Misuse of Race in the Interpretation of HbA1c

OverviewHemoglobin A1c (HbA1c) is a diagnostic test for diabetes and the standard glycemic measure used to monitor glycemic control.Arising from observations of racial differences in the absolute levels of HbA1c, guidelines and experts have recommended that race or ethnicity be "taken into consideration" when using HbA1c to diagnose diabetes or make treatment decisions (1).Some experts have stated that HbA1c is a "less accurate" or "inappropriate" diagnostic test in certain racial or ethnic groups and there have been numerous calls for the use of race-specific HbA1c cut-points.However, such recommendations raise concerns about the inappropriate use of race as a biological variable and should be re-visited in light of recent calls for removal of race or ethnicity from screening recommendations and clinical equations (2). Racial Differences in HbA1cIndividuals who identify as Black or African American have higher average HbA1c as compared to individuals who identify as non-Hispanic White, even after adjusting for glucose measures (3).Persons who self-report Hispanic ethnicity tend to have HbA1c levels that are intermediate between White and Black individuals (4).These racial differences are small, typically ~0.3 %-points HbA1c (3); similar in magnitude to methodological error of many HbA1c assays. Factors Underlying Racial Differences in HbA1cGenetic factors that influence HbA1c differ by ancestry (5).For example, hemoglobin S (sickle cell trait), hemoglobin C, and G6PD affect red cell turnover and are more common in persons of African or South Asian descent.These variants lower HbA1c.Recently, a novel structural (non-coding) variant has been reported that is present in ~30% of African Americans but <1% White adults.This variant is associated with higher HbA1c (6).It