Abstract
Hemoglobin A1c (A1c) is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient’s A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient’s A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his “diabetes management” and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants.
Highlights
Hemoglobin A1c (A1c) became commercially available in 1978, and the American Diabetes Association recommended its use in 1994 to assess the effectiveness of management on glycemic control by providing specific A1c goals.[1]
One could diagnose diabetes mellitus based on 2 consecutive measurements of A1c ≥6.5% with no formal recommendations to confirm the diagnosis with alternative testing, such as fasting plasma glucose (FPG) or an oral glucose tolerance test (OGTT).[5]
We present a case of falsely elevated A1c levels due to a rare hemoglobin variant, which led to the misdiagnosis of diabetes
Summary
Hemoglobin A1c (A1c) became commercially available in 1978, and the American Diabetes Association recommended its use in 1994 to assess the effectiveness of management on glycemic control by providing specific A1c goals.[1]. His fructosamine level was 223 μmol/L (reference range = 0-285 μmol/L), which did not reflect hyperglycemia and was consistent with his home glucose measurements of 92 to 130 mg/dL (fasting and pre/post meals) His A1c continued to be 10% to 11% using the BioRad Variant II high-performance liquid chromatography (HPLC) analysis (Figure 1); further investigation into the cause of this false elevation was done. After revealing the presence of this hemoglobin variant, boronate affinity chromatography was used to measure A1c, which was found to be 4.7% This value was more consistent with reported blood glucose levels and further supported the fact the patient did not have diabetes
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