HbA_1c Expressed as 'Estimated Average Glucose'

SAN FRANCISCO — Hemoglobin A_1c levels can now be accurately expressed as estimated average glucose for most patients with type 1 and type 2 diabetes.

In a multinational study presented at the annual scientific sessions of the American Diabetes Association, data from both continuous glucose monitoring and fingerstick monitoring over 3 months in 507 individuals with and without diabetes were compared with hemoglobin A_1c values to derive a formula that relates average glucose levels to HbA_1c.

The finding means that laboratories will now report both numbers (as well as the actual value in mmol/mol), and physicians can begin discussing glucose control with their patients in the same units that patients are familiar with from their home blood-glucose monitoring. “Right now, patients hear that their glucose control is some percentage, and are asked to adjust their therapy to achieve results in another unit. We thought it made sense to have both the day-to-day monitoring and the [HbA_1c] in the same units,” lead author Dr. David M. Nathan said at a press briefing during the meeting.

The shift to what is now being called the “estimated average glucose,” or “eAG,” began in 2002, when the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) published a new reference method that measures the concentration of only one molecular species of glycated hemoglobins (the A_1c), as opposed to the mixture that had previously been measured. Recognizing that the IFCC's adoption of the new reference method would cause confusion in the clinical setting, an international working group decided in 2004 to launch the study for which final results are now being reported. The study will also appear in the August issue of Diabetes Care (2008;31:1-6).

Although previous data had provided a rough estimate of average glucose from HbA_1c—and indeed, many labs have long reported those numbers—they were generated from old studies using infrequent fingerstick monitoring. In contrast, the participants in this study, who were recruited from 11 centers in the United States, Europe, Africa, and Asia, generated approximately 2,400 glucose measurements each by wearing the continuous glucose meter for at least 2 days at baseline and then every 4 weeks during the next 12 weeks, and another 300 values by performing eight fingerstick glucose measurements per day for at least 3 days per week. Hemoglobin A_1c values were measured at baseline and monthly for 3 months, Dr. Edward S. Horton, professor of medicine at Harvard Medical School, Boston, explained during the briefing.

Of the 507 analyzed study participants, 268 had type 1 diabetes, 159 had type 2, and 80 were not diabetic. Of the initial 661 patients recruited into the study, 18% had baseline hemoglobin A_1c values greater than 8.5%; 44% had values of 6.6%–8.5%; and 38% had values of 4.0%–6.5%. These levels generally remained stable with 96% of the subjects maintaining values within 1 percentage point of their baseline value.

At the end of 3 months, the relationship between the HbA_1c level and the calculated average glucose (AG) during the preceding 3 months could be expressed in the following formula: AG (in mg/dL) = 28.7 × HbA_1c - 46.7. That translates to an eAG of 97 mg/dL for an HbA_1c of 5%; 126 mg/dL for 6%; 154 mg/dL for 7%; 183 mg/dL for 8%; 212 mg/dL for 9%; 240 mg/dL for 10%; 269 mg/dL for 11%; and 298 mg/dL for 12%, Dr. Horton said.

For the overall study results to be considered acceptable, it had been decided a priori that at least 90% of the individual patients' calculated AG would have to fall within 15% of the studywide calculated AG. The actual percentage was 89.95%, and was considered to have met the requirement.

There was no effect of gender, age, ethnicity, diabetes type, or cigarette smoking on the results. However, the number of ethnic minority patients was small, which is a limitation of the study. Other limitations include the lack of data on children, pregnant women, or people with impaired renal function, Dr. Horton noted.

In the fall of 2007, a joint consensus statement from the American Diabetes Association (ADA), the European Association for the Study of Diabetes, the IFCC, and the International Diabetes Federation had called for labs to begin reporting HbA_1c in the familiar percentage, in the new eAG, and in the actual values in mmol/mol, pending the results of this study (Diabetes Care 2007;30:2399-400).

At the briefing, study coauthor Dr. Robert Heine, now with Eli Lilly & Co., noted that although lab reports will now contain three different numbers expressing the same value instead of two, the “whole idea behind the study is to simplify education in clinical practice. Now three numbers will be reported, but we really hope that just one number will be applied in clinical practice, and that's the eAG. … The advantage of having this eAG is that we can now educate our patients in a way that they can understand the relationship between long-term glycemic control and what they're doing at home, making it much easier for them to appreciate what blood glucose control means.”