A Kinetic Model for Glucose Levels and Hemoglobin A1c Provides a Novel Tool for Individualized Diabetes Management
A Kinetic Model for Glucose Levels and Hemoglobin A1c Provides a Novel Tool for Individualized Diabetes Management
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DOI：
10.1177/1932296819897613
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发表时间：
2021-03-01
影响因子：
5
通讯作者：
Ajjan, Ramzi A.
中科院分区：
文献类型：
--
作者：
Xu, Yongjin;Dunn, Timothy C.;Ajjan, Ramzi A.
背景：定期评估糖化血红蛋白 (HbA1c) 对于糖尿病患者的管理至关重要。连续血糖监测 (CGM) 估算的 HbA1c (eHbA1c) 已被提议作为反映实验室 HbA1c 的衡量标准。然而，两种标记物之间的差异很常见，限制了 eHbA1c 的临床使用。因此，开发更好地反映实验室 HbA1c 的血糖生成器将在糖尿病管理中高度相关。方法：使用之前对 120 名糖尿病患者进行的两项临床研究的 CGM 数据，我们得出了一种新颖的动力学模型，该模型考虑了红细胞 (RBC) 周转、跨膜葡萄糖转运和血红蛋白糖化过程，以个体化血糖水平和 HbA1c 之间的关系。结果：使用 CGM 数据和两项实验室 HbA1c 测量值、动力学速率常数计算红细胞糖化和周转率。这些速率常数用于预测未来的 HbA1c，创建一种新的个体化血糖标记物，称为计算 HbA1c (cHbA1c)。与 eHbA1c 相比，新的血糖标记物 cHbA1c 可以准确估计个体的实验室 HbA1c。该模型和数据证明了实验室 HbA1c 与稳态血糖之间存在非线性关系，并且还表明糖化状态受年龄的调节。结论：我们的动力学模型为葡萄糖水平与糖化血红蛋白之间的关系提供了机制见解。因此，新的血糖标志物不仅能准确反映实验室HbA1c，而且提供了新的概念来解释某些个体中HbA1c与平均血糖不匹配的机制，这对未来的临床管理具有重要意义。
Background: Regular assessment of glycated hemoglobin (HbA1c) is central to the management of patients with diabetes. Estimated HbA1c (eHbA1c) from continuous glucose monitoring (CGM) has been proposed as a measure that reflects laboratory HbA1c. However, discrepancies between the two markers are common, limiting the clinical use of eHbA1c. Therefore, developing a glycemic maker that better reflects laboratory HbA1c will be highly relevant in diabetes management.Methods: Using CGM data from two previous clinical studies in 120 individuals with diabetes, we derived a novel kinetic model that takes into account red blood cell (RBC) turnover, cross-membrane glucose transport, and hemoglobin glycation processes to individualize the relationship between glucose levels and HbA1c.Results: Using CGM data and two laboratory HbA1c measurements, kinetic rate constants for RBC glycation and turnover were calculated. These rate constants were used to project future HbA1c, creating a new individualized glycemic marker, termed calculated HbA1c (cHbA1c). In contrast to eHbA1c, the new glycemic marker cHbA1c gave an accurate estimation of laboratory HbA1c across individuals. The model and data demonstrated a non-linear relationship between laboratory HbA1c and steady-state glucose and also showed that glycation status is modulated by age.Conclusion: Our kinetic model offers mechanistic insights into the relationship between glucose levels and glycated hemoglobin. Therefore, the new glycemic marker does not only accurately reflect laboratory HbA1c but also provides novel concepts to explain the mechanisms for the mismatch between HbA1c and average glucose in some individuals, which has implications for future clinical management.