Non-invasive ¹³ C-glucose breath test using residual gas analyzer-mass spectrometry: a novel tool for screening individuals with pre-diabetes and type 2 diabetes

Abstract

We report, for the first time, the clinical feasibility of a novel residual gas analyzer mass spectrometry (RGA-MS) method for accurate evaluation of the (13)C-glucose breath test ((13)C-GBT) in the diagnosis of pre-diabetes (PD) and type 2 diabetes mellitus (T2D). In T2D or PD, glucose uptake is impaired and results in blunted isotope enriched (13)CO2 production in exhaled breath samples. Using the Receiver operating characteristics (ROC) curve analysis, an optimal diagnostic cut-off point of the (13)CO2/(12)CO2 isotope ratios expressed as the delta-over-baseline (DOB) value, was determined to be δDOB(13)C‰ = 28.81‰ for screening individuals with non-diabetes controls (NDC) and pre-diabetes (PD), corresponding to a sensitivity of 100% and specificity of 94.4%. We also determined another optimal diagnostic cut-off point of δDOB(13)C‰ = 19.88‰ between individuals with PD and T2D, which exhibited 100% sensitivity and 95.5% specificity. Our RGA-MS methodology for the (13)C-GBT also manifested a typical diagnostic positive and negative predictive value of 96% and 100%, respectively. The diagnostic accuracy, precision and validity of the results were also confirmed by high-resolution optical cavity enhanced integrated cavity output spectroscopy (ICOS) measurements. The δDOB(13)C‰ values measured with RGA-MS method, correlated favourably (R(2) = 0.979) with those determined by the laser based ICOS method. Moreover, we observed that the effects of endogenous CO2 production related to basal metabolic rates in individuals were statistically insignificant (p = 0.37 and 0.73) on the diagnostic accuracy. Our findings suggest that the RGA-MS is a valid and sufficiently robust method for the (13)C-GBT which may serve as an alternative non-invasive point-of-care diagnostic tool for routine clinical practices as well as for large-scale diabetes screening purposes in real-time.

Halloysite Nanotubes Capturing Isotope Selective Atmospheric CO2

“…In brief, the ICOS spectrometer is comprised of a continuous wave diode laser operating at ~2.05 μm and a high-finesse optical cavity. The two high reflectivity mirrors (R ~ 99.98%) at the two ends of the measurement cell (~59 cm) allow the laser light to move back and forth provide an effective optical path-length of ~3 km44. The laser frequency was tuned to scan over 20 GHz to record the absorption spectra of 12 C 18 O 16 O (4874.178 cm −1 ), 12 C 16 O 16 O (4874.448 cm −1 ) and 13 C 16 O 16 O (4874.086 cm −1 ) in the (2,0 0 ,1)←(0,0 0 ,0) vibrational combination band of the CO 2 molecule.…”

Oxygen-18 isotope of breath CO2 linking to erythrocytes carbonic anhydrase activity: a biomarker for pre-diabetes and type 2 diabetes

“…Members from families with previous history of diabetes were also excluded from the study. Subjects were classified into three groups of type 2 diabetes (T2D), pre-diabetes (PD) and non-diabetic controls (NDC) according to the current criteria outlined by the American Diabetes Association 19 . Individuals with T2D were determined with glycosylated hemoglobin (HbA1c %) ≥ 6.5 and 2 hr glucose ≥ 200 mg/dL during an oral glucose tolerance test (OGTT), whereas PD was determined with 5.7 ≤ HbA1c (%) < 6.5 and 140 mg/dL ≤ 2 hr OGTT glucose < 200 mg/dL.…”

Failure of hyperglycemia and hyperinsulinemia to compensate for impaired metabolic response to an oral glucose load

“…We and others have previously found differences by obesity or insulin resistance status in the breath response following 13 C-labeled glucose (22, 24, 29, 30). These observations, along with those currently presented, are in contrast to a recent study using an analogous method, ingesting 2 H-labeled glucose and measuring appearance of labeled 2 H 2 O in total body water (21).…”