Figure 4
Proposed physiological pathways of oxygen-18 isotopic fractionation in diabetes.
At fasting state, carbonic anhydrase (CA) loses its enzymatic activity in diabetes subjects due to formation of excess glycosylated carbonic anhydrase molecules (G-CAs) in erythrocytes. The decrease in enzymatic activity of CA is the maximum in T1D as erythrocytes are exposed to the highest level of glucose-mediated environment in T1D than T2D. When a dose containing of 75 g of normal glucose is administered (step-I), due to lack of insulin, the exogenous glucose cannot enter into muscle tissue (step-II) in T1D. Therefore, the non-insulin dependent free fatty acids (FFAs) oxidation is facilitated to produce ketone bodies during metabolism in liver (step-III).This may alter the reverse isotopic fractionation reaction to deplete the 18O-isotope in exhaled breath CO2 at post-dose state (step-IV to step-V).
