SOURCE: Lacy ME, Wellenius GA, Sumner AE, et al. Association of sickle cell trait with hemoglobin A1c in African Americans. JAMA 2017;317:507-515.

The recent endorsement of A1c measurements for the diagnosis of diabetes (and prediabetes) has engendered an increasingly frequent diagnosis of both disorders in symptomatic and asymptomatic individuals.

A1c accurately reflects the average exposure of hemoglobin in red blood cells to glucose over the prior 90 days.

However, if red blood cell life is foreshortened — as in hemoglobin S, hemoglobin C, thalassemia, hemolytic anemia, sickle cell disease, and others — there is insufficient red blood cell lifespan for full glycosylation to occur, resulting in a reduced A1c level that does not accurately reflect long-term ambient glucose exposure. Might sickle cell trait affect A1c?

Lacy et al performed a retrospective cohort study from a sample of adults (n = 4,620) that included both A1c and plasma glucose levels. They found that the presence of prediabetes and diabetes was underestimated substantially when A1c was the diagnostic tool in persons with sickle cell trait.

The presence of sickle cell trait appears to lead to lesser levels of hemoglobin glycosylation than occurs in control subjects. The mechanism for this effect is controversial, but may reflect reduced red blood cell lifespan.

Clinicians may wish to include additional diagnostic tests for diabetes in persons with sickle cell trait, such as fasting glucose, postprandial glucose, or oral glucose tolerance testing.