Validation of a hemoglobin A1c model in patients with type 1 and type 2 diabetes and its use to go beyond the averaged relationship of hemoglobin A1c and mean glucose level

Journal of Translational Medicine

Jerzy Kawiak²  Janusz Krzymien¹  Stanislawa Sabalinska²  Marianna I Bak¹  Piotr Foltynski²  Piotr Ladyzynski² 

[1] Clinic and Department of Gastroenterology and Metabolic Diseases, Medical University of Warsaw, 1A Banacha street, Warsaw, 02-097, Poland;Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 4 Trojdena street, Warsaw, 02-109, Poland

关键词: Cultivation of erythrocytes in vitro;    Continuous glucose monitoring;    Chronic glycemia;    Glycemic control;    Diabetes management;    Glycated hemoglobin A1c;    Diabetes mellitus;   

Others  :  1146894
DOI  :  10.1186/s12967-014-0328-5

 received in 2014-07-14, accepted in 2014-11-12,  发布年份 2014

【 摘 要 】

Background

Glycated hemoglobin A_1c (HbA_1c) has been used as an index of glycemic control in the management, guidance, and clinical trials of diabetic patients for the past 35 years. The aim of this study was to validate the HbA_1c model in patients with type 1 and type 2 diabetes and to use it to support interpretation of HbA_1c in different clinical situations.

Methods

The HbA_1c model was identified in 30 patients (15 with type 1 diabetes and 15 with type 2 diabetes) by estimating the overall glycation rate constant (k), based on results of continuous glucose monitoring. The model was validated by assessing its ability to predict HbA_1c changes in cultures of erythrocytes in vitro and to reproduce results of the A1C-Derived Average Glucose (ADAG) study. The model was used to simulate the influence of different glucose profiles on HbA_1c.

Results

The mean k was equal to 1.296 ± 0.216 × 10⁻⁹ l mmol⁻¹ s⁻¹ with no difference between type 1 and type 2 diabetes. The mean coefficient of variation of k was equal to 16.7%. The model predicted HbA_1c levels in vitro with a mean absolute difference less than 0.3% (3.3 mmol/mol). It reproduced the linear relationship of HbA_1c and mean glucose levels established in the ADAG study. The simulation experiments demonstrated that during periods of unstable glycemic control, glycemic profiles with the same mean glucose might result in much different HbA_1c levels.

Conclusions

Patients with type 1 and type 2 diabetes are characterized by the same mean value of k, but there is considerable interindividual variation in the relationship of HbA_1c and mean glucose level. Results suggest that reciprocal changes in glycation rate and the life span of erythrocytes exist in a wide range of HbA_1c values. Thus, for an average patient with diabetes, no modifications of parameters of the glycation model are required to obtain meaningful HbA_1c predictions. Interpreting HbA_1c as a measure of the mean glucose is fully justified only in the case of stable glycemia. The model and more frequent tests of HbA_1c might be used to decrease ambiguity of interpreting HbA_1c in terms of glycemic control.

【 授权许可】

   
2014 Ladyzynski et al.; licensee BioMed Central Ltd.

【 图 表 】

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