Problem: Deadly Disease and Painful Care

Diabetes mellitus impairs the way the body uses digested food for energy. Diabetes is a chronic, life-threatening disease for which there is no known cure.

We estimate that there are currently more than 3 million Americans with severe diabetes who are insulin-dependent and must monitor their blood glucose levels an average of five times a day. Tightly managing blood glucose levels can dramatically decrease the risk of serious heart complications, blindness, kidney failure and death. Despite the serious consequences of poor blood glucose control, only 37% of patients with diabetes are achieving the level of control recommended by the American Diabetes Association.

Currently, the only reliable way to monitor glucose levels is to use inconvenient and painful test strip technology.  People draw blood by piercing their fingers (as shown in figure below) and placing a drop of blood on a strip with glucose oxidase (GOx), the enzyme used in glucose meters. While effective at reading blood glucose levels, test strips have considerable drawbacks including: Pain – Piercing the skin several times a day causes discomfort. Inconvenience – Blood is drawn generally before meal times, forcing people with diabetes to find a discrete place to test their blood. Discontinuous results – Periodic test strip results do not show real-time and continuous glucose level trends.

 

Continuous Glucose Monitors

Continuous glucose monitors (CGMs) offer an alternative to the test strip method.  This technology does not require drawing blood from fingers.  Instead, a sensor is placed just under the skin every three to seven days, sending continuous readings to a small, pager-sized device (as shown in figure below).

  CGMs offer people with diabetes the following benefits above test strips:

• No blood withdrawal – Elimination of finger pricks to decrease pain and discomfort.
• Continuous results – Trend analysis allows patients to see both historical and real-time alerts.
• Alerts to swings in glucose levels – Alarm systems are built in to alert patients when glucose levels are reaching extreme upper or lower limits before triggering more serious health problems.
• Integration with the insulin pump – Some CGMs are designed for use with the insulin pump, which continuously injects insulin into the bloodstream for true hands-off diabetic care.

 

Pain in the Market

Despite the many advantages, CGMs cannot be used as a replacement for finger stick devices primarily due to poor accuracy and high cost. The low accuracy, with average measurement discrepancy results greater than 20%, means that patients cannot be sure of their actual glucose level.  Because of this low accuracy, CGMs have not been FDA approved for stand-alone use.  Instead, test strips must still be used to calibrate and confirm measurement, which erode their true value as bloodless devices. 

Greater accuracy is also a selling point for CGMs to be covered by major health insurance companies. Because of the very limited insurance coverage, the annual cost of CGMs is more than ten times that of test strips to the end users. 

Being the next standard in diabetic health care hinges on increasing the accuracy of CGMs. Armored Enzyme Technology addresses these concerns by making CGM sensor measurements more accurate.  Most glucose sensors depend on the activity of the enzyme glucose oxidase (GOx) to break down glucose into smaller elements (hydrogen peroxide) that will be further transformed into electron signals.  The signals are then interpreted as the glucose reading.  The more glucose there is in the sample, the more peroxide the GOx creates, and the stronger the signal, which indicates the blood glucose level at the electrode.

CGMs, on the other hand, operate in the interstitial compartment where they face challenges in terms of sensitivity, stability, calibration, and the physiological time lag between blood and interstitial glucose concentration. CGM sensors are also sensitive to non-glucose related environmental changes in the baseline current and sensitivity over time, for example, due to changes in a host's metabolism, maturation of the tissue at the biointerface of the sensor, interfering species which cause a measurable increase or decrease in the signal. Therefore, in addition to initial calibration, CGM sensors must be responsive to baseline and/or sensitivity changes over time, which requires recalibration of the sensor.

Replacing normal GOx with Armored GOx increases enzyme density, stability and activity in the sensors.  The enzyme can then break down more glucose and yield more accurate test results than normal immobilized GOx in the sensor.  This superior accuracy can also make the hyper/hypoglycemic alarm much more reliable by reducing the number of false alarms.  

By solving the accuracy problem of CGMs, Armozyme technology will allow CGMs to be stand-alone FDA cleared devices without the need for calibration, inducing greater demand for the whole industry.