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

Abstract

Glycation process in vivo results in two different products: early and advanced glycation endproducts (AGEs). The mechanism of early product formation has been well described, with HbA 1c as the best-studied example. The finding that advanced glycation endproducts are also formed on haemoglobin suggests that HbA 1c is a precursor for Hb-AGE formation. HbA 1c has been well established as an important indicator for glycaemia monitoring, but the diagnostic role of Hb-AGE has not yet been clarified. A question is whether HbA 1c and Hb-AGE are competitive or complementary parameters. In our study, Hb-AGE was quantified by the competitive ELISA technique using polyclonal 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 HbA 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 (median (interquartile range)). A close relation between the amounts of red cell HbA 1c and Hb-AGE was observed in all diabetic subjects ( n=75) r=0.77, 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 correlated ( 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 duration ( 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 correlation between HbA 1c and Hb-AGE suggests that they are complementary rather than opposed parameters. The amount of haemoglobin-linked AGEs does not correlate with the presence or absence of retinopathy and/or nephropathy. It seems that Hb-AGE represents only the metabolic status, equally in the subjects with and without diabetic microangiopathy.