David M. Nathan, MD; Hui Zheng, PhD
Potential Conflicts of Interest: None disclosed.
Nathan D., Zheng H.; Does the Relationship Between Hemoglobin A1c and Mean Glucose Levels Differ by Race?. Ann Intern Med. 2010;153:847-848. doi: 10.7326/0003-4819-153-12-201012210-00014
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Published: Ann Intern Med. 2010;153(12):847-848.
TO THE EDITOR:
The glycated hemoglobin (HbA1c) assay has been widely accepted as an objective index of chronic glycemia, is universally used for diabetes management (1), and has now been recommended for diagnosis (2). The mathematical relationship between HbA1c and mean glucose levels was established in the 1980s by small studies that compared self-monitored glucose levels over 5 to 8 weeks and HbA1c level measured at the end of that period (1). Recent studies have used more comprehensive measures, such as continuous glucose monitoring, to determine the relationship (3, 4). These studies have demonstrated relatively higher correlation coefficients (R > 0.9) than those in previous studies with less frequent monitoring, emphasizing the need for comprehensive measures of glucose to capture true mean glycemia and accurately determine the relationship between mean glucose levels and HbA1c. The largest such study was the ADAG (A1c-Derived Average Glucose) Study (4). Unfortunately, only 8% of the ADAG population was African or African American, and power was limited to appreciate whether the relationship between mean glucose and HbA1c differed among races. The difference in regression lines of mean glucose on HbA1c between the non-Hispanic white and African American cohorts had a P value of 0.07. At the low (diagnostic) end of the glycemic spectrum, HbA1c level for a similar mean glucose level was minimally higher (<0.13%) for African American persons than for non-Hispanic white persons. This borderline significant difference between races in the relationship between mean glucose and HbA1c has been used to support the notion that HbA1c levels differ for similar levels of mean glycemia in different races (5). Several cross-sectional studies, including the recent study by Ziemer and colleagues (6), have been published supporting this conclusion; however, they have relied on very limited glucose measurements, ranging from a single timed glucose level to a single glucose tolerance test, to measure “mean glucose.” These studies ignore the well-recognized variability in intrapatient, interday glucose values and the possibility that sampling error might explain their findings. Specifically, none of the investigators has considered that everyday glucose levels might differ between different racial groups, independent of the limited glucose levels on the day of testing. Whether the relationship between mean glucose levels and HbA1c differs by race clearly needs to be determined and, if true, the magnitude of the difference and its clinical relevance should be determined. A study measuring glucose levels frequently enough to capture mean glucose levels with confidence, such as the ADAG Study, but including a large population from different races is necessary to address this issue satisfactorily. Until then, the current studies are neither scientifically valid nor compelling.
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