Turk Z, Mesić R, Benko B
University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Zagreb, Croatia.
Clin Chim Acta. 1998 Oct;277(2):159-70. doi: 10.1016/s0009-8981(98)00128-4.
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 HbA1c as the best-studied example. The finding that advanced glycation endproducts are also formed on haemoglobin suggests that HbA1c is a precursor for Hb-AGE formation. HbA1c 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 HbA1c 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 HbA1c values as follows: group I (n = 25) HbA1c < 7%, Hb-AGE = 6.93 (5.7-7.3) U/mg; group II (n = 25) HbA1c = 7-10%, Hb-AGE = 8.62 (7.7-10.2) U/mg; and group III (n = 25) HbA1c > 10%, Hb-AGE = 12.47 (10.8-13.9) U/mg (median (interquartile range)). A close relation between the amounts of red cell HbA1c and Hb-AGE was observed in all diabetic subjects (n = 75) r = 0.77, P < 0.001. Patients with HbA1c level > 8% were considered to be in poor glycaemic control and those with HbA1c < 8% in good control. In the well-controlled subgroup (n = 33), HbA1c and Hb-AGE were less tightly correlated (r = 0.37, P <0.001). However, in those patients with a higher level of HbA1c = 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 HbA1c production and subsequently the rate of Hb-AGE formation. The discrepancy in the correlation between HbA1c 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.
早期糖基化终末产物（AGEs）和晚期糖基化终末产物。早期产物形成的机制已得到充分描述，糖化血红蛋白（HbA1c）是研究得最为透彻的例子。晚期糖基化终末产物也会在血红蛋白上形成，这一发现表明HbA1c是血红蛋白晚期糖基化终末产物（Hb-AGE）形成的前体。HbA1c已被确立为血糖监测的重要指标，但Hb-AGE的诊断作用尚未明确。一个问题是HbA1c和Hb-AGE是竞争性参数还是互补性参数。在我们的研究中，采用竞争性酶联免疫吸附测定（ELISA）技术，使用多克隆抗AGE-核糖核酸酶抗体来检测红细胞溶血产物中沉淀蛋白质的AGE免疫反应性，对Hb-AGE进行定量。结果以AGE单位/毫克血红蛋白表示。根据HbA1c值将三组患者进行分析，具体如下：第一组（n = 25），HbA1c < 7%，Hb-AGE = 6.93（5.7 - 7.3）U/mg；第二组（n = 25），HbA1c = 7 - 10%，Hb-AGE = 8.62（7.7 - 10.2）U/mg；第三组（n = 25），HbA1c > 10%，Hb-AGE = 12.47（10.8 - 13.9）U/mg（中位数（四分位间距））。在所有糖尿病患者（n = 75）中观察到红细胞HbA1c量与Hb-AGE量之间存在密切关系（r = 0.77，P < 0.001）。HbA1c水平> 8%的患者被认为血糖控制不佳，HbA1c < 8%的患者血糖控制良好。在血糖控制良好的亚组（n = 33）中，HbA1c与Hb-AGE的相关性较弱（r = 0.37，P < 0.001）。然而，在HbA1c水平较高的患者中，即HbA1c = 12.55（8.9 - 13.3）%（n = 42），相关的Hb-AGE为11.5（10.3 - 12.8）U/mg血红蛋白，相关性更为显著（r = 0.51，P < 0.001）。Hb-AGE的含量与年龄（r = 0.09）、糖尿病病程（r = 0.05）或视网膜病变和/或肾病的严重程度无关。观察到的差异可能反映了HbA1c产生的动力学速率不同，以及随后Hb-AGE形成的速率不同。HbA1c与Hb-AGE之间相关性的差异表明它们是互补性参数而非对立性参数。与血红蛋白结合的AGEs量与视网膜病变和/或肾病的有无无关。似乎Hb-AGE仅代表代谢状态，无论患者有无糖尿病微血管病变均如此。
