Why is it important to focus on African Americans with sickle cell who also have type 2 diabetes?

Sickle cell disease (SCD) is an autosomal, recessive hemoglobinopathy that occurs when an individual inherits two copies of the defective beta hemoglobin gene. This is different from sickle cell trait (SCT), in which an individual inherits a single copy of the gene that causes SCD. In the United States, SCD and SCT are extremely rare in white individuals, but 8%–10% of African Americans carry the mutated beta hemoglobin gene and 1 in 375 has full-blown SCD. Among non-Hispanic African Americans age 20 or older, 13.2% also have diabetes, compared with only 7.6% of non-Hispanic whites. As a result, there is a greater risk of SCD/SCT interfering with diabetes screening and management in African Americans.

How does SCD/SCT impact hemoglobin A1c (HbA1c) testing?

HbA1c measurements typically reflect a patient’s average blood glucose levels over a period of 90–120 days, which is the normal lifespan of a red blood cell (RBC). However, the relationship of HbA1c with blood glucose levels may differ between African Americans with and without SCD/SCT. This is because sickle cells have a much shorter lifespan of only 10–20 days. Shorter RBC survival results in less time for hemoglobin to be exposed to glycation, reducing HbA1c concentration.

In one study, an African American woman with both SCD and type 2 diabetes had blood glucose levels ranging from 50 to 320 mg/dL, yet her HbA1c was consistently less than 6% (Ann Pharmacother 2005;39:1557–60). In another retrospective cohort study of 4,620 African Americans, for any given fasting or 2-hour glucose concentration, individuals with SCT had significantly lower HbA1c values than those without SCT (5.72% vs. 6.01%) (JAMA 2017;317:507–15).

In most current HbA1c assays, hemoglobin variants prevalent in SCD patients such as HbS or HbF do not cause interference. However, HbA1c assays can’t account for the difference in RBC survival that occurs with hemoglobinopathies. Further compounding this issue is evidence suggesting that at a given glucose concentration, white individuals actually have overall lower HbA1c levels than those of African descent. Other factors related to SCD/SCT such as iron deficiency anemia can also affect HbA1c measurements.

How can labs diagnose and monitor diabetes in patients with SCD/SCT?

Among African Americans with SCD/SCT, HbA1c results may underestimate past glycemia and should be evaluated further. It may be beneficial for laboratories to test African American patients with type 2 diabetes for SCD/SCT and document the results in patients’ medical records.

According to the American Diabetes Association’s recommendations, fructosamine testing is an alternative to HbA1c testing in patients who have a shortened RBC lifespan or hemoglobin variants that prevent HbA1c from being reliably measured. Though fructosamine only assesses blood glucose levels over a period limited to 2–3 weeks, multiple studies have demonstrated moderate to strong correlation with HbA1c and recommend the use of this test. Quarterly monitoring of glycemic control using fructosamine in SCD/SCT patients will provide more reliable information than HbA1c. This ensures meticulous evaluation of patient-specific blood glucose levels and helps create patient-tailored treatment regimens.

Chesinta B. Voma, PhD, is the technical director at the Cleveland HeartLab in Ohio. +Email: chesinta@yahoo.com