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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4284-4291.
Prepublished online as a Blood First Edition Paper on August 11, 2008; DOI 10.1182/blood-2008-04-154112.
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Submitted April 28, 2008
Accepted August 2, 2008
Red cell lifespan heterogeneity in hematologically normal people is sufficient to alter HbA1c
Robert M Cohen*, Robert S. Franco, Paramjit K. Khera, Eric P. Smith, Christopher J. Lindsell, Peter J. Ciraolo, Mary B. Palascak, and Clinton H. Joiner
Division of Endocrinology, Diabetes and Metabolism; Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
Cincinnati Comprehensive Sickle Cell Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States
Division of Emergency Medicine; Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
Division of Hematology/Oncology; Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
Department of Pediatrics; Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States
* Corresponding author; email: robert.cohen{at}uc.edu.
Though red blood cell (RBC) lifespan is a known determinant of percent HbA1c, its variation has been considered insufficient to affect clinical decisions in hematologically normal individuals. However, an unexplained discordance between HbA1c and other measures of glycemic control can be observed that could be due in part to differences in RBC lifespan. To explore the hypothesis that variation in RBC lifespan could alter measured HbA1c sufficiently to explain some of this discordance, we determined RBC lifespan using a biotin label in six people with diabetes (DM) and six non-DM controls (NDM). Mean RBC age was calculated from the RBC survival curve for all the circulating RBC and also for the labeled RBC at multiple time points as they aged. In addition, the HbA1c in magnetically-isolated labeled RBC and in isolated transferrin receptor positive (TfR(+)) reticulocytes were used to determine the in vivo synthetic rate of HbA1c. The mean age of circulating RBCs ranged 39-56 days in DM and 38-60 days in NDM subjects. HbA1c synthesis was linear and correlated with mean whole blood HbA1c (R2 = 0.91). The observed variation in RBC survival was large enough to cause clinically important differences in HbA1c for a given mean blood glucose.
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