SUN-126 Discordantly High Hemoglobin A1c Caused by Hemoglobin Wayne Variant

Abstract

Background: The Hemoglobin A1c is a commonly test used for the diagnosis of diabetes mellitus. It does not require fasting and can be drawn at any time of day, making it more convenient for providers to use as compared to the fasting plasma glucose and the oral glucose tolerance test. Certain pitfalls exist in the use of its measurement. We present a case of a patient who had a falsely elevated HbA1c as a result of an uncommon hemoglobin variant interfering with the measurement. Clinical Case: A 55-year-old Caucasian male was diagnosed with type 2 diabetes mellitus based on A1c value of 10%. He was started on metformin 500 mg twice daily. He subsequently lost 40 pounds through lifestyle modifications. His blood glucose log showed excellent glycemic control with both fasting and pre-prandial blood glucose values mostly running between 80-120 mg/dL. However, his repeat Hb-A1c was 10.5% and 10% three and eight months later using high performance liquid chromatography (HPLC) method. This did not correlate with his current finger blood glucose level. Therefore, he was referred to our clinic for further management. He did not report any hypoglycemic episodes. There was no history of microvascular or macrovascular complications. Basic metabolic panel showed random blood glucose of 98 and a normal creatinine of 0.9 with GFR of > 60. Liver function tests, fasting lipid and CBC were all within the normal range. Serum folic acid, vitamin B12 level and iron studies were also normal. GAD-65 autoantibody and anti-pancreatic islet cell antibodies were negative. Due to the discrepancy between the A1c and the blood glucose levels, more testing was done including Serum fructosamine level which was 224 (0-285) and Hemoglobin electrophoresis. Hemoglobinopathy panel showed Hb-variant consistent with Hb-Wayne. Pattern and concentrations consistent with heterozygous hemoglobin Wayne. He also had a 7 day Continuous glucose monitoring done which showed a Blood glucose average of 95. Repeat Hb-A1c using baronate affinity method was 5.3%. Conclusion: Hemoglobin A1c is a convenient and reliable test for diagnosis of diabetes mellitus and to monitor the impact of management. However, in patients with hemoglobin Wayne variant, there is an overestimation of A1c because of an amino acid substitution that confers a similar charge to A1c. An increased awareness is needed about different Hemoglobin variants which can affect the A1c result. Alternate methods to assess glycemic control will be needed in these cases.