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In the early 1980s, Henrik Mortensen and colleagues at Glostrup University Hospital, in Denmark, measured the reaction rates in vitro. Their results showed the assumption of irreversibility to be untrue. In fact the reverse reaction (HbA1c to HbA and glucose) proceeds at about 1/8 the rate of the forward reaction, which is very far from irreversible. Mortensen et alia also built a biokinetic model based on the measurements, and validated the model by comparing its predictions to actual patients. See references 3-5. Among other things, Mortensen's work shows that after a change in average bG level, the HbA1c level restabilizes after about 4 weeks. This has several consequences. Clinically, the most important are these: First, the HbA1c is an exponentially weighted average of blood glucose levels from the preceding 4 weeks, with the most recent 2 weeks being by far the most important. Second, measuring HbA1c less often than monthly results in unmonitored gaps between measurements. To use HbA1c as a continuous monitoring tool, you need to check it at least once a month. Third, it is worthwhile checking the HbA1c of newly diagnosed patients as often as once a week to determine the effectiveness of the newly imposed treatment. Reference 1: American Diabetes Association, Tests of Glycemia in Diabetes, Diabetes Care 23:S80-S82, January 2000 Supplement 1. This specific issue is no longer available online, but the most recent version is available at http://diabetes.org/cpr/. Reference 2: Kilpatrick ES, Maylor PW, Keevil BG: Biological Variation of Glycated Hemoglobin. Diabetes Care 21:261-264, February 1998. Abstract available on the web at http://care.diabetesjournals.org/cgi/content/abstract/21/2/261. Reference 3: Mortensen HB, Christophersen C: Glucosylation of human haemoglobin a in red blood cells studied in vitro. Kinetics of the formation and dissociation of haemoglobin A1c. Clinica Chimica Acta 134:317-326, 15 November 1983. Reference 4: Mortensen HB, Volund A, Christophersen C: Glucosylation of human haemoglobin A. Dynamic variation in HbA1c described by a biokinetic model. Clinica Chimica Acta 136:75-81, 16 January 1984. Reference 5: Mortensen HB, Volund A: Application of a biokinetic model for prediction and assessment of glycated haemoglobins in diabetic patients. Scandinavian Journal of Clinical and Laboratory Investigation 48:595-602, October 1988.
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