Exhaled Carbon Monoxide and Red Blood Cell Turnover

Hemoglobin A1C (HbA1c) is the cornerstone of blood sugar monitoring. As HbA1c is formed by the covalent reaction of glucose with hemoglobin throughout the lifespan of the red blood cell (RBC), it is used as a surrogate marker for integrated mean blood glucose over time. The HbA1c value therefore is dependent on the average amount of time the RBC spends in the circulation (mean RBC age or MRBC). However, our previous studies measuring red cell lifespan using either an age cohort label (ex vivo labeling with biotin) or a population label (stable isotope) have demonstrated, contrary to established dogma, that the MRBC varies substantially among individuals and is sufficiently variable to affect HA1c interpretation in a significant percentage of individuals with diabetes. Although the stable isotope method is suitable for clinical studies, it has limited potential for application to large population of subjects. A potential alternative to the stable isotope approach that could be applied routinely to the average patient in the clinic is measurement of exhaled carbon monoxide (eCO) concentration, a reflection of RBC heme turnover. In general, the primary advantage of applying exhaled breath analyses to human clinical diagnostics and therapeutic monitoring is that this technique is noninvasive, safe, simple, and provides near-real time measurements. The purpose of this observational study is to optimize the collection of eCO in a normal control population followed by measurement in a cohort of subjects previously assessed by either the SI or biotin methods for comparison.