MKSAP quiz: Type 2 diabetes and anemia
This month's quiz asks readers to evaluate a patient with type 2 diabetes, an HbA1c of 7.3%, and a ferritin of 11 ng/mL.
A 35-year-old woman is seen in follow-up evaluation for her type 2 diabetes mellitus. She was diagnosed 3 years ago. She checks her fasting and 2-hour postprandial blood glucose values several times per week. Her fasting blood glucose levels range from 100 to 110 mg/dL (5.5 to 6.1 mmol/L) and her 2-hour postprandial values are 120 to 165 mg/dL (6.7 to 9.1 mmol/L). Her review of symptoms is positive for chronic heavy menses. Medications are metformin and liraglutide.
On physical examination, blood pressure is 123/74 mm Hg and pulse rate is 76/min. BMI is 31.2. The examination is otherwise unremarkable.
Laboratory studies show hematocrit of 33%. Iron studies show a ferritin of 11 ng/mL (11 µg/L), iron of 40 µg/dL (7.2 µmol/L), and total iron-binding capacity of 600 µg/dL (107.4 µmol/L). Her HbA1c is 7.3%.
Which of the following is the most appropriate management of the elevated hemoglobin A1c level?
A. Basal insulin
B. Empagliflozin
C. Ferrous sulfate
D. Hemoglobin electrophoresis
MKSAP Answer and Critique
The correct answer is C. Ferrous sulfate. This item is available to MKSAP 18 subscribers as item 75 in the Endocrinology and Metabolism section. More information about MKSAP 18 is available online.
The most appropriate management for this patient is to initiate ferrous sulfate. This patient has iron-deficiency anemia, a hypoproliferative anemia, which has been shown to erroneously increase the hemoglobin A1c level due to an increase in the proportion of older erythrocytes. Hemoglobin A1c testing measures hemoglobin glycation as a consequence of glucose exposure over the preceding 8 to 12 weeks. Given the patient's age and relatively few comorbidities, her goal hemoglobin A1c level should be less than 6.5% to 7%. Her hemoglobin A1c level is above this goal, but her fingerstick blood glucose data are within her fasting goal of 80 to 130 mg/dL (4.4 to 7.2 mmol/L) and within her 2-hour postprandial goal of less than 180 mg/dL (10 mmol/L) per the American Diabetes Association (ADA) guidelines. Initiating iron supplementation to correct her iron deficiency anemia will increase erythrocyte turnover and shift the proportion toward younger cells, thus allowing a more accurate measurement of glycemic exposure by the hemoglobin A1c to guide therapeutic decisions.
The patient's fasting blood glucose values are within her goal range of 80 to 130 mg/dL (4.4 to 7.2 mmol/L) per the ADA guidelines. Initiating basal insulin based solely on the elevated hemoglobin A1c value with her current fasting blood sugars will increase her risk of hypoglycemia. Similarly, the risk of hypoglycemia is increased by initiating empagliflozin. Increasing the accuracy of the hemoglobin A1c measurement by correcting her iron deficiency anemia should be addressed before considering other drug therapy.
Hemoglobin A1c measurements may be unreliable not only in the setting of anemia, but also in the presence of certain hemoglobinopathies or kidney or liver disease. For example, hemoglobin A1c values may be falsely elevated in patients with hemoglobin F or low with hemoglobin S. However, this patient has an explanation for the discordant hemoglobin A1c and blood glucose results, and the iron deficiency anemia should be the focus of management. Additionally, newer methods of measuring A1c are not altered by the presence of the most common hemoglobinopathies. Therefore, a hemoglobin electrophoresis is not indicated at this time.
Key Point
- Iron-deficiency anemia can erroneously increase the hemoglobin A1c level due to an increase in the proportion of older erythrocytes.