Targeting erythrocyte carbonic anhydrase and ¹⁸O-isotope of breath CO₂ for sorting out type 1 and type 2 diabetes

The inability to envisage the acute onset and progression of type 1 diabetes (T1D) has been a major clinical stumbling block and an important area of biomedical research over the last few decades. Therefore 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). Here we describe the precise role of the enzymatic activity of carbonic anhydrase (CA) in erythrocytes in the pathogenesis of T1D and T2D. We show that CA activities are markedly altered during metabolism of T1D and T2D and this facilitates to the oxygen-18 (¹⁸O) isotopic fractionations of breath CO₂. In our observations, T1D exhibited considerable depletions of ¹⁸O-isotopes of CO₂, whereas T2D manifested isotopic enrichments of ¹⁸O in breath CO₂, thus unveiling a missing link of breath ¹⁸O-isotopic fractionations in T1D and T2D. Our findings suggest that the alterations 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.