Is Poor Glycemic Control Associated With Reduced Red Blood Cell Lifespan?

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) \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathrm{Erythrocyte\ lifespan}{=}\frac{{[}\mathrm{Hb}{]}(22,400)(\mathrm{blood\ volume})}{0.7(\mathrm{endogenous}\ P\mathrm{\mbox{\textsc{co}}}(64,400)(1,440)(\mathrm{alveolar\ ventilation})}\] \end{document} 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 …