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It was revealed that in renal failure hemoglobin A1 (HbA1) was formed by the binding of substances other than glucose to Hb. It was elucidated that the formation of HbA1 increased in urea-added medium and further increased in media containing urea either stored at 37 degrees C for 1 week or heated at 100 degrees C for five minutes. The increment of HbA1 was proportional to the amount of cyanic acid produced by the treatment of the medium after the addition of urea. We found that there was the best correlation between the HbA1 level and the BUN level of 1 to 2 weeks before. Therefore, it appeared that HbA1 could be an indicator of the state of renal failure of 1 to 2 weeks earlier in patients with renal failure without impaired glucose tolerance, especially in patients on hemodialysis.

The most abundant minor hemoglobin component of human hemolysate is Hb A1c, which has glucose bound to the N-terminus of the beta chain by a ketoamine linkage. Hb A1c is formed slowly and continuously throughout the 120 day lifespan of the red cell. It can be synthesized in vitro by incubating purified hemoglobin with 14C-glucose. Other minor components, Hb A1a1 and Hb A1a2 are adducts of sugar phosphates at the N-terminus of the beta chain. Hb A1b contains an unidentified nonphosphorylated sugar at the beta N-terminus. In addition, a significant portion of the major hemoglobin component (Hb Ao) is also glycosylated by a glucose ketoamine linkage at other sites on the molecule, including the N-terminus of the alpha chain and the epsilon-amino group of several lysine residues on both the alpha and the beta chains. The results indicate that the interaction of glucose and hemoglobin is rather nonspecific and suggests that other proteins are modified in a similar fashion.