Introduction: There is a pressing need to develop a new and an effective strategy for early detection of T1D and to precisely distinguish T1D from type 2 diabetes (T2D). The aim of the present study was to find out the potential link between the erythrocytes carbonic anhydrase (CA) activity and ¹⁸O-isotopic exchange of breath CO₂ in T1D and T2D.

Methods: Fasting and post-dose breath and blood samples were collected simultaneously after ingestion of 75-gm normal glucose dissolved in 150-mL water. Blood samples were analysed to measure the CA activity. The breath samples were utilised to measure the carbon dioxide isotopes (¹²C¹⁶O¹⁶O, ¹³C¹⁶O¹⁶O and ¹²C¹⁶O¹⁸O) by a laser based high-precision carbon dioxide isotope analyzer.

Results: The CA activities are markedly altered during metabolism of T1D and T2D and this facilitates to oxygen-18 (¹⁸O) isotopic fractionations of breath CO₂. In our observations, T1D exhibited considerable depletions of ¹⁸O-isotopes of CO_2, whereas T2D manifested isotopic enrichments of ¹⁸O in breath CO₂, thus unveiling a missing link of breath¹⁸O-isotopic fractionations in T1D and T2D. The optimal diagnostic cut-off points were determined to be δ_DOB¹⁸O‰ = 2.1‰ and ΔCA = 3.15 U/min/mL for screening T1D and T2D individuals.

Conclusions: Our findings suggest the changes in erythrocytes CA activities may be the initial step of altered metabolism of T1D and T2D, and breath ¹⁸O-isotope regulated by the CA activity is a potential diagnostic biomarker that can selectively and precisely distinguish T1D from T2D and thus may open a potential unifying strategy for treating these diseases.