Function of an Implanted Tissue Glucose Sensor for More than 1 Year in Animals

An implanted tissue glucose sensor can provide stable readings of glucose concentrations for more than a year. Sweet Sensor The need for an automatic, long-term implanted glucose sensor for use in diabetes therapy has been acknowledged by the diabetes care community for several decades. However, it was previously unclear that a sensor-telemetry system could be developed that functions long enough (1 year or more) to justify implantation of such a device, and that the implant could avoid encapsulation by tissues and rejection by the body. Gough et al. describe long-term studies in animals of a continuous, totally implanted glucose sensor that wirelessly transmits glucose concentration values to an external receiver. When available for use in humans, the implant will allow people with diabetes to monitor tissue glucose continuously and report via telemetry to an external receiver that displays the blood glucose information or relays it to a caregiver. Control of blood sugar, or blood glucose, is essential for normal daily activities. For people not having diabetes, blood glucose levels remain remarkably constant during the day, except for a brief modest rise after eating followed by a rapid return to a baseline. However, for people with diabetes, blood glucose levels can remain significantly elevated for long periods after eating and are only occasionally found at the ideal baseline. Further, for people who must inject insulin to bring blood glucose back toward baseline levels after eating, there is the real possibility of blood glucose levels becoming too low. High blood glucose is linked to a number of metabolic problems and can cause serious long-term consequences such as kidney disease, blindness, heart disease, and other problems that can reduce the quality of life, whereas blood glucose levels that are too low are immediately dangerous and can lead to temporary mental impairment, loss of consciousness, and accidents. All treatments for diabetes (insulin, oral medications, and potential new treatments in the research pipeline) are intended in some way to reestablish normal control of blood glucose. People with diabetes should measure their blood glucose concentration many times during the day. The sensor system described by Gough et al. provides an alternative to the most common means for measurement of blood glucose, which involves blood collection by “fingersticking” and glucose detection by placing a drop of blood in a handheld device. This method is inconvenient and only minimally acceptable to most people with diabetes, and is rarely performed frequently enough to follow rapid blood glucose changes. The new sensor system would also be an alternative to other forms of continuous glucose monitoring used by some people with diabetes, in which sensors are inserted into subcutaneous tissues by introducer needles and remain for 3 to 7 days before being replaced. Gough et al. reported on long-term glucose monitoring with the sensor-telemetry system implanted in subcutaneous tissues of pigs. Monitoring was carried out while the pigs were initially nondiabetic (for 3 weeks in one animal and nearly 1 year in the other) and, after the pigs had been made diabetic by administration of a laboratory drug, the monitoring continued in each animal for an additional 6 months, with diabetes being managed by frequent insulin injections and diet. These studies show that by proper design of the sensor system, previous reservations can be overcome. The long-term animal results reported by Gough et al. provide a foundation for human trials, which may require several years. An implantable sensor capable of long-term monitoring of tissue glucose concentrations by wireless telemetry has been developed for eventual application in people with diabetes. The sensor telemetry system functioned continuously while implanted in subcutaneous tissues of two pigs for a total of 222 and 520 days, respectively, with each animal in both nondiabetic and diabetic states. The sensor detects glucose via an enzyme electrode that is based on differential electrochemical oxygen detection, which reduces the sensitivity of the sensor to encapsulation by the body, variations in local microvascular perfusion, limited availability of tissue oxygen, and inactivation of the enzymes. After an initial 2-week stabilization period, the implanted sensors maintained stability of calibration for extended periods. The lag between blood and tissue glucose concentrations was 11.8 ± 5.7 and 6.5 ± 13.3 minutes (mean ± standard deviation), respectively, for rising and falling blood glucose challenges. The lag resulted mainly from glucose mass transfer in the tissues, rather than the intrinsic response of the sensor, and showed no systematic change over implant test periods. These results represent a milestone in the translation of the sensor system to human applications.