Feasibility of Continuous Long-Term Glucose Monitoring from a Subcutaneous Glucose Sensor in Humans

Abstract

The feasibility of continuous long-term glucose monitoring in humans has not yet been demonstrated. Enzyme-based electrochemical glucose sensors with telemetric output were subcutaneously implanted and evaluated in five human subjects with type I diabetes. Subject-worn radio-receiver data-loggers stored sensor outputs. Every 1-4 weeks the subject's glucose levels were manipulated through the full clinical range of interest using standard protocols. Reference blood glucose samples were obtained every 5-10 min and analyzed in our hospital clinical laboratory and/or on glucose meters. The sensor data were evaluated versus the reference data by linear least squares regression and by the Clarke Error Grid method. After surgical explantation and device inspection, the tissue-sensor interface was evaluated histologically. The remaining sensor-membranes were also recalibrated for comparison with preimplant performance. Four of the five glucose sensors tracked glucose in vivo. One sensor responded to manipulated glucose changes for 6.2 months with clinically useful performance (>/=90% of sensor glucose values within the A and B regions of the Clarke Error Grid). For this sensor, recalibration was required every 1-4 weeks. The other three transiently responding sensors had electronic problems associated with packaging failure. The remaining sensor never tracked glucose because of failure to form any sustained connection to adjacent subcutaneous tissue. Thus, stable, clinically useful sensor performance was demonstrated in one of five subjects with diabetes for a sustained interval of greater than 6 months. While this glucose sensor implant technology shows promise in humans, it needs to be made more reliable and robust with respect to device packaging and sensor-tissue connection.

A Wireless-Implantable Microsystem for Continuous Blood Glucose Monitoring

“…The early period of inconsistent monitoring can be as early as six days or be delayed two or three months for reasons that are not yet clear [14]; but it is believed that miniaturization of the implant can minimize this period because the implant is then less sensitive to the patient's movements [14].…”

“…viously presented implantable units have relatively large sizes primarily due to the construction of the implantable device using discrete electronic components assembled on medium-size circuit boards; and second, due to using a battery for powering the implant. The size of the implant plays a key role in the success of the monitoring system [14]. A smaller implant can be more easily packaged and be simply implanted via outpatient surgery.…”

“…It also provides more comfort for the patient and more options for the implantation site. However, the most important advantage of a smaller implant is that it promises a longer consistent in-vivo monitoring lifetime because a smaller implant is less sensitive to a patient's movement; thus, the tissue surrounding the implant comes to stability more rapidly and stays stable for a longer period of time [14]. A second problem of the previously published implantable units is that they have used conventional electrochemical glucose sensors (either oxygen-based or hydrogen peroxide-based sensors) for glucose sensing.…”

Biomechanics of the Sensor-Tissue Interface—Effects of Motion, Pressure, and Design on Sensor Performance and Foreign Body Response—Part II: Examples and Application

“…In a study by Gilligan and colleagues, 16 fully implantable sensors were surgically placed into the abdominal subcutis of humans. The authors reported that one of the five sensors never tracked glucose, and upon ex vivo examination, it was discovered that there was no tissue ingrowth into the sensor housing.…”

Neurochemical and Structural Organization of the Principal Nucleus of the Inferior Olive in the Human

“…They were then processed for immunohistochemistry as previously described. Immunoreactivity was visualized with a DAB protocol or the glucose oxidase modification of it (Adams, 1981;Gilligan et al, 2004;Van der Gucht et al, 2006).…”