2-h OGTT blood glucose. Breath test-derived measures exhibited lower within-subject variability than the 2-h OGTT glucose. The coefficient of variation for ∂‰180 was 7.4 ± 3.9% (mean ± SD), for AUC180 was 9.4 ± 6.3%, and for 2-h OGTT blood glucose was 13 ± 7.1% (P = 0.005 comparing ∂‰180 versus 2-h blood glucose; P = 0.061 comparing AUC180 versus 2-h blood glucose; P = 0.03 comparing ∂‰180 versus AUC180). Breath test-derived measurements of glucose handling had lower within-subject variability versus the standard 2-h blood glucose reading used in clinical practice. These findings support further development of this noninvasive method for evaluating glucose tolerance.