Assessment of the relationship between glucose and A1c using kinetic modeling.
Treatment goals for diabetic patients are directed towards lowering A1c values by controlling blood glucose concentrations (BGC), making it important to understand the relationship between the two parameters. Because findings from clinical trials about the relationship between BGC and A1c values show a profound variability around the obtained regression lines, they are difficult to apply to individual patients. Therefore, a model was developed and applied based on the kinetics of HbA1c formation and removal. It takes the instability of A1c and loss of hemoglobin into consideration. Data from clinical studies and hypothetical scenarios were used to test the model and to describe the relationship between A1c and BGC. A close agreement between experimental and calculated data was obtained in steady-state and non-steady-state conditions. Aside the erythrocyte life span, the chemical instability of A1c appears to affect A1c levels markedly and their changes due to therapy. A threefold increase in BGC over 30 days prior to A1c measurement can cause an increase in A1c value of about 120% as compared with 4% when it occurs 4 months prior to A1c measurement. Profound daily fluctuations in BGC result in minor changes in A1c. In conclusion, A1c provides information about a patient's glycemia, mainly over the past 2 months, and may not reflect well daily blood glucose fluctuations. This model might be suitable to identify individual differences in glycation rates.
Osterman-Golkar
Siv M
SM
Department of Molecular Biology and Functional Genomics, Stockholm University, SE-106 91, Stockholm, Sweden.
Vesper
Hubert W
HW
D000465:Algorithms; D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood*; D006442:Glycated Hemoglobin / Q000493:pharmacokinetics*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D012016:Reference Values
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced