Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, University of Uppsala, PO Box 591, SE-751 24 Uppsala, Sweden.
J Pharmacokinet Pharmacodyn. 2012 Jun;39(3):273-82. doi: 10.1007/s10928-012-9249-1. Epub 2012 Apr 21.
Glycated haemoglobin (HbA1c) concentrations can be falsely lowered in circumstances when red blood cell (RBC) survival is reduced, e.g. in patients with chronic kidney disease (CKD). Glycated albumin (GA) has been suggested as an alternative marker of glycaemic control in these patients since it is independent of the RBC life span. The primary aim of this work was to develop a pharmacokinetic model that describes the time course of GA. The secondary aim was to assess the performance of GA as marker for glycaemic control in comparison to HbA1c based on simulations. For the second aim, three different scenarios were considered in the simulations: 1) assessment of the effect of large intra-day fluctuations in mean blood glucose on GA concentrations, 2) initiation of antidiabetic treatment on the GA profile, and 3) a hypothetical phase II study for a new antidiabetic compound. The GA model, as well as a previously developed HbA1c model described literature data well. GA concentrations appear to be stable even in the presence of high intra-day fluctuations in mean blood glucose concentrations. Simulation of a decrease in mean blood glucose concentrations resulted in a faster change in GA compared to HbA1c. GA also provided a time to 90 % power of the effect of a hypothetical antidiabetic drug that was 16 days shorter than when using HbA1c. These results indicate that GA could be used as alternative marker to assess blood glucose control in diabetic patients with CKD and also to follow an individual patient over time.
糖化血红蛋白（HbA1c）浓度在红细胞（RBC）存活减少的情况下可能会被错误降低，例如在慢性肾脏病（CKD）患者中。由于 GA 独立于 RBC 寿命，因此它被认为是这些患者血糖控制的替代标志物。这项工作的主要目的是开发一种描述 GA 时间过程的药代动力学模型。次要目的是评估 GA 作为血糖控制标志物的性能，与基于模拟的 HbA1c 进行比较。为了实现第二个目标，在模拟中考虑了三种不同的情况：1）评估平均血糖日内波动对 GA 浓度的影响，2）对 GA 曲线进行抗糖尿病治疗，3）对新型抗糖尿病化合物进行假设性 II 期研究。GA 模型以及之前开发的 HbA1c 模型很好地描述了文献数据。即使在平均血糖日内波动较大的情况下，GA 浓度似乎也很稳定。模拟平均血糖浓度降低会导致 GA 比 HbA1c 更快地发生变化。GA 还提供了一种评估假设抗糖尿病药物效果的 90%效力的时间，比使用 HbA1c 时短 16 天。这些结果表明，GA 可用于评估 CKD 糖尿病患者的血糖控制，也可用于随时间跟踪个体患者。
