Comparison of advanced glycation endproducts on haemoglobin (Hb-AGE) and haemoglobin A(1c) for the assessment of diabetic control

Glycation process in vivo results in two different products: early and adva nced glycation endproducts (AGEs). The mechanism of early product formation has been well described, with HbA(1c) as the best-studied example. The fin ding that advanced glycation endproducts are also formed on haemoglobin sug gests that HbA(1c) is a precursor for Hb-AGE formation. HbA(1c) has been we ll established as an important indicator for glycaemia monitoring, but the diagnostic role ;of Hb-AGE has not yet been clarified. A question is whethe r HbA(1c) and Hb-AGE are competitive or complementary parameters. In our st udy, Hb-AGE was quantified by the competitive ELISA technique using polyclo nal anti-AGE-RNase antibodies to detect AGE immunoreactivities of proteins precipitated in red cell hemolysate. Results are expressed as AGE units/mg Hb. Hb-AGE was analysed in three groups of patients divided according to Hb A(1c) values as follows: group I (n = 25) HbA(1c) < 7%, Hb-AGE = 6.93 (5.7- 7.3) U/mg; group II (n = 25) HbA(1c) = 7-10%, Hb-AGE = 8.62 (7.7-10.2) U/mg ; and group III (n = 25) HbA(1c) >10%, Hb-AGE = 12.47 (10.8-13.9) U/mg (med ian (interquartile range)). A close relation between the amounts of red cel l HbA(1c) and Hb-AGE was observed in all diabetic subjects (n = 75) r = 0.7 7, P < 0.001. Patients with HbA(1c) level >8% were considered to be in poor glycaemic control and those with HbA(1c) <8% in good control, In the well- controlled subgroup (n = 33), HbA(1c) and Hb-AGE were less tightly correlat ed (r = 0.37, P < 0.001). However, in those patients with a higher level of HbA(1c) = 12.55 (8.9-13.3)% (n = 42), the related Hb-AGE was 11.5 (10.3-12 .8) U/mg Hb, yielding a more significant correlation (r = 0.51, P < 0.001). The content of Hb-AGE did not correlate with age (r = 0.09), diabetes dura tion (r = 0.05) or severity of retinopathy and/or nephropathy. The observed difference may reflect a different kinetic rate of HbA(1c) production and subsequently the rate of Hb-AGE formation. The discrepancy in the correlati on between HbA(1c) and Hb-AGE suggests that they are complementary rather t han opposed parameters. The amount of haemoglobin-linked AGEs does not corr elate with the presence or absence of retinopathy and/or nephropathy. It se ems that Hb-AGE represents only the metabolic status, equally in the subjec ts with and without diabetic microangiopathy. (C) 1998 Elsevier Science BN. All rights reserved.