title: Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation.
abstract: HbA1c is commonly used to monitor glycemic control. However, there is growing evidence that the relationship between HbA1c and mean blood glucose (MBG) is influenced by variation in red blood cell (RBC) lifespan in hematologically normal individuals. Correction of HbA1c for mean RBC age (MRBC ) requires a noninvasive, accurate, and affordable method to measure RBC survival. In this study, we evaluated whether a stable isotope approach would satisfy these requirements. RBC lifespan and MRBC were determined in a group of nine hematologically normal diabetic and nondiabetic subjects using oral (15) N-glycine to label heme in an age cohort of RBC. The MRBC was 58.7 ± 9.1 (2SD) days and RBC lifespan was 106 ± 21 (2SD) days. This degree of variation (±15-20%) is consistent with previous studies using other techniques. In a subset of seven subjects, MRBC determined with the biotin label technique were available from approximately five years prior, and strongly correlated with the stable isotope values (R(2) = 0.79). This study suggests that the MRBC is stable over time but varies substantially among individuals, and supports the importance of its variation in HbA1c interpretation. The characteristics of the stable isotope method support its suitability for studies to directly evaluate the impact of variation in MRBC on the interpretation of HbA1c.
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Paramjit K
authors.initials: PK
authors.lastname: Khera
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Smith
authors.affiliation: Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lindsell
authors.affiliation: Department of Medicine, Cincinnati VA Medical Center, Cincinnati, OH.
authors.forename: Mary Colleen
authors.initials: MC
authors.lastname: Rogge
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Haggerty
authors.affiliation: Metabolic Solutions, Inc, Nashua, New Hampshire.
authors.forename: David A
authors.initials: DA
authors.lastname: Wagner
authors.affiliation: Division of Hematology, Department of Internal Medicine, University of Cincinnati College of Medicine.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Palascak
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, Georgia.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Hibbert
authors.affiliation: Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, Georgia.
authors.forename: Clinton H
authors.initials: CH
authors.lastname: Joiner
authors.affiliation: Division of Hematology, Department of Internal Medicine, University of Cincinnati College of Medicine.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Franco
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.|Department of Medicine, Cincinnati VA Medical Center, Cincinnati, OH.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cohen
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D002470:Cell Survival; D016922:Cellular Senescence; D003920:Diabetes Mellitus / Q000097:blood*; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D005998:Glycine / Q000008:administration & dosage* / Q000737:chemistry; D006418:Heme / Q000737:chemistry; D006801:Humans; D008297:Male; D009587:Nitrogen Isotopes
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D005998:Glycine; D006418:Heme; D009587:Nitrogen Isotopes; C517652:hemoglobin A1c protein, human