Calibration process

Proper calibration is the basis for the continuous glucose monitoring system accuracy and reliability. The calibration means setting a value of the calibration factor or in other words setting the relation between ISIG and interstitial fluid glucose values according to formula {Principles 2}. As there is no direct method to measure glucose values in the interstitial fluid, the calibration factor is determined by blood glucose reading obtained from meter under the presumption that interstitial fluid glucose values are equal to blood glucose values 10 minutes ago.

The Medtronic’s system working with Paradigm 522 and 722 insulin pumps requires input of blood glucose reading (calibration):

The calibration algorithm is based on measurement of ISIG values during the period of 10 minutes starting from glucose reading entry through the pump display. Collected ISIG values are smoothened and ISIG corresponding to the time 10 minutes after the blood glucose reading entry is related to the blood glucose reading according to formula {Principles 2}. The new calibration factor is available in 10 – 15 minutes plus display delay described in section "Sensor instrumental delay". The sequence of events in the calibration process is shown on Fig. Calibration 1.

Fig. Calibration 1.    Sequence of calibration process events

Case:
a)   the blood glucose reading is entered just before the interstitial glucose value is calculated and displayed. It takes 10 minutes (plus the display delay) since the blood glucose reading is entered till the interstitial glucose value using the new calibration factor is displayed. This is the shortest interval.
b)   the glucose reading is entered just after the interstitial glucose value is calculated and displayed. It takes 15 minutes (plus the display delay) since the blood glucose reading is entered till the interstitial glucose value using the new calibration factor is displayed. This is the longest interval.

My regression analysis shows that calibration factor values used by the pump differ from values calculated according to formula {Principles 2}. This happens in all cases except the first calibration after the sensor start (using menu options Sensor / Sensor Start / New Sensor or Sensor / Sensor Start / Reconnect Old Sensor). The calibration factor values used by the pump are in addition averaged with the previous value of the calibration factor according to formula
       CAL* = (CALPREV + CAL) / 2      {Calibration 1}
where CAL* is the calibration factor used by the pump,
CALPREV is the value of previous calibration factor
and CAL is the value of actual calibration factor calculated based on formula {Principles 2}.

An example of the calibration factor averaging is shown on Fig. Calibration 2.

Fig. Calibration 2.    Calibration factor averaging

The figure shows change of interstitial glucose values after the calibration. The blood glucose reading value 79 mg/dl was entered at 7:15. Interstitial glucose values till 7:22 were calculated using the old calibration factor value, while the new calibration factor value was used since 7:27 onwards. ISIG values during the calibration process were nearly constant varying between 12.30 and 12.64 nA. If there could not be any calibration factor averaging, the interstitial glucose value at 7:27 would be 79 mg/dl approximately, while it was 112 mg/dl in the reality.

The calibration factor averaging is an empiric method to make the system as stable as possible. It is used to reduce influence of interstitial fluid circulation variance, blood glucose readings dispersion described in section "Meter precision" and effects of low and high glucose values used for calibration described in section "Blood and interstitial fluid glucose profiles". On the other hand it leads to incorrect interstitial glucose values in cases when:

If any of these cases happens, re-starting the sensor is the only way how to obtain non-averaged calibration factor. I prefer to do it using menu option Sensor / Sensor Start / Reconnect Old Sensor as it keeps information about the sensor age.

The requirement of maximum 12 hours between subsequent calibrations is too strict. It has very logical background trying to spot changes in the value of calibration factor as soon as possible. But it is rather contra productive in the real life. Because the calibration factor value is influenced by following factors at the time of calibration:

it would be better to extend this interval for couple of hours. To get the reliable value of the calibration factor and predictive behavior of the continuous glucose monitoring system, it is important to measure the blood glucose values at times when they are stable and in the normoglycemic range. This is in my case difficult to achieve between breakfast and 4 hours after the last bolus or food of the day (afternoon snack or early dinner). The distance between these two points of time is 14 - 16 hours. As well it is quite difficult or even impossible to measure blood glucose values by the meter in case of the all-day long outdoor activities when outside temperature is below zero.

In case I need to extend the period of 12 hours by some time without measuring the blood, I use following formula to estimate the blood glucose value to be entered
       BG = 2 x SGACTUAL - SG-10 MINUTES       {Calibration 2}
where BG is the blood glucose value used for calibration,
SGACTUAL is the last (actual) interstitial glucose value displayed by the pump
and SG-10 MINUTES is interstitial glucose value at the time of 10 minutes before.
And of course, I restart the sensor using menu option Sensor / Sensor Start / Reconnect Old Sensor as soon as I reach conditions acceptable for reliable calibration. Restarting the sensor eliminates influence of possibly inaccurate blood glucose value used for this fake calibration.

Because the lag between my blood and interstitial glucose profiles is 12 minutes approximately, while Medtronic algorithm considers only 10 minutes, I usually wait 2 minutes before I enter blood glucose reading received from meter into my pump.