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

Anna Kårlund,Marjukka Kolehmainen,Vili M Kostamo,Timo A Lakka,Tarja Kokkola,Teemu Kääriäinen,Jussi Pihlajamäki,Albert Manninen

doi:10.1088/1752-7163/abd28d

Abstract

Complex human physiological processes create the stable isotopic composition of exhaled carbon dioxide (eCO2), measurable with noninvasive breath tests. Recently, isotope-selective breath tests utilizing natural fluctuation in 18O/16O isotope ratio in eCO2 have been proposed for screening prediabetic (PD) individuals. It has been suggested that 18O/16O 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, ‰) of 18O/16O (δ 18O) 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 13C/12C (δ 13C) was measured, and total erythrocyte CA activity was determined. δ 18O and CA did not demonstrate any statistically significant differences between PD and non-diabetic control (NDC) participants. Instead, δ 13C 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, δ 13C 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, 18O/16O and 13C/12C 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.

Highlights

The stable isotopic composition of exhaled carbon dioxide displays characteristics of the physical process of origin of the molecule
Anthropometrics, fasting blood glucose, fasting serum insulin, HbA1c, isotopic fractionations and carbonic anhydrase (CA) activity in the study groups are presented in table 1
Based on the results of this study, measuring δ13C during 2 h OGTT could support the identification Finnish PD individuals, as characteristic δ13C in PD and non-diabetic control (NDC) subjects seemed to indicate the differences in insulin response and glucose metabolism between the study groups

Summary

Introduction

The stable isotopic composition of exhaled carbon dioxide (eCO2) displays characteristics of the physical process of origin of the molecule. Isotopic recovery via noninvasive breath tests can provide signatures, for example, for many complex human physiological phenomena, such as diseases, medical conditions, energy consumption, and changes in various body functions [1, 2]. The stable isotope breath tests are commonly based on ingestion of a carbon-13 (13C)-labeled substrate, which is converted into 13CO2 via metabolism and is detected as a change in the baseline 13C/12C ratio in eCO2. The most well-known example among isotope-selective breath tests is the 13C-labeled urea breath test (13C-UBT), used to identify Helicobacter pylori infection. Along with labeled 13C, the measurement of oxygen-16 (16O) and oxygen-18 (18O) isotopes in exhaled breath can be exploited in noninvasive studies and diagnostic approaches [7,8,9]

Methods

Results

Discussion

Conclusion