Glucosylation of human haemoglobin A. Dynamic variation in HbA1c described by a biokinetic model

The reaction kinetics for the reversible condensation of D-glucose and haemoglobin A through a labile haemoglobin A-aldimine adduct to HbA1c have been investigated using a biokinetic model. The specific rate constants obtained from in vitro experiments were included in the model which also took into account the removal of HbA1c by decay of erythrocytes. Using a sinusoidal variation in blood glucose a phase delay of about 2 hours was observed between the maximum blood glucose concentration and the maximum aldimine concentration. The mean haemoglobin A-aldimine concentration was independent of both the amplitude and frequency of the blood glucose oscillations and reached equilibrium concentration within 24 hours. The steady state relation between mean blood glucose and HbA1c was similar to the corresponding relation based on an irreversible formation of HbA1c. However, contrary to the irreversible model the steady state HbA1c concentration with the reversible model was reached 3 to 4 weeks after a change in blood glucose level. This finding is in agreement with clinical experience and indicates that in assessing continuous glycaemic control in diabetic patients haemoglobin A1c should be measured approximately every 3 to 4 weeks.