People with diabetes have traditionally measured their glucose levels using blood glucose meters. This tried and tested technology has been around since the 1960’s with many developments that have improved accuracy, reduced test times and reduced the required blood volumes. With the introduction of continuous glucose monitors at the turn of the century, a new sample medium for glucose testing was introduced in the form of interstitial fluid - commonly referred to by the abbreviation ISF. Continuously measuring glucose in whole blood is not practical for the home user, whereas a range of glucose monitoring systems have been developed to conveniently and continuously measure glucose in the ISF due to the ease of use and safe accessibility.
Interstitial fluid, or ISF, is simply the intracellular fluid that surrounds the cells and feeds them nutrients including glucose (Figure 1). Glucose sensor systems measure glucose in the ISF by inserting a glucose sensing filament into the subcutaneous tissue which sits just below the dermis (top layer) of the skin. This subcutaneous tissue comprises of ISF which contains glucose transported from blood capillaries. The glucose levels in the ISF closely follow blood glucose, albeit with a slight time delay. The delay has been estimated at between 5 and 10 minutes in various studies, and is therefore unlikely to impact routine day-to-day treatment decisions. The delay can be more noticeable when a person’s glucose is changing rapidly, for example after a high glycaemic index meal or during exercise. To compensate for this, devices which measure glucose in the ISF employ complex algorithms which can compensate for rapidly changing glucose levels, resulting in accurate glucose measurements for the end user. Trend arrows also indicate the rate and direction of the glucose change to the user.
Figure 1 – Glucose Sensor measuring glucose in the interstitial fluid
The FreeStyle Libre flash glucose monitoring system uses a sensor filament which is inserted 5 millimetres under the skin and accurately measures glucose in the ISF5. The FreeStyle Libre sensors are calibrated at the factory. The factory calibration is designed to give sensor glucose results which are more comparable to blood glucose results. However, your sensor interstitial fluid result may not always be the same as a blood glucose result obtained at a similar time. Differences in glucose readings between interstitial fluid and capillary blood may be observed during times of rapid change in blood glucose, such as after eating, dosing insulin or exercising. Severe dehydration and excessive water loss may also cause inaccurate results*.
Different results may be similarly observed when comparing blood glucose results from different blood glucose meters. For example, if a person’s blood glucose is actually 7 mmol/L, their blood glucose reading could be as low as 5.9 mmol/L on one meter and as high as 8.1 mmol/L on another, both would be considered accurate by the international standard for blood glucose meter accuracy.
 Clarke SF, Foster JR. A history of blood glucose meters and their role in self-monitoring of diabetes mellitus. British Journal of Biomedical Science 2012;69(2):83-94
 Rebrin K, Steil GM. Can interstitial glucose assessment replace blood glucose measurements? Diabetes Technology and Therapeutics 2000;2(3):461-472
 Cengiz E, Tamborlane WV. A tale of two compartments: Interstitial versus blood glucose monitoring. Diabetes Technology and Therapeutics 2009;11(S1):S11-S16
 Rebrin K, Sheppard NF, Steil GM. Use of subcutaneous interstitial fluid glucose to estimate blood glucose: Revisiting Delay and Sensor offset. Journal of Diabetes Science and Technology 2010;4(5):1087-1098
5 Bailey et al. The performance and usability of a factory-calibrated flash glucose monitoring system. Diabetes Technology and Therapeutics 2015;17(11)
* A finger prick test using a blood glucose meter is required during times of rapidly changing glucose levels when interstitial fluid glucose levels may not accurately reflect blood glucose levels, or if hypoglycemia or impending hypoglycemia is reported or the symptoms do not match the system readings. If you believe you are suffering from dehydration, consult your health care professional immediately.