Artificial Pancreas Project at Cambridge

1. R. Hovorka, J.M. Allen, L.J.Chassin, A. De Palma, D. Elleri, J. Harris, J.F. Hayes, T. Hovorka, K. Kumareswaran, A.F. Larsen, J. Mangat, M. Nodale, M.E. Wilinska, C.L. Acerini, D.B.Dunger, M.L. Evans, H.R. Murphy Institute of Metabolic Science, Department of Paediatrics and Department of Medicine, University of Cambridge, United Kingdom Artificial Pancreas Project at Cambridge CLOSED LOOP IN CHILDREN OVERVIEW CLOSED LOOP IN ADULTS • The Artificial Pancreas Project started in 2007 and the first three studies evaluated the manual closed loop (CL) in children and adolescents with T1D. • Type 1 Diabetes (T1D) is one of the most common chronic conditions in developed nations. To improve glucose control, quality of life and prevent long term complications, new tools are being developed. • The Artificial Pancreas Project at the University of Cambridge focuses on closed-loop (CL) overnight insulin delivery in people with T1D. • It combines a purpose-made model-predictive control (MPC) algorithm with an off-the-shelf continuous glucose monitor and an insulin pump. Sample of overnight algorithm CL control in adults • The first CL study in adults is underway. Preliminary analyses demonstrate improved efficacy under CL control, as compared to conventional pump therapy. Paediatric Efficacy Study • The first clinical study compared the continuous subcutaneous insulin infusion (CSII) against CL in 12 children and adolescents with T1D. • The results showed improved glucose control with CL whilst reducing the risk of hypoglycaemia [1 ] (see figure below). • The second study will compare overnight CL insulin delivery with CSII following an evening of drinking alcohol, in particular assessing glucose control and frequency of hypoglycaemia. CLOSED LOOP IN PREGNANCY • Optimising glucose control is particularly challenging in pregnancy. • To inform CL algorithms specific for pregnancy, physiological studies of glucose gut absorption are currently underway. Diet Study • The second study evaluated the performance of the CL system following a rapidly and slowly absorbed large meal. A subset of 6 subjects from the first study participated. • The results demonstrated that CL is safe and efficacious in controlling overnight glucose following the ingestion of a large meal irrespective of its composition [2]. FUTURE : HOME STUDIES AUTOMATED CLOSED LOOP IN CHILDREN • Having completed almost 100 overnight studies, the research team are focusing on progression to home studies. • The first adult and paediatric studies using overnight automated CL in the home setting (prototype pictured) will commence Autumn 2009. Exercise Study • The progression from manual to fully automated CL system is under evaluation in the Wellcome Trust Clinical Research Facility (WTCRF). • The aim is to evaluate the safety and efficacy of automated overnight CL when initiated before an evening meal or before bed. • The third study tested the CL in post- exercise conditions in 9 subjects. • Overnight CL with MPC following afternoon exercise avoids hypoglycaemia and increases time spent in target glucose range twofold [3]. Glossary AP - Artificial pancreas CL - Closed-loop system APCam - AP project at Cambridge T1D - Type 1 diabetes CSII - Continuous Subcutaneous Insulin Infusion MPC - Model-Predictive Control References: [1]Hovorka R et al, ADA June 2008 [2]Hovorka R et al, EASD Sept 2008 [3]Hovorka R et al, ATTD Feb 2009 Acknowledgements Grateful thanks are due to the many children, young people and adults who have participated in the studies and to the staff of the Wellcome Trust Clinical Research Facility without whose assistance the studies could not have taken place. Thanks also for the support given by JDRF, Diabetes UK, MRC CORD, EFSD and NIHR Cambridge Biomedical Research Centre.