A1C: Does One Size Fit All?

  1. Robert M. Cohen, MD
  1. From the Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Cincinnati, Cincinnati, Ohio; and Medical Service, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio
  1. Address correspondence to Robert M. Cohen, MD, University of Cincinnati Medical Center, P.O. Box 670547, Cincinnati, OH 45267-0547. E-mail: robert.cohen{at}uc.edu

Diabetes specialists almost uniformly nod their heads when I ask whether they see patients whose A1C results don't match their blood glucose monitoring data. Providers used to attribute that to unreliability of the monitors or the patient records, but technological advances overcame those barriers. Some mismatches can be attributed to inadequate temporal distribution of glucose sampling, and those will be easier to define as continuous glucose monitoring is used more widely, but a substantial number still remain unexplained. That has led to a controversy as to the role of remaining sources of variation in A1C in the routine patient in whom there is no obvious condition known to influence A1C values, i.e., hemoglobinopathy, red cell disorder, or renal failure known to alter either mean age of circulating red cells or hemoglobin chromatographic properties; or the rare drug that modifies A1C by a variety of mechanisms. Without such pathology, does the fact that such variation remains suggest that our standard A1C goals for glycemic control do not in fact fit all individuals with diabetes? Is it indeed valid to equate A1C and mean blood glucose as has become common?

There is one view that proposes a “high glycator–low glycator” hypothesis (1–9) to explain how apparently equivalent glycemic control could result in differing A1C values. The hypothesis is based on the observation that while most individuals in a population with a given mean blood glucose will have A1C within a fairly narrow expected range, there are subsets who have a consistently higher or consistently lower value. These could be due to corresponding alterations either in the relative rate of intracellular glycation or deglycation or in the rate of hemoglobin (red cell) turnover. How large a problem does this have to be to have widespread clinical implications? Even if only 5% …

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