Kinetics of fast haemoglobin in diabetic rats

This study was designed to examine the appearance and disappearance kinetics of glycosylated haemoglobin during abrupt changes of blood glucose in the rat. The concentration of the fast haemoglobin component, which has similar chromatographic and electrophoretic profiles to human haemoglobin A1, was measured after the induction of diabetes by streptozotocin and its cure by syngeneic intraportal islet transplantation. Fast haemoglobin was increased in 12 diabetic rats compared with 22 controls (15.8 +/- 0.8 versus 8.2 +/- 0.3%, mean +/- SEM). In a group with mild diabetes (n = 8, blood glucose less than 22 mmol/l), fast haemoglobin rose to 13.7 +/- 1.0% by week 8. In a group with severe diabetes (n = 4, blood glucose greater than 22 mmol/l), fast haemoglobin rose more quickly (in 3 weeks) to a higher level (18.2 +/- 3.3%) and changed little thereafter. This suggests a saturable system in which the rate of increase and final value depend upon the degree of hyperglycaemia. After islet transplantation, fast haemoglobin returned to normal in 4 weeks (n = 5, 17.6 +/- 1.4 to 9.4 +/- 0.9%). This delay is shorter than expected from the red cell lifespan (around 60 days), suggesting that haemoglobin glycosylation may be partly reversible. These results suggest that in unstable diabetes the interpretation of haemoglobin A1 levels is not as simple as was supposed previously.