Intra-individual variability of C[O.sub.2] breath isotope enrichment compared to blood glucose in the oral glucose tolerance test

Background: Glucose tolerance can be assessed noninvasively using [sup.13]C-labeled glucose added to a standard oral glucose load, by measuring isotope-enriched C[O.sub.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. Methods: We compared within-individual variability of breath C[O.sub.2] isotope enrichment with that for blood glucose in a 75-g oral glucose tolerance test (OGTT) by adding 150 mg of D-[[sup.13]C]glucose ([sup.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. Results: 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). Conclusions: 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.