Falsely Elevated HbA1c Levels in a Patient with Type 2 Diabetes Mellitus and Multiple Beta Globulin Gene Mutations

We present a patient with type 2 diabetes mellitus and a variant hemoglobin whose HbA1c levels were falsely elevated regardless of the measurement method [high-performance liquid chromatography (HPLC), enzymatic, and immuno-assay] used. The causes of the falsely high HbA1c levels in this patient were investigated. The patient was a 73-year-old man with frequent hypoglycemia on self-monitoring of blood glucose, whose HbA1c level when measured by HPLC (standard mode) and immunoassay was substantially higher than that predicted by continuous blood glucose monitoring or from the patient's glycated albumin level. In addition, the HbA1c level measured by immunoassay was significantly higher than the level measured by the HPLC and enzymatic HbA1c assays. A globin gene analysis showed that this patient had Hb Hirose (β-37Trp→Ser) as well as a β-198A→G mutation in the promoter region of the gene. To clarify the causes of this apparently falsely elevated HbA1c level, measurements of in vitro glycation potential and erythrocyte creatine, a marker of red blood cell lifespan, were performed. Although in vitro glycation potential was within normal limits, the red blood cell lifespan was estimated to be 72.7 days (reference range: 55.1-66.7 days). These results suggested that an increased red blood cell lifespan contributed to the high HbA1c levels measured by the various methods used. Increased hemoglobin antigenicity due to the gene mutations in this patient may have contributed to the high HbA1c levels measured by immunoassay.