Personalized Glycated Hemoglobin in Diabetes Management: Closing the Gap with Glucose Management Indicator

Glycated hemoglobin (HbA1c) has played a central role in the management of diabetes since the end of the landmark Diabetes Control and Complications Trial 30 years ago. However, it is known to be subject to distortions related to altered red blood cell (RBC) properties, including changes in cellular lifespan. On occasion, the distortion of HbA1c is associated with a clinical pathological condition affecting RBCs, however, the more frequent scenario is related to interindividual RBC variations that alter HbA1c-average glucose relationship. Clinically, these variations can potentially lead to over- or underestimating glucose exposure of the individual to the extent that may put the person at excess risk of over- or undertreatment. Furthermore, the variable association between HbA1c and glucose levels across different groups of people may become an unintentional driver of inequitable health care delivery, outcomes, and incentives. The subclinical effects within the normal expected physiological range of RBCs can be large enough to alter clinical interpretation of HbA1c and addressing this will help with individualized care and decision making. This review describes a new glycemic measure, personalized HbA1c (pA1c), that may address the clinical inaccuracies of HbA1c by taking into account interindividual variability in RBC glucose uptake and lifespan. Therefore, pA1c represents a more sophisticated understanding of glucose-HbA1c relationship at an individual level. Future use of pA1c, after adequate clinical validation, has the potential to refine glycemic management and the diagnostic criteria in diabetes.