OBJECTIVE: Diagnosis of pre-diabetes and early-stage diabetes occurs primarily by means of an oral glucose tolerance test (OGTT), which requires invasive blood sampling. The aim of this study was to determine whether differences exist in breath (13)CO(2) excretion during a (13)C-labeled OGTT between individuals with normal glucose tolerance (NGT) and individuals with pre-diabetes and early-stage diabetes (PDED) and whether these differences correlated with blood glucose kinetics. RESEARCH DESIGN AND METHODS: Blood and breath samples were collected at baseline and every 30 min for a 10-h period after ingestion of 75 g glucose isotopically labeled with 150 mg [U-(13)C(6)]D-glucose. RESULTS: Age (56 +/- 5 vs. 47 +/- 3 years) and BMI (31 +/- 2 vs. 31 +/- 2 kg/m(2)) were not different between individuals with NGT (n = 10) and PDED (n = 7), respectively. Blood glucose concentrations were significantly higher in those with PDED compared with those with NGT from baseline to 4.5 h after glucose ingestion (P <or= 0.05). Glucose-derived breath (13)CO(2) was significantly lower in individuals with PDED compared with those with NGT from 1 to 3.5 h after glucose (P <or= 0.05). Peak breath (13)CO(2) abundance occurred at 4.5 and 3.5 h in individuals with PDED and NGT, respectively (36.87 +/- 3.15 vs. 41.36 +/- 1.56 per thousand delta over baseline). CONCLUSIONS: These results suggest that this novel breath test method may assist in recognition of pre-diabetes or early-stage diabetes in at-risk persons without the need for invasive blood sampling, thus making it an attractive option for large-scale testing of at-risk populations, such as children.