Modeling of insulin and blood glucose as accelerometry data and heart rate during stress and physical activity in type 1 diabetic relationships to improve the performance of Artificial Pancreas

Type 1 diabetes affects 180,000 people in France, increasing 3-4% per year and with a significant number of children and teenagers. Patients must perform self-administration of insulin several times daily at doses based on their carbohydrate intake and blood glucose reading, with the level of physical activity (PA), emotional and psychosocial stress also being factors. These last factors are the most difficult to manage, even for patients completely familiar with this aspect of their treatment. PA is the cause of most hypoglycaemic accidents and is a contributing factor in blood sugar imbalance and its attendant ills. Recurrence of hypoglycaemic episodes can significantly impair quality of life. Increased stress levels will have an opposing effect, reducing the effectiveness of insulin and leading to higher blood glucose levels. Maintaining blood glucose levels in the correct range with all these factors is thus very challenging for the patients. However failure to maintain the range will lead, on top of hypoglycaemic events, to severe complications (retinopathy, amputations, renal and cardiac failures,…) There are several avenues being explored for curing type 1 diabetes (stem cells, islet grafts,…) however they are either unpractical for a whole population, prohibitively expensive or will not be available before many years. As such, the best approach is to improve the current treatment. One possible solution is an artificial pancreas, a system that mimicks the insulin delivery of a non-diabetes person. The Diabeloop consortium is currently developing such a system, which incorporates continuous glucose measurement, a patient interface (to input meal, PA and other patient data), a calculator to determine insulin pump settings, and telemonitoring capability. This project started in 2011, and in 2014 2 clinical studies demonstrated the effectiveness of a prototype on 35 patients. The consortium is targeting 2018 for availability to the patients of the system. However during the development of this Artificial Pancreas system the PA and Emotional Stress have been problematic. We know they are key factors in the everyday life of diabetic patients, but their effects are under-represented and not very well studied in the clinical studies and literature. In particular the physiological models of insulin and glucose supporting the algorithms do not account for these 2 factors. The Diabeloop_AP ANR project proposes to better understand the impact of PA and emotional stress and to develop an innovative model enabling their integration using continuous measurement of heart rate and accelerometry. To do this we will rely on a number of existing databases we have access to (including from a previous ANR project, “SVELTE”) as well as collect specific data initially with patients. We will then build upon existing, well described physiological models to improve them by including these 2 factors. Finally we will validate this new model during a clinical study. To achieve this result we assembled a strong team, with partners bringing complementary expertise to the project: the CEA for the algorithm and modelling, the CRHN-RA with their long experience in Physical Activity with regards to Diabetes, CERITD with their Artificial Pancreas and long history of type 1 research, and CHSF and CHU Grenoble bringing their clinical and diabetes expertise. The results of the Diabeloop_AP ANR project would be integrated in the second version of the Diabeloop Artificial Pancreas system to further improve it. It can also be included in other Artificial Pancreas systems and be used to improve the guidance and training of diabetes patients, whether they use an Artificial Pancreas or not. As such this research project will have a strong medical benefit by reducing hypoglycaemic events, severe complications and improve everyday quality of life for a large number of type 1 diabetes patients.