We appreciate the interest of Dagogo-Jack (1) in our study of genetic ancestry and HbA1c in African Americans (2). We interpret his major concerns as follows: 1) HbA1c values may have a glucose-independent genetic component and 2) in our study, adjustment for glucose did not fully account for HbA1c values ≥6.5%.
Our goal was to evaluate if differences in genetic ancestry might explain differences in HbA1c between individuals of African and European ancestry observed in previous studies. Although the heritability of HbA1c approaches 60% in twin studies (3) and “glucose-independent” genetic loci for HbA1c have been found in populations of European descent (4), our results indicate that genetic loci accounting for the heritability of HbA1c are not likely to be population-specific or have large population differences.
After accounting for fasting glucose, we observed a prevalence of undiagnosed diabetes of 4.4% defined by HbA1c ≥6.5% (2), but as in prior studies, including that cited by Dagogo-Jack (5), adjustment for glucose was based on a single measurement and should be distinguished from average glucose (6). The within-person variability of a single glucose measurement is substantially higher than that of HbA1c (7). Thus, we cannot conclude that individuals shifted from the diabetes to the nondiabetes category in our analysis had normal glucose homeostasis. Single HbA1c and glucose measures communicate different information about glucose homeostasis in an individual. The availability of only a single glucose measure is a limitation of many epidemiological studies of glucose homeostasis, and the discrepancy between measures alone does not establish HbA1c as an inferior test.
We agree that our analyses cannot provide a definitive explanation for the black-white difference in HbA1c, but we feel strongly that there is little to suggest a strong genetic ancestral determinant of this difference. Our results support current recommendations for the use of HbA1c to diagnose diabetes in all ethnic groups (8).
No potential conflicts of interest relevant to this article were reported.