Novel noninvasive breath test method for screening individuals at risk for diabetes

Abstract

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.

Figure 1

Study time line. Subjects followed a 3-day standardized low-carbohydrate diet composed of 15% carbohydrate, 25% protein, and 60% fat. Individual dietary requirements were determined by a registered dietitian and calculated using the Harris Benedict equation. On the fourth day, after an overnight fast, a 10-h stable isotopically labeled OGTT was performed, and blood and breath samples were collected every 30 min.

Figure 2

Blood glucose and plasma insulin concentrations in individuals with NGT and PDED during the 10-h OGTT. A: Blood glucose was different between individuals with NGT and PDED over time as determined by mixed-model repeated measures (P < 0.05). *Different between individuals with NGT and PDED (t test, P < 0.05). B: Plasma insulin was different between individuals with NGT and PDED over time as determined by mixed-model repeated measures (P < 0.05). *Different between individuals with NGT and PDED (t test, P < 0.05).

Figure 3

Breath ¹³CO₂ abundance and areas under the curve for individuals with NGT and PDED during the 10-h OGTT. A: Breath ¹³CO₂ abundance was different between individuals with NGT and PDED over time as determined by mixed-model repeated measures (P < 0.05). *Significant difference between individuals with NGT and PDED (t test, P < 0.05). B: AUCs were different between individuals with NGT and PDED when measured from 0 to 4 h but not when measured from 0 to 10 h. *Significant difference between individuals with NGT and PDED (t test, P < 0.05).