Public Release: 

On the horizon of glucose monitoring: A review

Penn State

Doctors recommend that diabetics who take insulin check their blood glucose levels four times a day. But piercing a nerve-rich fingertip and squeezing out a drop of blood onto a test strip is painful, and often deters people from checking any more than just once. Frequent testing allows insulin-dependent diabetics to tightly control their blood glucose levels and gives them the best chance of preventing major complications of diabetes, such as vision loss from retinopathy, non-traumatic amputations or kidney disease.

"Non invasive, or even less invasive, options for monitoring blood glucose would likely result in better compliance with our four-times-a-day testing recommendation," said Robert Gabbay, M.D., Ph.D., director of the diabetes program and associate professor, Penn State College of Medicine. "Better monitoring means patients could keep their blood glucose at the levels necessary to ward off complications."

Gabbay conducted a review of new developments in glucose monitoring technology both for patient comfort and for their potential to improve patient outcomes. The article appeared in the Sept. 15 issue of Canadian Journal of Diabetes.

Diabetes is a disease in which the body doesn't make enough insulin, or isn't able to appropriately use the insulin produced by the body. Insulin is a hormone made by the pancreas to regulate the amount of sugar in the blood. High levels of glucose in the blood can seriously affect other body systems, particularly over time. The most common and, to date, the most inexpensive way to monitor blood glucose is by piercing the finger with a small needle and squeezing a drop of blood onto a test strip. The test strip is fixed to a small monitor, which measures the blood glucose.

For this review, Gabbay divided the newest monitoring technologies into three categories: noncontinuous and minimally invasive; continuous but invasive; and continuous and noninvasive.

Noncontinuous and minimally invasive: Several companies have developed products that are less invasive and require smaller blood volumes. With these products, blood can be drawn from other areas of the body such as the arms and legs.

"However, blood drawn from a site other than the finger appears to more slowly reflect the changes in blood sugar, meaning a sample from the finger might detect elevated blood glucose levels earlier than a sample from an alternate site," Gabbay said. "And although less painful than the nerve-rich fingertips, these products still require piercing the skin."

Other minimally-invasive techniques use interstitial fluid, or the fluid between cells, and only require that the uppermost layer of dead skin be breached. However, interstitial glucose levels may not always match blood glucose levels because of a lag in transport of glucose from the capillaries to the interstitial space. Temperature and perspiration can also affect fluids in the interstitial space and influence the measurements.

Continuous but invasive glucose monitoring: Continuous glucose monitoring can have significant advantages. For example, the management of a glucose value of 150 mg/dL (target is about 80-120 mg/dL) during a rapid decline in glucose would be much different than management of the same level during a rapid increase.

"Currently, no information about direction of changes in glucose levels is available from periodic testing," Gabbay said. "Continuous glucose monitoring could uncover hidden glucose trends such as unrecognized glucose variations. With continuous monitoring, alarms could notify a person when blood glucose gets too high or low."

Current continuous, invasive glucose monitoring systems may use a needle sensor system, a micropore system, or a microdialysis system. The needle sensor system involves placing a needle under the skin, which sends data through a wire running through the skin to a monitor worn by the patient. Due to the possibility of swelling around the needle, these devices require frequent calibration via fingerstick tests at least three times a day. Also, no glucose readout is available to the patient so on-the-spot corrections in insulin can't be made. The data is stored and downloaded by a healthcare provider.

"Despite these limitations, physicians who have asked patients to wear this device have uncovered unrecognized glucose trends," Gabbay said. "This has allowed for better glucose control."

Micropore systems use a laser porator to put tiny holes in the uppermost layer of the skin, through which interstitial glucose is measured using a patch. Fingerstick calibration is required once a day. A sensor makes calibration adjustments for changes in temperature and glucose values appear to be accurate for 48 to 72 hours. Pediatric studies of a micropore system are underway.

Microdialysis can be used for subcutaneous, or under-the-skin, continuous glucose monitoring. For this method, a pump circulates a liquid through a tube into which interstitial glucose diffuses. A glucose sensor takes measurements and displays values every minute over a three-day period. This method, which is still under investigation, requires only one fingerstick every 72 hours for calibration. Continuous and noninvasive glucose monitoring: "Patient preference clearly points toward a completely noninvasive method for glucose monitoring," Gabbay said.

He says three promising approaches to noninvasive monitoring exist: iontophoresis, infrared spectroscopy and sonophoresis. Iontophoresis uses electric current to introduce ions into the body. This technology uses reverse iontophoresis to extract interstitial glucose for measurement within a watch-like device. The watch generates a small electrical field that attracts sodium ions along with water and glucose across the uppermost layer of the skin. This device requires a single fingerstick for calibration and measures glucose every three hours. An alarm to signals a person when blood glucose levels have strayed from normal ranges. An FDA-approved device of this kind is available in the U.S.

"This device is limited by skipping about 10 percent of readings, a significant price tag and some local skin irritation after its use," Gabbay said.

Near-infrared spectroscopy uses an external source with a wavelength that is just above that of the visible spectrum. The light passes through or is reflected by a body part. Light absorbed at selected wavelengths is then analyzed for each blood glucose level and an algorithm is used to develop a calibration curve. Frequent calibration is required to compensate for any changes in tissue hydration, body temperature, and hemoglobin level and for medications that might absorb infrared light.

"This method can establish trends but is not reliable enough to determine day-to-day changes in insulin administration," Gabbay said. Sonophoresis uses low frequency ultrasound to cause temporary cavities in the uppermost layer of the skin. This causes aqueous channels to form through which small molecules, such as glucose, can diffuse. More studies will determine the effect of repeated ultrasound application to human skin.

"In conclusion, several promising approaches are currently under investigation to make glucose monitoring more patient friendly and to improve clinical outcomes," Gabbay said. "Each method has its benefits and drawbacks. But regardless of technology, its vitally important for diabetics to keep a good handle on blood glucose levels."

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