Harvey B. Buck

Use of Microdialysis-Based Continuous Glucose Monitoring to Drive Real-Time Semi-Closed-Loop Insulin Infusion

Background: Continuous glucose monitoring (CGM) and automated insulin delivery may make diabetes management substantially easier, if the quality of the resulting therapy remains adequate. In this study, a semi-closed-loop control algorithm was used to drive insulin therapy and its quality was compared to that of subject-directed therapy. Method: Twelve subjects stayed at the study site for approximately 70 hours and were provided with the investigational Automated Pancreas System Test Stand (APS-TS), which was used to calculate insulin dosage recommendations automatically. These recommendations were based on microdialysis CGM values and common diabetes therapy parameters. For the first half of their stay, the subjects directed their diabetes therapy themselves, whereas for the second half, the insulin recommendations were delivered by the APS-TS (so-called algorithm-driven therapy). Results: During subject-directed therapy, the mean glucose was 114 mg/dl compared to 125 mg/dl during algorithm-driven therapy. Time in target (90 to 150 mg/dl) was approximately 46% during subject-directed therapy and approximately 58% during algorithm-driven therapy. When subjects directed their therapy, approximately 2 times more hypoglycemia interventions (oral administration of carbohydrates) were required than during algorithm-driven therapy. No hyperglycemia interventions (delivery of addition insulin) were necessary during subject-directed therapy, while during algorithm-driven therapy, 2 hyperglycemia interventions were necessary. Conclusions: The APS-TS was able to adequately control glucose concentrations in the subjects. Time in target was at least comparable or moderately higher during closed-loop control and markedly fewer hypoglycemia interventions were required, thus increasing patient safety.

Electrochemical Glucose Biosensors for Diabetes Care

Blood glucose monitoring (BGM) is the most successful application of electrochemical biosensor technology and has motivated tremendous improvements in biology, chemistry, measurement, and fabrication methods of biosensors. The performance of electrochemical biosensors used for BGM has improved greatly over the last four decades. Technological advance has allowed to measure blood glucose (BG) over a wide range of glucose concentration, a wide temperature and hematocrit range in the presence of an abundance of interfering substances with ever-increasing accuracy, and precision in minute sample volumes. The use of optimized enzymes, mediators, and electrochemical measurement methods enables this tremendous progress in performance. Continuous glucose monitoring (CGM) systems based on minimally invasive amperometric sensors, inserted into the subcutaneous tissue, have significantly improved over initial offerings over the last 15 years with regard to time of use, accuracy, reliability, and convenience due to a multitude of parallel advances: materials needed for enzyme immobilization, polymeric cover membranes, and biocompatible coatings needed to tackle the response by the complex body interface have been developed; wireless transfer and processing of unprecedented data volume have been established; effortless and painless insertion schemes of ever smaller sensors have been realized in order to overcome the concerns of persons with diabetes (PwDs) to use a minimally invasive sensor; and scalable manufacturing technologies of miniaturized minimally invasive sensors have allowed for ever improved reproducibility and increased production volume. Looking ahead, the demands on blood glucose system performance are expected to grow even as the pressures to lower the cost of systems increase. The drive for the future is to continue to push the limits on system performance under real-life conditions while lowering cost, all while finding ways to provide the best medical value to PwDs and healthcare providers. Technical issues of commercially available CGM sensors remain to be solved which currently impede reliable hypo- and hyperglycemic alarms, safe insulin dosing recommendations, or insulin pump control at any time of use. It is realistic to assume that continuous glucose monitoring (CGM) systems will be adopted in the future by a larger population of PwDs. Yet it is also clear that BGM systems will remain a major choice of the great majority of PwDs on a global scale. This review offers a technical overview about user, system, and major regulatory requirements and available suitable sensor technology and demonstrated performance of electrochemical BGM and CGM systems from an industrial R&D perspective.