Synthesis of glycosylated haemoglobin in vivo

Summary The synthesis of glycosylated haemoglobins in vivo was measured during 24 h of controlled hyperglycaemia in seven insulin dependent diabetics. The mean blood glucose concentration was 22 mmol/l, while electrolytes and other metabolites were kept normal by infusion of 4–23 IU of insulin during hyperglycaemia. The study confirmed the velocity and magnitude of unstable HbA_1c formation previously found in vitro. The stable HbA_1c formed in 24 h was on average 0.006% of total haemoglobin/ mmol glucose. This compares well with the rate of HbA_1c synthesis reported in normal subjects using ⁵⁹Fe-kinetic measurements, and is in accordance with the concept of slow changes in stable HbA_1c with time and glucose concentration. To investigate the possibility that the rate of HbA_1c synthesis varies with erythrocyte age, glycosylated haemoglobins were measured in erythrocyte fractions after density separation on Percoll-Albumin gradients. We found both in normal subjects and in insulin treated diabetics that the 5% least dense cells contained 70%–80% of whole blood HbA_1c. Assuming the least dense cells to be the youngest erythrocytes, this observation is inconsistent with a slow linear increase in HbA_1c. Similar results were obtained in six newly diagnosed insulin dependent diabetic patients both before and after the first 30 days of insulin treatment, even though a marked decrease in young cell HbA_1c would be expected with the improved glucose control observed. We therefore conclude that density separation of erythrocytes is an inadequate technique to study age related HbA_1c synthesis.