Hemoglobin A1c (Hb A1c) is the standard test for assessing glycemic control over the immediately previous 3-month period (life span of a red blood cell). An increased Hb A1c value (i.e., ≥6.5%) has also recently been approved by the American Diabetes Association as diagnostic for diabetes. In the case presented, a diagnostic Hb A1c test was ordered to distinguish the prediabetic state of impaired fasting glucose from overt diabetes. The commonly used cation-exchange HPLC Hb A1c assay reported a spuriously high Hb A1c value of 115.8% (reference interval, 4%–6%), which alerted the healthcare team and prompted an investigation. The authors' data demonstrated that the patient's falsely increased Hb A1c value was consistent with the presence of a hemoglobin variant, Hb Raleigh, which falsely increased the chromatogram band usually attributable to Hb A1c. For people with hemoglobinopathies, some Hb A1c assays give falsely high (or low) readings that can lead to the overtreatment or undertreatment of diabetes, respectively (see the National Glycohemoglobin Standardization Program Web site http://www.ngsp.org/interf.asp). In addition to hemoglobinopathies, disorders of erythrocyte life span are also common situations in which HbA1c, although accurately measured with conventional assays, falsely reflects glycemic control. Rapid red blood cell turnover (i.e., hemolysis or blood loss) and a prolonged red blood cell life span (i.e., kidney diseases) alter the time available for glycation, and these processes can produce Hb A1c values that underestimate or overestimate, respectively, glycemic control. Healthcare providers should be vigilant in suspecting hemoglobinopathies or erythrocyte life span disorders when (a) the Hb A1c value is discordant with the patient's recorded serum glucose concentrations or clinical presentation, (b) an Hb A1c result is >15%, or (c) Hb A1c test results change radically between assays. For situations in which Hb A1c values are unreliable, measurements of fructosamine, frequent daily glucose testing, or continuous glucose-monitoring systems should be used to monitor glycemic control more accurately in people with diabetes.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:
Employment or Leadership: None declared.
Consultant or Advisory Role: None declared.
Stock Ownership: None declared.
Honoraria: S.J. Fisher, Merck.
Research Funding: None declared.
Expert Testimony: None declared.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- Received for publication November 5, 2010.
- Accepted for publication November 16, 2010.
- © 2010 The American Association for Clinical Chemistry