The case of the unreliable HbA1c — Part One

I saw a 42-year-old man with type 1 diabetes in consultation. He has mild peripheral neuropathy but no evidence of nephropathy or active retinopathy. He also has primary hypothyroidism and fibromyalgia. He has been on continuous subcutaneous insulin infusion pump therapy for the last three years. He is very pleased with the improvement in his finger stick blood glucoses but has been frustrated that his HbA1c remains elevated.

He tests four to eight times a day. His fasting and pre-meal blood glucoses have rarely been above 130 mg/dL. He only occasionally has postprandial hyperglycemic excursions, usually due to dietary indiscretion. However, despite excellent glycemic control as documented by his finger stick glucoses, his HbA1c has remained in the 10% to 11% range. We performed continuous glucose monitoring which failed to reveal any unidentified hyperglycemia. A fructosamine was 281 mcmol/L suggesting an average plasma glucose of about 145 mg/dL over the past few weeks. I suspect that rather than poor long-term glycemic control, his hemoglobin A1c is inaccurate.

Hemoglobin A1c can be unreliable in several settings. A number of abnormal hemoglobin variants have been reported to affect HbA1c. Hemolytic anemia and transfusions can falsely lower HbA1c. Medications such as erythropoietin can influence HbA1c. Finally, HbA1c may be falsely elevated in iron deficiency anemia.

On further questioning, the patient mentioned to me that he had had anemia for years. No one had been able to determine the cause. He denied blood in his stool. He had upper and lower endoscopy and was diagnosed with gastritis. At one point, he had been given parenteral iron. However, he had a reaction and received no further doses. He has been taking oral iron supplementation but has continued to be anemic.

I ordered CBC which revealed a microcytic anemia. His hemoglobin was 9.8 and platelets were elevated. Additional studies confirmed iron deficiency. I explained to him that the hemoglobin A1c was falsely elevated due to the iron deficiency anemia. Based on his blood glucoses values and fructosamine, I expect that his true HbA1c would be lower than his measured HbA1c.

The question is: why does he have iron deficiency anemia?

To be continued…