On June 6 and 7, academic and industry researchers joined in San Jose, California, for a two-day Artificial Pancreas Symposium. The tone of the conference was to discuss technology capable of monitoring glucose and automatically delivering the correct amount of insulin for the control of blood glucose in people with diabetes.
The major advantage of sensors providing frequent glucose measurements is the ability to detect hypoglycemia and sound an alarm, well before the onset of symptoms. Even without closed-loop control of an insulin pump, sensors have the potential to revolutionize the treatment of diabetes by providing glucose measurements with sufficient frequency to direct the proper timing and dose of insulin in relation to meals and daily activities.
Jeffrey I. Joseph, director of the Artificial Pancreas Center, department of anesthesiology at Thomas Jefferson University in Philadelphia, Pennsylvania, opened the symposium with a brief historical review of artificial mechanical beta-cell research, dating back 35 years. Joseph highlighted the recent commitment from the National Institutes of Health for increased research and funding.
David Klonoff, MD, clinical professor of medicine at the University of California, San Francisco and editor of Diabetes Technology and Therapeutics, provided an overview of type 1, type 2 and gestational diabetes, and discussed the need for frequent glucose monitoring combined with controlled basal/bolus insulin pump therapy. Klonoff outlined the characteristics of an “ideal” artificial mechanical beta-cell, including the technical and clinical challenges that need to be overcome to provide safe and effective glucose control during exercise, meals and stress
Implantable Blood Glucose Sensor with a Six-month Lifespan
Rajiv Shah, MS, director of sensor engineering for Medical Research Group in Sylmar, California, gave an overview of his company’s blood glucose sensor implanted long-term within the large vein returning to the heart. The sensor contains dual-oxygen polarigraphic electrodes, an active glucose oxidase enzyme sensing electrode and thermistor. In tandem, Shah says these provide significant sensitivity for glucose in blood with insensitivity to oxygen and temperature. Extensive in-vitro, animal and human testing have demonstrated the accuracy, robustness and ease of recalibration required for human clinical use. Shah says a six-month lifespan is anticipated with minimally invasive surgical techniques developed to inset a new sensor.
Sensor Uses Near-infrared Optics to Accurately Measure Glucose
Ian Shipway, senior project engineer for Animas Corporation of Fraser, Pennsylvania, provided a detailed description of Animas’s five-year implantable blood glucose sensor based on near-infrared spectroscopy. Short-term animal studies have demonstrated the ability of near-infrared optics to accurately measure glucose within the blood stream over a wide range of glucose and blood chemistry values. Shipway adds long-term studies in diabetic animals and initial human trials have been planned.
Adam Heller, PhD, professor of chemical engineering at the University of Texas in Austin, Texas, gave a detailed description of the chemical processes and protective membranes required for in-vivo blood and interstitial BG sensors. Heller highlighted the importance of the protective membrane and described the major causes of sensor failure, notably the chemical interference from heavy metals (zinc and iron) and the rapid fouling of protective membranes due to the deposition of protein and adhesion and inward migration of cells.
Disetronic Developing Non-enzymatic ISF Sensor
Bruno Reihl, PhD, director of research for Disetronic Medical Systems AG in Burdgorf, Switzerland, discussed how Disetronic is developing a non-enzymatic interstitial fluid (ISF) sensor based on changes in viscosity of a proprietary fluid when exposed to glucose. Dr. Reihl described a European collaboration for the development of a closed-loop technical pancreas system, with clinical testing in ambulatory type 1 diabetics anticipated for 2001.
Implanted Sensor Measures BG Over Three Days
John Mastrototaro, PhD, vice president of sensor development and manufacturing for MiniMed, provided an overview of MiniMed’s electrochemical ISF glucose monitoring system. The miniature needle-like sensor remains under the skin for three days with data recorded for subsequent physician interpretation. Mastrototaro says data currently being submitted to the U.S. Food and Drug Administration says the sensor will permit long-term monitoring with automatic alarms to warn of hypoglycemia and direct patient access to the real-time glucose. Clinical studies have demonstrated improved glucose control in patients with type 1 diabetes by more effectively distributing the insulin dose throughout the day, rather than increasing the total dose.
Non-invasive System Measures ISF in Real-time
Mark Faupel, PhD, vice-president for research and development at SpectRx in Norcross, Georgia, provided a detailed review of SpectRx’s non-invasive system for monitoring ISF in real-time. A laser is used to produce several micropores in the skin. Eight to 12 microliters per hour of ISF continuously flow into the external sensor’s collection reservoir. Glucose is measured every 15 minutes using a conventional electrochemical sensor.
