HbA1c for the Diagnosis of Diabetes and Prediabetes: Is It Time for a Mid-Course Correction?

摘要

The use of HbA1c for diabetes diagnosis is based on the hypothesis that HbA1c is a true and consis- tent measure of mean blood glucose. The best published data describing the relationship were reported in the HbA tIc-derived average glucose study (19). HbA1c, aver- aged across four methods calibrated to the recently devel- oped International Federation of Clinical Chemists stan- dard, was analyzed by regression against mean blood glucose, measured by both blood glucose meter and continuous glucose monitoring calibrated against the HemoCue analyzer to improve continuous glucose mon- itoring accuracy. Even with all these efforts to minimize measurement variability, a close examination of the rela- tionship reveals substantial uncertainty in the HbA1c pre- dicted from mean glucose or vice versa. This may be dis- turbing to some, but is not surprising to us. Our view is that the vast proportion of the variance in the HbA1c- mean glucose relationship results from interindividual dif- ferences in the biological determinants of hemoglobin gly- cation. That variation also explains why there is likely to be a trade-off between sensitivity and specificity for a sim- ple HbAtc-based diagnostic cut-off compared with any fasting, 2 h post-glucose load or mean blood glucose de- termination. Greater precision may be possible if we can better define the biological determinants of hemoglobin glycation and use that understanding to adjust the cut- points based on demographic, anthropometric, or labo- ratory measurements. Such approaches are routinely used in clinical medicine, for example, in diagnostic scoring for rheumatoid arthritis or in multivariate risk assessment in osteoporosis.