Sickle Cell Trait Skews Hemoglobin A1c Results

PROVIDENCE, RI — Hemoglobin A1c might be underestimating glucose levels in a meaningful percentage of African-American and other patients.

A study published in JAMA points out that HbA1c readings are systematically too low in African-Americans with sickle cell trait, an inherited blood disorder that affects one million to three million Americans and 8% to 10% of African-Americans.1

To determine that, Brown University School of Public Health study retrospectively looked at a cohort of 4,620 African-Americans and found that, for any given fasting or two-hour glucose concentration, individuals with sickle cell trait (SCT) had significantly lower hemoglobin A1c values, 5.72% vs. 6.01%, than those without sickle cell trait.

Drawing from participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS), a study team including researchers from the Providence, RI, VAMC, focused on a cohort that was 61.3% female, mean age 52.3, with 7.9% having SCT.

Results indicate that HbA1c values were statistically significantly lower in those with SCT—5.72%—as opposed to those without—6.01%. Researchers pointed out that their findings were similar in models adjusted for key risk factors and in analyses using 2001 concurrent measures of two-hour glucose and HbA1c concentration for those with SCT vs. without—5.35% compared to 5.65%, a difference of -0.30%.

Furthermore, the study reported that the HbA1c difference by SCT was greater at higher fasting and two-hour glucose concentrations, while the prevalence of prediabetes and diabetes was statistically significantly lower among participants with SCT when defined using HbA1c values.

In 572 observations from participants with SCT and 6,877 observations from participants without SCT, rates were 29.2% vs. 48.6% for prediabetes and 3.8% vs. 7.3% for those with diabetes.

“Among African Americans from 2 large, well-established cohorts, participants with SCT had lower levels of HbA1c at any given concentration of fasting or 2-hour glucose compared with participants without SCT,” study authors concluded. “These findings suggest that HbA1c may systematically underestimate past glycemia in black patients with SCT and may require further evaluation.”

Lacy ME, Wellenius GA, Sumner AE, Correa A, Carnethon MR, Liem RI, Wilson JG, Sacks DB, Jacobs DR Jr, Carson AP, Luo X, Gjelsvik A, Reiner AP, Naik RP, Liu S, Musani SK, Eaton CB, Wu WC. Association of Sickle Cell Trait With

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