MKSAP Quiz: Elevated hemoglobin A1c
This month's quiz asks readers to evaluate a 48-year-old woman with type 2 diabetes after laboratory study results show a hemoglobin A1c value of 8.5%.
A 48-year-old woman is evaluated after laboratory study results show a hemoglobin A1c value of 8.5% (estimated average plasma glucose level of 197 mg/dL [10.9 mmol/L]). The patient has type 2 diabetes mellitus. Her blood glucose logs indicate an average fasting and preprandial blood glucose level of 132 mg/dL (7.3 mmol/L) for the past 3 months. She also has a history of iron deficiency anemia secondary to menorrhagia and has recently started iron replacement therapy. Other medications are neutral protamine Hagedorn (NPH) insulin at bedtime and metformin three times daily with meals.
On physical examination, temperature is 36.9 °C (98.4 °F), blood pressure is 127/78 mm Hg, pulse rate is 77/min, and respiration rate is 14/min; BMI is 26. All other findings from the physical examination are unremarkable.
Results of laboratory studies are normal except for a repeat hemoglobin A1c value of 8.5% and a fasting plasma glucose level of 130 mg/dL (7.2 mmol/L); a blood glucose level obtained simultaneously on the patient's glucose monitor is 134 mg/dL (7.4 mmol/L).
Which of the following best explains the discrepancy between her average blood glucose levels as measured on the glucose monitor and her hemoglobin A1c values?
A. Inaccurate glucose monitor
B. Iron therapy
C. Nocturnal hypoglycemia
D. Postprandial hyperglycemia
MKSAP Answer and Critique
The correct answer is D. Postprandial hyperglycemia. This item is available to MKSAP 16 subscribers as item 41 in the Endocrinology section. Information about MKSAP 16 is available online.
The discrepancy in this patient's glucose monitor readings and hemoglobin A1c values is most likely due to postprandial hyperglycemia. She tests her blood glucose level only in a fasting state and before each meal and does not obtain postprandial or other measurements. Although her records indicate an average level that is close to the target of 130 mg/dL (7.2 mmol/L), her blood glucose level may actually exceed 200 mg/dL (11.1 mmol/L) for several hours after meals. These periods of hyperglycemia will contribute to her elevated hemoglobin A1c value. The hemoglobin A1c level represents the average of her fasting, preprandial, postprandial, nocturnal, and other blood glucose levels during the past 3 months.
Although blood glucose monitors occasionally may produce inaccurate readings, this occurrence is extremely rare and also is unlikely in this patient because the simultaneous laboratory plasma glucose level and glucose monitor reading are within 10% of each other.
Hemoglobin A1c levels vary directly with erythrocyte survival. Levels are falsely high when erythrocyte survival is prolonged (decreased erythrocyte turnover), as occurs in patients with untreated iron, vitamin B12, or folate deficiency anemia. Conversely, hemoglobin A1c levels may be falsely low in patients with the shorter erythrocyte survival associated with rapid cell turnover, as occurs in patients with hemolytic anemia; those being treated for iron, folate, or vitamin B12 deficiency; and those being treated with erythropoietin. This patient's history of recent iron deficiency anemia treated with iron is likely to falsely lower, not elevate, her hemoglobin A1c level.
If the patient were having prolonged periods of nocturnal hypoglycemia, she would have a lower-than-expected hemoglobin A1c value.
Key Point
- Average glucose monitor readings that do not include postprandial blood glucose levels are likely to differ from average plasma glucose levels derived from hemoglobin A1c values.