(10.11) Uncovering Hemoglobinopathy: An Unexpected Benefit of Diabetes Technology

Diabetes technology, specifically continuous glucose monitoring (CGM), has provided patients and clinicians across the globe valuable insight into glycemic trends and patterns. When CGM data is reviewed and interpreted by the clinician, it is not uncommon to identify discordance between the glucose management indicator (GMI) on the CGM report and real-world. We know that there are many factors that can knowingly contribute to discordant A1c versus CGM data, including sickle cell disease, pregnancy, glucose-6-phosphate dehydrogenase deficiency, hemodialysis, recent blood los or transfusion, or hemoglobin variants. Here we describe two cases where hemoglobin irregularities led to discordance between A1c and CGM, including one case where a rare hemoglobinopathy variant was found as a result of CGM use.

Case(s) Description :

Mr. P was seen in outpatient consultation for diabetes management in November 2019 with an A1c of 8.8% (estimated average glucose 206mg/dL). A reliable historian, he describes home glucose values generally less than 200mg/dL. CGM was implemented and on return visit in March 2020 it was found that he had 14-day average glucose 119mg/dL, A1c 7.0% (estimated average glucose 154mg/dL) and fructosamine 237mcmol/L (A1c 5-6%). Glycemia on CGM correlated with random glucose samples available for review in laboratory, confirming reliability. On intensive chart interrogation, it was found that Mr. P was diagnosed with beta thalassemia minor via hemoglobin electrophoresis in 2000 which is believed to be the cause for his discordant A1c.

Ms. K was seen for outpatient consult for diabetes management in September 2021 with an A1c of 10.4% (estimated average glucose 252mg/dL). She was surprised by the diagnosis because she followed a healthy diet and had worked out regularly most of her life. She was started on metformin and CGM. She returned in October 2021 with a 28 day average BG of 97mg/dL on her CGM. This was confirmed on labs with fasting blood sugars ranging from 87-100mg/dL. Despite this, her A1c was found to be persistently elevated at 10.3%. A fructosamine and hemoglobinopathy evaluation were then ordered with the fructosamine resulting at 242mcmol/L (A1c 5-6%) and her hemoglobinopathy panel revealing a mutation known as Hemoglobin Wayne which has been previously described in the literature as a potential cause of falsely elevated A1c. Metformin was stopped and patient was referred to hematology for further workup and treatment of her hemoglobinopathy.

Discussion :

Hemoglobinopathies can cause discordance between A1C and CGM. When patients present with mismatch between CGM and A1c values with no known reason for the discordance, further evaluation including hemoglobin electrophoresis could be prudent. While uncovering a hemoglobinopathy via CGM may not inform changes to diabetes management directly, it may provide pertinent information for the patient, clinician and broader healthcare team.