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人血红蛋白A的糖基化。生物动力学模型描述的糖化血红蛋白A1c的动态变化。

Glucosylation of human haemoglobin A. Dynamic variation in HbA1c described by a biokinetic model.

作者信息

Mortensen H B, Vølund A, Christophersen C

出版信息

Clin Chim Acta. 1984 Jan 16;136(1):75-81. doi: 10.1016/0009-8981(84)90249-3.

DOI:10.1016/0009-8981(84)90249-3
PMID:6692567
Abstract

The reaction kinetics for the reversible condensation of D-glucose and haemoglobin A through a labile haemoglobin A-aldimine adduct to HbA1c have been investigated using a biokinetic model. The specific rate constants obtained from in vitro experiments were included in the model which also took into account the removal of HbA1c by decay of erythrocytes. Using a sinusoidal variation in blood glucose a phase delay of about 2 hours was observed between the maximum blood glucose concentration and the maximum aldimine concentration. The mean haemoglobin A-aldimine concentration was independent of both the amplitude and frequency of the blood glucose oscillations and reached equilibrium concentration within 24 hours. The steady state relation between mean blood glucose and HbA1c was similar to the corresponding relation based on an irreversible formation of HbA1c. However, contrary to the irreversible model the steady state HbA1c concentration with the reversible model was reached 3 to 4 weeks after a change in blood glucose level. This finding is in agreement with clinical experience and indicates that in assessing continuous glycaemic control in diabetic patients haemoglobin A1c should be measured approximately every 3 to 4 weeks.

摘要

通过一个生物动力学模型研究了D - 葡萄糖与血红蛋白A通过不稳定的血红蛋白A - 醛亚胺加合物可逆缩合生成糖化血红蛋白A1c的反应动力学。体外实验获得的比速率常数被纳入该模型,该模型还考虑了红细胞衰变对糖化血红蛋白A1c的清除作用。利用血糖的正弦变化,观察到在最大血糖浓度和最大醛亚胺浓度之间存在约2小时的相位延迟。平均血红蛋白A - 醛亚胺浓度与血糖振荡的幅度和频率均无关,并在24小时内达到平衡浓度。平均血糖与糖化血红蛋白A1c之间的稳态关系与基于糖化血红蛋白A1c不可逆形成的相应关系相似。然而,与不可逆模型相反,可逆模型的稳态糖化血红蛋白A1c浓度在血糖水平变化后3至4周达到。这一发现与临床经验相符,表明在评估糖尿病患者的持续血糖控制时,糖化血红蛋白A1c应大约每3至4周测量一次。

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