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. In a recent trial, the sensor-telemetry system functioned continuously while implanted in subcutaneous tissues of two pigs for a total of 222 days and 520 days respectively, with each animal in both non-diabetic and diabetic states. The sensor detects glucose via an enzyme electrode principle 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 two-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 minutes and 6.5 ± 13.3 minutes respectively, for rising and falling blood glucose challenges (mean ± SD). The lag was determined mainly by 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.

A patient-centered approach to device design can provide important advantages in optimizing diabetes care technology for broadened adoption and improved adherence. Results from two surveys of people with diabetes and the parents of children with diabetes ( = 1,348) regarding continuous glucose monitoring (CGM) devices reveal the importance of the concept of "user burden" in patients' and caregivers' evaluations of the acceptability of available devices. Survey respondents' strongly favorable reactions to a proposed 1-year, fully implanted CGM device with no skin-attached components further confirm that minimizing system obtrusiveness will likely be of significant value in reducing hurdles to CGM device use and adherence.

Objective The use of a fully implanted, first-generation prototype sensor/telemetry system is described for long-term monitoring of subcutaneous tissue glucose in a small cohort of people with diabetes. Methods Sensors are based on a membrane containing immobilized glucose oxidase and catalase coupled to oxygen electrodes and a telemetry system, integrated as an implant. The devices remained implanted for up to 180 days, with signals transmitted every 2 minutes to external receivers. Results The data include signal recordings from glucose clamps and spontaneous glucose excursions, matched respectively to reference blood glucose and finger-stick values. The sensor signals indicate dynamic tissue glucose, for which there is no independent standard, and a model describing the relationship between blood glucose and the signal is therefore included. The values of all model parameters have been estimated, including the permeability of adjacent tissues to glucose, and equated to conventional mass transfer parameters. As a group, the sensor calibration varied randomly at an average rate of −2.6%/week. Statistical correlation indicated strong association between the sensor signals and reference glucose values. Conclusions Continuous, long-term glucose monitoring in individuals with diabetes is feasible with this system. Significance All therapies for diabetes are based on glucose control and therefore require glucose monitoring. This fully implanted, long-term sensor/telemetry system may facilitate a new era of management of the disease.

Certain types of implanted medical devices depend on oxygen supplied from surrounding tissues for their function. However, there is a concern that the tissue associated with the foreign body response to implants may become impermeable to oxygen over the long term and render the implant nonfunctional. We report oxygen flux recordings from electrochemical oxygen sensor devices with wireless telemetry implanted in subcutaneous porcine tissues. The devices remained implanted for up to 13 weeks and were removed with adjacent tissues at specified times for histologic examination. There are four main observations: (1) In the first few weeks after implantation, the oxygen flux to the sensors, or current density, declined to a sustained mean value, having unsynchronized cyclic variations around the mean; (2) The oxygen mass transfer resistance of the sensor membrane was negligible compared to that of the tissue, allowing for a sensitive estimate of the tissue permeability; (3) The effective diffusion coefficient of oxygen in tissues was found to be approximately one order of magnitude lower than in water; and (4) Quantitative histologic analysis of the tissues showed a mild foreign body response to the PDMS sensor membrane material, with capillaries positioned close to the implant surface. Continuous recordings of oxygen flux indicate that the tissue permeability changes predictably with time, and suggest that oxygen delivery can be sustained over the long term.

Aim: To generate pilot data regarding acceptance, safety, and function of a novel long-term CGM. Methods: The investigational CGM (Eclipse 3, GlySens, San Diego, CA) was surgically inserted superficial to the rectus sheath in 8 type 1 diabetes adults (4 Female; Mean [SD] age 56 [7]; BMI 25 [3]). CGM data were masked to participants and processed retrospectively in simulated real-time with one capillary blood glucose calibration per day. Monthly visits evaluated: user acceptance by standardised questionnaire; health of implantation sites; safety by anti-glucose oxidase and anti-catalase antibodies; and performance benchmarked against YSI during standardised meal tests. Bluetooth communication between the sensor and an Apple iPhone was assessed continuously. Results: One sensor was removed at 4 months (participant withdrawal) due to impacted implant environment. There were no SAE’s. User acceptance remained high for the study duration. (Figure 1) Antibody levels did not rise. The lag corrected (23.3minutes) MARD (Median [range]) of 12.4% (1401 paired readings) was stable from month 1 (13.1%) to month 10 (14.0%). CGM readings within 20/20% and 30/30% of YSI values were 85% and 96%, respectively. The App received 95% of sensor data within 10 minutes. Conclusions: Our results provide initial data supporting participant acceptance, and safety of Eclipse 3. Further sensor refinement will reduce lag and improve performance. Disclosure A.Butler: Employee; GlySens Incorporated. J.Tan: None. D.N.O'neal: None. L.Robinson: None. V.R.Obeyesekere: None. H.Jones: None. Y.W.Kong: None. C.Yuan: None. K.Bertsch: Employee; GlySens Inc. T.L.Routh: Employee; GlySens Incorporated. S.L.Martha: Employee; GlySens Incorporated.