How the sensor measures glucose in the interstitial fluid

Interstitial fluid is the fluid that fills the spaces between the cells of your body, outside the blood vessels and outside the cells. It constantly surrounds the cells in the tissues and links the blood with the cells [1]. Through it, each cell receives glucose, oxygen and other substances needed for survival or proper functioning. This is also how the cells remove the products they no longer use (waste).

This fluid comes from plasma, the liquid part of the blood, and it passes through the thin walls of the body's smallest vessels, called capillaries. Interstitial fluid is found in abundance just under the skin, in the subcutaneous tissue, exactly where the thin filament of the sensor is placed. For this reason the sensor reaches it easily and can measure the glucose concentration there, without entering a blood vessel [2].

The sensor measures the glucose concentration in the interstitial fluid because this fluid is found just under the skin and can be reached easily with a very thin filament. Placing the filament in the subcutaneous tissue is simple and almost painless, and it stays there for several days, sometimes weeks [3].

Direct and continuous measurement in blood would require the sensor to sit permanently in a blood vessel. That would bring risks of infection, clot formation and injury to the vessel. Interstitial fluid offers a much safer and more convenient solution, and the glucose concentration in it closely follows the value in blood [4]. You can thus obtain repeated measurements at any time, without pricking your finger every time.

Glucose circulates through the blood and thus reaches the capillaries, which have very thin walls. From here, glucose passes through the capillary wall into the interstitial fluid. It moves from the place where it is present in a larger amount (the blood) towards the place where it is present in a smaller amount (the interstitial fluid). This passage is called diffusion and happens on its own (passively), without consuming energy [1].

After it reaches the interstitial fluid, glucose is taken up by the cells, some of them with the help of insulin, and others through their own transporters in the cell wall, which do not need insulin. In short, glucose's path is blood, the capillary wall, the interstitial fluid and finally the inside of the cell. The sensor is placed exactly on this route, in the fluid between the cells, and that is why it can track the glucose level almost in real time [2].

When blood glucose is stable, the glucose concentration in the interstitial fluid is closely correlated with that in plasma, although it is usually slightly lower, because the cells consume glucose continuously. In this situation, the value displayed by the sensor may coincide with blood glucose, not because the two concentrations are identical, but because the interstitial signal is calibrated against blood glucose (at the factory or by the patient). The difference appears when blood glucose changes quickly, for example after a meal, during exercise or after correcting a low value. At these moments, glucose needs a few minutes to pass from the blood into the interstitial fluid, so the sensor shows the value with a small delay [5].

For this reason, when blood glucose rises rapidly, the value in the interstitial fluid is slightly lower compared with that in blood. Conversely, when blood glucose falls rapidly, the value displayed by the sensor (from the interstitial fluid) is slightly higher compared with that in blood. These differences are generally reasonable and short-lived. Modern sensors even try to correct them through internal calculations, so that the displayed figure is as close as possible to the real blood glucose, as the figure below shows [6].

Yes, in most situations measurement in the interstitial fluid correctly reflects the blood glucose level, especially when the values are stable. The link between glucose in the interstitial fluid and that in the blood is close, and the sensor is designed to estimate blood glucose starting from this link. For everyday life, the information provided by the sensor is accurate enough to guide your decisions [4].

There are, however, a few situations in which the values may be less accurate. These include the first hours after fitting the sensor, rapid changes in blood glucose and the moments when certain substances interfere with the measurement [7]. That is why, if your symptoms do not match the figure on the screen, it is a good idea to measure your blood glucose with a glucometer [4]. Do the same immediately after you have corrected a low value. This simple check increases your confidence and safety in general, though it matters most before driving, before exercise, in pregnancy and on sick days.

The sensor measures the glucose concentration, that is the ratio between glucose and the surrounding fluid, not the total amount of glucose or fluid. For this reason, a small variation in the amount of interstitial fluid does not directly change the displayed value. What matters is how much glucose is found in a given volume of fluid, and this ratio remains close to that in the blood [6]. Nevertheless, the local conditions around the sensor can temporarily affect the measurement. Pressing on the sensor during sleep, dehydration, cold, local swelling or the tissue's normal reaction in the first hours after placement can alter the figures for a short time.

If you accidentally press on the sensor while you sleep, you will notice an unexpectedly low value, sometimes close to zero. This is an error known as nocturnal signal attenuation (NSA), and changing your sleeping position usually corrects it [8]. Before you put such a value down to this error, check your blood glucose with a glucometer, because a low reading can also be a genuine hypoglycemia.

All medical-use sensors and most non-medical-use ones measure the glucose concentration in the interstitial fluid [3]. This includes both transcutaneous sensors (with a thin filament placed just under the skin) and implantable sensors [7] [9]. All these devices use the same principle, of reading the glucose concentration in the fluid between the cells and then estimating blood glucose from it.

There is also research into sensors that would read glucose through the skin, without a filament, or directly from blood. The filament-free version uses near-infrared spectroscopy: it sends invisible light through the skin and analyzes how much of it comes back. These sensors are not yet part of the devices used daily to guide treatment [10]. In short, if you wear an ordinary sensor on your arm or abdomen, it measures glucose in the interstitial fluid.