The bihormonal artificial pancreas Development and evaluation of a novel treatment for type 1 diabetes

Fully automated glucose control with a bihormonal artificial pancreas (AP), using insulin to lower the blood glucose concentration and glucagon to increase glucose, was previously demonstrated to be feasible with prototypes that consisted of modified commercially available devices. The aim of this thesis was to contribute to the development of a product version of the bihormonal AP and to evaluate its performance and safety in adults with type 1 diabetes. To provide an overview and discussion of safety and design requirements of the AP, we performed a structured literature search and extended the discussion with our own experiences in developing AP systems. We assessed the pharmacokinetics and pharmacodynamics of different doses of glucagon. We found a dose-dependent response at both hypoglycemic and non-hypoglycemic blood glucose levels. The results of this study support the use of glucagon in the AP to prevent and correct mild hypoglycemia. Furthermore, the role of psychosocial factors in the patient acceptance of the AP was investigated using a questionnaire. We found that participants had a high intention to use the bihormonal AP and that product characteristics were generally more strongly related to acceptance than technology readiness. We performed a pilot study with a novel prototype of the bihormonal AP and the results were used to further improve the AP. In the final study, the bihormonal AP was demonstrated to provide superior glucose control compared with insulin pump therapy and was safe. The available clinical evidence resulted in the first CE-mark for a bihormonal AP.