Are There Clinical Implications of Racial Differences in HbA1c? A Difference, to Be a Difference, Must Make a Difference

Abstract

Studies that have compared HbA1c levels by race have consistently demonstrated higher HbA1c levels in African Americans than in whites. These racial differences in HbA1c have not been explained by measured differences in glycemia, sociodemographic factors, clinical factors, access to care, or quality of care. Recently, a number of nonglycemic factors and several genetic polymorphisms that operate through nonglycemic mechanisms have been associated with HbA1c. Their distributions across racial groups and their impact on hemoglobin glycation need to be systematically explored. Thus, on the basis of evidence for racial differences in HbA1c, current clinical guidelines from the American Diabetes Association state: “It is important to take…race/ethnicity…into consideration when using the A1C to diagnose diabetes.” However, it is not clear from the guidelines how this recommendation might be actualized. So, the critical question is not whether racial differences in HbA1c exist between African Americans and whites; the important question is whether the observed differences in HbA1c level are clinically meaningful. Therefore, given the current controversy, we provide a Point-Counterpoint debate on this issue. In the preceding point narrative, Dr. Herman provides his argument that the failure to acknowledge that HbA1c might be a biased measure of average glycemia and an unwillingness to rigorously investigate this hypothesis will slow scientific progress and has the potential to do great harm. In the counterpoint narrative below, Dr. Selvin argues that there is no compelling evidence for racial differences in the validity of HbA1c as a measure of hyperglycemia and that race is a poor surrogate for differences in underlying causes of disease risk.—William T. CefaluEditor in Chief, Diabetes Care

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2018

“…Though conflicting data exists, African Americans may also have higher levels of fructosamine and glycated albumin and lower levels of 1,5-anhydroglucitol, suggesting that their glycemic burden (particularly postprandially) may be higher (18,19). The association of A1C with risk for complications appears to be similar in African Americans and non-Hispanic whites (20,21).…”

Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions

“…There is contention surrounding the influence of race on HbA 1c concentrations. Herman (20) posits that African Americans have higher HbA 1c for any given level of mean glycemia, whereas Selvin (21) argues that the increased mean HbA 1c is a reflection of truly higher mean glycemia in African Americans.…”

“…Yet despite the documented utility of HbA 1c in diabetes research and care, controversies remain. As argued from opposing perspectives by Herman (20) and Selvin (21) in this issue, whether there are clinically significant differences in the relationship between HbA 1c and average glucose in different racial groups remains contested, and similar questions exist about age groups. If there are differences in what HbA 1c “means” in different groups, what are the implications for the diagnosis and management of diabetes?…”

Hemoglobin A1c and Race: Should Therapeutic Targets and Diagnostic Cutoffs Differ among Racial Groups?

“…Some argue that the distinctions are independent of glucose and could impact diagnosis and management of diabetes (6 ). By contrast, others posit that they are due to real differences in blood glucose (7 ). Support for the latter hypothesis is provided by the observations that fructosamine and glycated albumin, which are erythrocyte-independent markers of chronic glycemia, are higher in blacks than whites (7 ).…”

“…Some analyses compared black and white patients with diabetes; racial disparity in glycemic control is well known (7 ). The magnitude of the difference varied considerably among studies, ranging from 0.2% to 2.0% Hb A 1c (4 ).…”