GlucoWatch Provides Up to Three BG Measurements Per Hour
Tom Conn, PhD, vice-president of product development for Cygnus in Redwood City, California, provided an overview of Cygnus’s non-invasive glucose sensor, the GlucoWatch Biographer. The GlucoWatch uses an electric current to coax ISF from the subcutaneous tissue to a disposable GelPad worn beneath the watch. Electrons formed by a chemical reaction within the GelPad are measured using traditional amperometric techniques. Several hours of warm up are required following placement of the GelPad. A maximum of three glucose measurements is provided per hour, limiting the potential of this technology as a sensor for an artificial pancreas. ISF glucose measured with the GlucoWatch has been demonstrated to compare favorably, in a wide variety of clinical situations, with finger-stick glucose measurements.
Table-top Device Uses Infrared Light To Measure Glucose
Jim Braig, PhD, president of Optiscan Biomedical Corporation in Alameda, California, described a non-invasive, tabletop device that measures glucose under the skin using infrared light. Improved sensitivity for glucose is obtained by rapidly alternating skin temperature beneath the sensor head (30 to 40 degrees Celsius). Up to eight wavelengths of mid-infrared light interact with tissue fluid glucose before passing through optical filters to reach the sample glucose detector. The optical absorption spectra at discrete wavelengths are used to predict the actual glucose concentration.
Long-term Implantable Glucose Sensor and Pump System Approved in Europe
Ron Lebel, chief operating officer for Medical Research Group, then detailed the history of implantable insulin pump technology. The implantable insulin pump developed by the Johns Hopkins Applied Physics Lab and MiniMed has been licensed to and optimized by Medical Research Group. The improved pump has a 10-year anticipated battery life span, dual microprocessors, advanced software for programmability and safety, a smaller pump communicator and hermetic connectors for attachment to Medical Research Group’s long-term implantable glucose sensor. Insulin precipitation within the pump’s valves and catheter has been eliminated following the introduction of a newly formulated insulin by Aventis Pharmaceuticals. The integrated sensor and pump system has been implanted in diabetic animals and humans with encouraging results using open-loop and closed-loop algorithms for controlled insulin delivery into the peritoneal cavity.
Insulin Pump is First Step to Company’s Artificial Pancreas
Reihl then detailed Disetronic’s development of a permanent catheter system for delivery of insulin from an external infusion pump to the peritoneal cavity, providing physiological portal vein absorption. An inner catheter is replaced by the physician every few months to prevent obstruction due to insulin precipitation and tissue overgrowth. The risk of infection is minimized by the firm attachment of skin to the titanium housing. Peritoneal insulin delivery using an external pump in ambulatory patients with type 1 diabetes has provided excellent glucose control with few hardware problems. Disetronic plans to integrate an ISF glucose sensor, a closed or semi-closed computer control algorithm, and the insulin pump as their preferred artificial pancreas system.
John Walsh, PA, CDE, of The Diabetes Mall in San Diego, California, then described the components and requirements of an idealized artificial pancreas system. The advantages of peritoneal insulin delivery was highlighted, as well as how peritoneal catheters provide higher insulin levels to the liver during nutrient absorption and lower system insulin levels. The risk of ketoacidosis, hypoglycemia and infection raise the issue of device failure and fail-safe methods to prevent patient injury. Although beta-cell transplant was described as the greatest competitor to artificial pancreas technology, a reliable source of islet cells and long-term cell survival without immunosuppression are still lacking.
Only One Microliter of ISF Needed for Accurate Glucose Determination
Phil Stout, MS, senior scientist at Integ in Roseville, Minnesota, provided an overview of Integ’s Life Guide System, a hand-held glucometer that requires only a one-microliter sample of ISF for accurate glucose determination. ISF samples can be obtained from any region of the body with minimal discomfort. Glucose is determined using a standard enzyme calorimetric technique.
Meter Requires 0.3 Microliters of Blood
Ben Feldman, PhD, product development scientist for TheraSense in Alameda, California, described the FreeStyle meter, which requires only a 0.3 microliter sample of blood for accurate glucose determination. Blood samples can be obtained from any region of the body with minimal discomfort. The automated systems provide a fast response time (15 seconds) using a standard enzyme calorimetric technique.
TheraSense is also designing a minimally invasive continuous glucose-monitoring device. The device is designed to be easily inserted, contain a hypo- or hyperglycemia alarm and have a disposable sensor that lasts for several days.