Estimating Glycemia from HbA1c and CGM: Analysis of Accuracy and Sources of Discrepancy.

Objective. To examine the accuracy of different periods of continuous glucose monitoring (CGM), hemoglobin A1c (HbA1c), and their combination for estimating mean glycemia over 90 days (AG90). Research Design and Methods. We retrospectively studied 985 90-day CGM periods with <10% missing data from 315 adults (86% type 1 diabetes) with paired HbA1c measurements. The impact of mean red blood cell age as a proxy for non-glycemic effects on HbA1c was estimated using published theoretical models and compared with empirical data. Given the lack of a gold standard measurement for AG90, we applied correction methods to generate a reference (eAG90) that was used to assess accuracy of HbA1c and CGM. Results. Using 14 days of CGM at the end of the 90-day period resulted in a mean absolute error [95th percentile] of 14 [34] mg/dL compared with eAG90. Using two non-overlapping 14-day periods reduced the error to 6 [15] mg/dl. Non-glycemic effects on HbA1c led to a mean absolute error for average glucose calculated from HbA1c of 12 [29] mg/dL. Combining 14 days of CGM with HbA1c reduced the error to 10 [26] mg/dL. Mismatches between CGM and HbA1c greater than 40 mg/dL occurred more than 5% of the time. Conclusions. The accuracy of estimates of eAG90 from limited periods of CGM can be improved by averaging with HbA1c or extending the monitoring period beyond 26 days. Large mismatches between eAG90 estimated from CGM and HbA1c are not unusual and may persist due to stable non-glycemic factors.