Falsely Elevated A1C with Euglycemia in a Patient Without Diabetes

Euglycemia: Clinical Relevance/Discussion

A strict quality control program has improved the precision and accuracy of assays in the United States and many international assays. The National Glycohemoglobin Standardization Program (NGSP)’s standardization of HbA_1c test results to pivotal trials like the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) established the direct relationship between HbA_1c levels and disease outcomes in patients with diabetes.^5-8 Although the international standardization of the HbA_1c assay has greatly decreased the potential for technical errors in interpreting HbA_1c results, biologic and patient-specific factors may cause misleading results.  

Certain hemoglobin variants and conditions have been shown to affect red cell lifespan and hence may lead to false HbA_1c results. Conditions linked to falsely elevated HbA_1c levels include anemias associated with decreased red blood cell turnover, asplenia, uremia, severe hypertriglyceridemia (>1750 mg/dL), severe hyperbilirubinemia (>20 mg/dL), lead poisoning, and chronic ingestion of alcohol, salicylates, and opioids.³

Conversely, conditions that could lead to a falsely decreased HbA_1c include anemia from acute or chronic blood loss, splenomegaly, pregnancy, and red blood cell transfusion. Additionally, ingestion of vitamin E, ribavirin, and interferon-alpha may be associated with falsely lowered HbA_1c.³ Hemoglobin variants and vitamin C ingestion can falsely increase or decrease HbA_1c depending on method and assay used.^3,8,9

As the HbA_1c depends on the lifespan and morphology of red blood cells, a hemoglobin fractionation was performed for this patient, which revealed mild alpha thalassemia. Alpha thalassemia is one of the hemoglobin variants that may falsely elevate or reduce HbA_1c measurement depending on the method and assay used due to analytical, biochemical, and biologic factors.³

Thus, while the HbA_1c is a generally well-accepted parameter used for diagnosis of diabetes mellitus and to estimate the degree of glycemia, there are factors that can falsely increase or decrease the test result. Fortunately, as this patient’s glucose levels were not elevated despite the high HbA_1c result, the patient did not receive any oral or injectable antihyperglycemic medications. The use of continuous glucose monitoring devices can make the identification of within-day and between-day glycemic variations easier and allow for identification of falsely elevated HbA_1c results such as those presented in this clinical case.

Conclusion

Intensive insulin therapy effectively delays the onset and slows the progression of microvascular complications in patients with diabetes.^5,8,10 Although the international standardization of the HbA_1c assay has decreased the potential for technical errors in interpreting HbA_1c results, other biologic and patient-specific factors may cause misleading results. These factors should continually be kept in mind as falsely elevated HbA_1c or lowered HbA_1c result could lead to underuse or misuse of antihyperglycemic medications.

Florence O. Awosika, DNP, FNP-BC, CDCES, is an endocrinology nurse practitioner provider at the Walter Reed National Military Medical Center in Bethesda, Maryland.

References

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This article originally appeared on Clinical Advisor