[New technologies in diabetology. How far are we from a closed loop?]. / Neue Technologien in der Diabetologie. Wie weit ist es noch bis zum Closed-loop-System?

Today, assistive technologies are highly important in the treatment of diabetes, especially in the therapy of type 1 diabetes. The use of insulin pumps, for example, has become an established form of treatment. Modern insulin pumps offer various functions, such as different basal rate profiles, split delivery of the meal bolus, and integrated bolus calculators. Some pumps are additionally connected to a blood glucose meter or a continuous glucose-monitoring sensor. Several minimally invasive needle-type sensor systems for continuous tissue glucose monitoring are already available. Recent developments aim at increasing the functionality of insulin pumps and the improvements of sensors for continuous glucose monitoring. In addition, many research groups are working on closing the loop between these two components and thus developing an artificial pancreas, which automatically regulates insulin delivery. The first steps have already been taken and bolus calculators or sensor-augmented insulin pumps with suspension of insulin delivery are now available. Many experimental models show promising results. Prior to the implementation of a fully automated system for everyday use, however, partially automated systems that require user input are to be expected. This article aims at giving an overview of the current state of development in the field of diabetes technology.

Continuous glucose monitoring in people with diabetes: the randomized controlled Glucose Level Awareness in Diabetes Study (GLADIS).

AIMS: To investigate the best glucose monitoring strategy for maintaining euglycaemia by comparing self-monitoring of blood glucose with continuous glucose monitoring, with or without an alarm function. METHODS: A 100-day, randomized controlled study was conducted at four European centres, enrolling 160 patients with Type 1 or Type 2 diabetes, on multiple daily insulin injections or continuous subcutaneous insulin infusion. Participants were randomized to continuous glucose monitoring without alarms (n = 48), continuous glucose monitoring with alarms (n = 49) or self-monitoring of blood glucose (n = 48). RESULTS: Time spent outside the glucose target during days 80-100 was 9.9 h/day for the continuous glucose monitoring without alarms group, 9.7 h/day for the continuous glucose monitoring with alarms group and 10.6 h/day for the self-monitoring of blood glucose group (P = 0.18 and 0.08 compared with continuous glucose monitoring without and with alarms, respectively).The continuous glucose monitoring with alarms group spent less time in hypoglycaemia compared with the self-monitoring of blood glucose group (1.0 h/day and 1.6 h/day, respectively; 95% CI -1.2 to -0.1; P = 0.030). Among those treated with continuous subcutaneous insulin infusion, time spent outside the glucose target was significantly different when comparing continuous glucose monitoring without alarms and self-monitoring of blood glucose (-1.9 h/day; 95% CI -3.8 to 0.0; P = 0.0461) and when comparing continuous glucose monitoring with alarms and self-monitoring of blood glucose (-2.4 h/day; 95% CI -4.1 to -0.5; P = 0.0134). There was no difference in HbA1c reduction from baseline in the three groups; however, the proportion of participants with a reduction of ≥ 6 mmol/mol (≥ 0.5%) was higher in the continuous glucose monitoring without alarms (27%) and continuous glucose monitoring with alarms groups (25%) than in the self-monitoring of blood glucose group (10.6%). CONCLUSIONS: This study shows that the use of continuous glucose monitoring reduces time spent outside glucose targets compared with self-monitoring of blood glucose, especially among users of insulin pumps.

Glucose monitoring by microdialysis: performance in a multicentre study.

AIMS: The aim of this study was to assess the performance of the Continuous Research Tool (CRT) in a multicentre clinical-experimental study. METHODS: Three patient groups totalling 28 subjects with diabetes [group A 10 Type 1 (Ulm), group B 10 Type 1 (Neuss), group C eight Type 2 (Aarhus)] participated in this trial. Two CRT microdialysis probes were inserted in parallel in the abdominal subcutaneous tissue for 120 h in each subject. In subjects in group A, glucose excursions were induced on one study day and those in group B underwent a glucose clamp (eu-, hypo- or hyperglycaemic) on one study day. CRT data were calibrated once with a retrospective calibration model based on a run-in time of 24 h and three blood glucose measurements per day. RESULTS: All analysable experiments, covering a broad range of blood glucose values, yielded highly accurate data for the complete experimental time with a mean relative absolute difference of 12.8 +/- 6.0% and a predictive residual error sum of squares of 15.6 +/- 6.3 (mean +/- SD). Of all measurement results, 98.2% were in zones A and B of the error grid analysis. The average absolute differences were 1.14 mmol/l for Type 1 and 0.88 mmol/l for Type 2 diabetic patients. Relative absolute differences were 16.0% for Type 1 and 12.6% for Type 2 diabetic patients. CONCLUSIONS: These results demonstrate that this microdialysis system allows reliable continuous glucose monitoring in patients with diabetes of either type.

Recent advances in continuous glucose monitoring.

Continuous glucose monitoring, providing more detailed information on glucose excursions than single spot measurements, should help to improve the therapy in diabetic patients and is also required for feedback-controlled insulin delivery. At the Institute for Diabetes-Technology in Ulm, founded by EF Pfeiffer, a portable glucose sensor for continuous tissue glucose monitoring has been developed. The combination of microdialysis and enzymatic amperometric glucose measurement implemented in this device marked a break-through in achieving reliable and precise continuous tissue glucose monitoring. In several studies, we have demonstrated that continuous subcutaneous glucose monitoring for up to 72 hours is feasible under 'in-house' and 'daily life' conditions in diabetic patients. The measured tissue glucose concentrations correlated closely to glucose control measurements in venous and capillary blood. A reliable continuous glucose monitoring device is a prerequisite for the development of an artificial pancreas. Our group developed an algorithm for subcutaneous application of the fast acting insulin analogon lispro. In experiments performed over 7 and 24 hours good metabolic control was achieved by algorithm-based insulin application. In addition, the algorithm was able to maintain acceptable metabolic control during and after moderate physical exercise. Further work is needed to optimize continuous tissue glucose monitoring systems and to develop a closed loop system for insulin application based on continuously measured tissue glucose concentrations.