Long-term assessment of glucose control by haemoglobin-AGE measurement

Background Control of blood glucose is important in reducing both the incidence and the severity of complications in diabetes mellitus. One consequence of long-term hyperglycaemia is the formation and accumulation of advanced glycation end-products (AGEs) on tissue macromolecules. An AGE-modified form of human haemoglobin (Hb-AGE), present at high levels in the red cells of diabetic patients, differs from the glucose-derived Amadori product HbA1c in being chemically irreversible and thus persisting for the circulating life of the red cell. We therefore compared Hb-AGE with HbA1c as indicators of long-term blood glucose control. Methods In an open study we measured circulating HbA1c and Hb-AGE concentrations in eight patients with poorly controlled non-insulin-dependent diabetes after a switch to subcutaneous insulin therapy and careful blood glucose monitoring. Results After 16 weeks of insulin therapy, the mean HbA1c had decreased from 13·3 (SD 1·2) to 7·3 (0·9)% and the mean Hb-AGE from 12·1 (1·5) to 7·3 (1·3) U/mg Hb. The rate of Hb-AGE decline was 23% slower than that of HbA1c (p=0·044). Interpretation The observation that Hb-AGE declines more slowly than HbA1c is consistent with the irreversible nature of the AGE product. Because of this property, Hb-AGE may prove superior to HbA1c as a long-term index of circulating glucose concentrations.