Oxygen-18 and carbon-13 isotopes in eCO2 and erythrocytes carbonic anhydrase activity of Finnish prediabetic population

Complex human physiological processes create the stable isotopic composition of exhaled carbon dioxide (eCO(2)), measurable with noninvasive breath tests. Recently, isotope-selective breath tests utilizing natural fluctuation in O-18/O-16 isotope ratio in eCO(2) have been proposed for screening prediabetic (PD) individuals. It has been suggested that O-18/O-16 fractionation patterns reflect shifts in the activity of carbonic anhydrase (CA), an enzyme involved in the metabolic changes in the PD state. To evaluate the applicability of the breath sampling method in Finnish PD individuals, breath delta values (BDVs, parts per thousand) of O-18/O-16 (delta O-18) were monitored for 120 min in real-time with a high-precision optical isotope ratio spectrometer, both in the fasting state and during a 2 h oral glucose tolerance test (2 h OGTT) with non-labeled glucose. In addition, the BDV of C-13/C-12 (delta C-13) was measured, and total erythrocyte CA activity was determined. delta O-18 and CA did not demonstrate any statistically significant differences between PD and non-diabetic control (NDC) participants. Instead, delta C-13 was significantly lower in PD patients in comparison to NDCs in the fasting state and at time points 90 and 120 min of the 2 h OGTT, thus indicating slightly better potential in identifying Finnish PD individuals. However, overlapping values were measured in PD participants and NDCs, and therefore, delta C-13 cannot be applied as a sole measure in screening prediabetes at an individual level. Thus, because the combination of environmental and lifestyle factors and anthropometric parameters has a greater effect on glucose metabolism and CA activity in comparison to the PD state, O-18/O-16 and C-13/C-12 fractionations or CA activity did not prove to be reliable biomarkers for impaired glucose tolerance in Finnish subjects. This study was conducted under the clinicaltrials.gov ID NCT03156478.

Automated summary

Analyzing the isotopic composition of exhaled carbon dioxide may help screen for prediabetes, but further research is needed to apply this method in Finnish individuals with prediabetes. While C-13/C-12 isotopes may assist in identifying prediabetic individuals in some cases, they are not yet reliable as a sole marker for screening prediabetes.