A previous inpatient investigation from our group in 90 children with T1DM demonstrated that the median RAD of the original CGMS sensor was 19%6
. The percent of values meeting ISO criteria for the original sensor was only 53% overall and 41% for reference values≤70 mg/dL. The new CGMS Gold system was introduced in 2002, and our results confirm that the accuracy of this system is significantly improved when compared to the original version, particularly for values at or below 70 mg/dL6, 7
The primary aim of this study was to determine whether different calibration schemes could be utilized to improve further CGMS accuracy. Our results showed a slight improvement in sensor accuracy when additional calibration values are added with the median RAD improving from 14–15% with 3 or 4 calibrations each day, to 13% with 5 or 7 calibrations each day. Additional calibration values also tended to improve sensor performance during exercise in our subjects. In calibrating an implanted glucose sensor, Choleau, et.al8
assessed the benefit of using 1, 2, or 3 discrete one-point calibrations retrospectively each day. In their studies, increasing the number of calibration points from 1 to 2 to 3 also caused a slight improvement in the percent of values observed in Clark Error Grid zones A+B (84.8%, 88.1%, and 89.4%, respectively).
If the output from the subcutaneous sensor was always linearly related to the blood glucose and there was no change in the sensitivity of the sensor to glucose, a single calibration point would be sufficient. This assumes there is a direct relationship of the interstitial glucose to the blood glucose which does not vary with changing glucose concentrations. In actuality the interstitial glucose concentrations lag changes in the serum glucose by 4 to 10 minutes 8, 9
, and therefore when glucose levels are changing rapidly this physiologic lag in interstitial glucose levels could result in a less accurate calibration. This relationship (interstitial to blood glucose) becomes more divergent at lower blood glucose levels 10
. In contrast, when glucose levels are stable and there is equilibration between the interstitial and serum glucose levels, this error should be reduced. Our results confirm that sensor accuracy is decreased when blood glucose levels are changing rapidly. The median RAD using 4 calibration points was 13% when the rate of change was <0.5 mg/dL/min, but when the rate of change increased to ≥1.5 mg/dL/min the median RAD increased to 19%, and values meeting ISO criteria decreased from 69% to 58%.
The CGMS uses a retrospective calibration algorithm, but these results also apply to sensors that give glucose values in “real-time”. Our data support the wisdom of not allowing a calibration value to be entered into a real-time sensor if the glucose is changing by more than 2 mg/dL/min; a paradigm currently being employed in the Freestyle Navigator™ Continuous Glucose Monitor (Abbott Diabetes Care, Alameda, CA)11
Accuracy was not affected by using calibration values obtained either pre-prandially or about 2 hours post-prandially. Therefore blood tests to calibrate a sensor can be done when it is convenient for the patient, either pre-prandially or post-prandially, as long as the glucose values are obtained when there is not a rapid rate of change in glucose levels.
In past studies we have observed a consistent bias for the CGMS to read lower at night, and this was also observed by McGowan et. al.1
. A similar bias towards lower CGMS readings overnight was also observed in the present study. Using 4 calibration values the median bias during the day was +4 mg/dL, and overnight the bias was −9 mg/dL. This was not the result of more calibration values being obtained during the day than at night, because when we increase the number of nighttime calibration values, (including midnight and 3 a.m. calibration values so that 4 values were obtained bracketing and including the night) the daytime bias remained positive at +11 mg/dL and the nighttime bias remained negative at −8 mg/dL (). When we limited calibration values to those only obtained overnight, this bias was resolved (−2 mg/dL), but when we added back daytime calibration values the negative nighttime bias (−9 mg/dL) is again present. This would suggest the sensor output is higher during the day than overnight, the etiology for this bias was not assessed in this study. There could be a physiologic difference in the subcutaneous blood glucose, oxygen or blood flow overnight resulting in lower subcutaneous glucose measurements, or it is possible that decreased activity at night allows for nocturnal sensor “biofouling”. A separate calibration algorithm for overnight readings might therefore improve accuracy.
In summary, there is little improvement in sensor accuracy by including more than 4 calibrations each day, and only a slight improvement when increasing from 3 to 4 calibrations each day. Sensor accuracy was not significantly affected by obtaining glucose values preprandially or about 2 hours postprandially. Sensor accuracy was most improved by obtaining calibration values when there was not a rapid rate of glucose change. There is a bias for the sensor to read lower at night, and removing daytime calibration values improves overnight sensor accuracy. Modifying the algorithm to put less weight on daytime calibrations for nighttime values and calibrating during times of relative glucose stability may have the greatest impact on optimizing the use of calibration values.