Is Poor Glycemic Control Associated With Reduced Red Blood Cell Lifespan?
- Robert M. Cohen, MD12,
- Robert S. Franco, PHD34 and
- Clinton H. Joiner, MD, PHD45
- 1Division of Endocrinology, Department of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio
- 2Medical Service, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio
- 3Division of Hematology/Oncology, Department of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio
- 4Cincinnati Comprehensive Sickle Cell Center, Cincinnati Children’s Hospital Research Foundation, Cincinnati Ohio
- 5Department of Pediatrics, University of Cincinnati Medical Center, Cincinnati, Ohio
- Address correspondence to Robert M. Cohen, MD, Division of Endocrinology/Metabolism, P.O. Box 670547, Vontz Center for Molecular Studies, 3125 Eden Ave., University of Cincinnati Medical Center, Cincinnati, OH 45267-0547. E-mail: robert.cohen{at}uc.edu
A major assumption in the interpretation of HbA1c as a measure of glycemic control is that the duration of Hb exposure to glucose does not vary among patients who are hematologically
normal. In this issue of Diabetes Care, Virtue et al. (1) use an appealingly simple method to quantitate erythrocyte lifespan (2,3) and report an inverse correlation
with glycohemoglobin concentration in patients with diabetes. They interpret this as a reduced erythrocyte lifespan at higher
blood glucose concentrations. The calculation of erythrocyte lifespan depends on Hb concentration and the amount of carbon
monoxide (CO) in exhaled air and in atmospheric air collected at the subject’s home just after awakening. The principles behind
the method are that heme catabolism is the only endogenous source of CO and that erythrocytes removed from the circulation
are the major source of heme. However, there are multiple assumptions behind the methodology, which may not be met, in the
complicated scenario of diabetes. These all come together in Eq. 1 of Virtue et al. (see [1] for the definition of terms)
which determines erythrocyte lifespan as the inverse of the CO excretion rate, estimating from CO the amount of heme metabolized,
and then the amounts of Hb and, finally, red blood cells removed. Heme is a component not only of Hb but also of cytochromes
and muscle myoglobin, with cytochromes being ubiquitous but particularly enriched in liver. The Hb concentration depends not
only on erythrocyte mass but also on plasma volume; hence, it is sensitive to variations in …
