Data Suggest HbA_1c Can't Be Switched to Mean Blood Glucose

Attempts to translate hemoglobin A_1c into mean blood glucose via a mathematical formula are likely to introduce substantial error, according to data from an analysis of continuous glucose monitoring data in 47 children with type 1 diabetes.

A recent multinational trial identified a formula for converting HbA_1c to mean blood glucose, based on continuous glucose monitoring (CGM) data from 643 diabetic and nondiabetic subjects. Pending the final results of that study, the American Diabetes Association, the European Association for the Study of Diabetes, the International Federation of Clinical Chemistry and Laboratory Medicine, and the International Diabetes Federation have called for laboratories to report that mean glucose value in addition to the HbA_1c itself (Diabetes Care 2007;30:2399–400).

However, new data from the Diabetes Research in Children Network (DirectNet) Study Group suggest that although HbA_1c does clearly reflect mean glucose, there is substantial variability in individual mean glucose concentrations for a given HbA_1c value. Moreover, the strong relationship between HbA_1c and the risk for diabetic complications may reflect not only mean blood glucose but also a patient's propensity to glycosylate other structural proteins, said Dr. H. Peter Chase of the University of Colorado, Denver, and colleagues (Diabetes Care 2008;31:381–5).

The 47 patients, aged 4–18 years, included 28 pump users and 19 who took multiple daily injections using glargine as their basal insulin. They wore Abbott Laboratory's FreeStyle Navigator continuous glucose monitor for an average of 115 hr/wk. The slope of mean glucose over the previous 3 months was 18 mg/dL per 1.0% HbA_1c, with considerable variation in glucose concentrations for any given HbA_1c. This relationship was similar between the pump users and those taking injections, and at both 3-month and 6-month visits.

“For any given A_1c level, mean sensor glucose levels differed by up to 50 mg/dL or more, making the conversion of A_1c into mean glucose equivalents as suggested by a recent American Diabetes Association consensus statement tenuous at best,” the study group commented.

Two measures of a patient's rate of glycation—a simple ratio of mean glucose to HbA_1c and a derived “glycation index”—remained relatively constant over the 6 months of the study, suggesting that individuals glycate proteins at different rates and the tendency to be a fast or slow “glycator” persists over time.

After controlling for mean glucose over the previous 3 months, HbA_1c was not significantly associated with measures of glucose lability, thus refuting findings in other studies that high glucose values contribute disproportionately to the HbA_1c value. “We found no evidence to contradict the simple hypothesis that A_1c directly reflects the integral of glucose level over time,” they said.

The group cautioned that because children and adolescents may have higher glycemic variability than do adults, the findings may not be directly applicable to adult patients.

Funding for the study was provided by the National Institutes of Health; Abbott Diabetes Care provided the continuous glucose monitors and test strips.