Is an artificial pancreas (closed‐loop system) for Type 1 diabetes effective?

The artificial pancreas is now a viable treatment option for people with Type 1 diabetes and has demonstrated improved glycaemic outcomes while also reducing the onus of self‐management of Type 1 diabetes. Closed‐loop glucose‐responsive insulin delivery guided by real‐time sensor glucose readings can accommodate highly variable day‐to‐day insulin requirements and reduce the hypoglycaemia risk observed with tight glycaemic control in Type 1 diabetes. In 2011, the James Lind Alliance research priorities for Type 1 diabetes were produced and priority 3 was to establish whether an artificial pancreas (closed‐loop system) for Type 1 diabetes is effective. This review focuses on the progress that has been made in the evolution of closed‐loop systems as an effective treatment option for Type 1 diabetes. Development of closed‐loop systems has advanced from feasibility evaluations in highly supervised settings over short periods, to clinical studies in free‐living, unsupervised conditions lasting several months. The approval in the USA of the first hybrid closed‐loop system (MiniMed® 670G pump, Medtronic, Northridge, CA, USA) in 2016 for use in Type 1 diabetes reflects these advancements. We discuss the evidence from clinical studies that closed‐loop systems are effective with improved glycaemic outcomes, reduced hypoglycaemia and had positive end‐user acceptance in children, adolescents, adults and pregnant women with Type 1 diabetes. We also present the outlook for future closed‐loop systems in the treatment of Type 1 diabetes and identify the challenges facing the wide‐spread clinical adoption of this technology.

[1]  A H Clemens,et al.  The development of Biostator, a Glucose Controlled Insulin Infusion System (GCIIS). , 1977, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[2]  Joseph Leitschuh,et al.  Randomized Outpatient Trial of Single- and Dual-Hormone Closed-Loop Systems That Adapt to Exercise Using Wearable Sensors , 2018, Diabetes Care.

[3]  Roman Hovorka,et al.  Closed-Loop Insulin Delivery during Pregnancy in Women with Type 1 Diabetes. , 2016, The New England journal of medicine.

[4]  Glucose Concentrations of Less Than 3.0 mmol/L (54 mg/dL) Should Be Reported in Clinical Trials: A Joint Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes , 2016, Diabetes Care.

[5]  Bruce W Bode,et al.  Safety of a Hybrid Closed-Loop Insulin Delivery System in Patients With Type 1 Diabetes. , 2016, JAMA.

[6]  S. Patek,et al.  Closed-Loop Artificial Pancreas Using Subcutaneous Glucose Sensing and Insulin Delivery and a Model Predictive Control Algorithm: The Virginia Experience , 2009, Journal of diabetes science and technology.

[7]  Marc D. Breton,et al.  Closed-Loop Control During Intense Prolonged Outdoor Exercise in Adolescents With Type 1 Diabetes: The Artificial Pancreas Ski Study , 2017, Diabetes Care.

[8]  B. Perkins,et al.  Effect of artificial pancreas systems on glycaemic control in patients with type 1 diabetes: a systematic review and meta-analysis of outpatient randomised controlled trials. , 2017, The lancet. Diabetes & endocrinology.

[9]  D. Klonoff,et al.  Threshold-based insulin-pump interruption for reduction of hypoglycemia. , 2013, The New England journal of medicine.

[10]  A J Sutton,et al.  Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta‐analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion , 2008, Diabetic medicine : a journal of the British Diabetic Association.

[11]  C. Farrington Psychosocial impacts of hybrid closed‐loop systems in the management of diabetes: a review , 2018, Diabetic medicine : a journal of the British Diabetic Association.

[12]  Ahmad Haidar,et al.  Efficacy of single-hormone and dual-hormone artificial pancreas during continuous and interval exercise in adult patients with type 1 diabetes: randomised controlled crossover trial , 2016, Diabetologia.

[13]  T. Jones,et al.  Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized clinical trial. , 2013, JAMA.

[14]  Eyal Dassau,et al.  Intraperitoneal insulin delivery provides superior glycaemic regulation to subcutaneous insulin delivery in model predictive control‐based fully‐automated artificial pancreas in patients with type 1 diabetes: a pilot study , 2017, Diabetes, obesity & metabolism.

[15]  Janet M. Allen,et al.  Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial , 2010, The Lancet.

[16]  R. Hovorka,et al.  Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis , 2018, British Medical Journal.

[17]  Eyal Dassau,et al.  International Consensus on Use of Continuous Glucose Monitoring , 2017, Diabetes Care.

[18]  R. Rabasa-Lhoret,et al.  The challenges of achieving postprandial glucose control using closed‐loop systems in patients with type 1 diabetes , 2018, Diabetes, obesity & metabolism.

[19]  Roman Hovorka,et al.  Closed-loop insulin delivery: from bench to clinical practice , 2011, Nature Reviews Endocrinology.

[20]  A. H. Kadish,et al.  AUTOMATION CONTROL OF BLOOD SUGAR. I. A SERVOMECHANISM FOR GLUCOSE MONITORING AND CONTROL. , 1964, The American journal of medical electronics.

[21]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[22]  Roman Hovorka,et al.  Home Use of an Artificial Beta Cell in Type 1 Diabetes. , 2015, The New England journal of medicine.

[23]  Tadej Battelino,et al.  Closed-loop glucose control in young people with type 1 diabetes during and after unannounced physical activity: a randomised controlled crossover trial , 2017, Diabetologia.

[24]  Howard C. Zisser,et al.  Outcome Measures for Artificial Pancreas Clinical Trials: A Consensus Report , 2016, Diabetes Care.

[25]  Ahmad Haidar,et al.  Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: an open-label randomised controlled crossover trial. , 2015, The lancet. Diabetes & endocrinology.

[26]  Ahmad Haidar,et al.  Outpatient 60‐hour day‐and‐night glucose control with dual‐hormone artificial pancreas, single‐hormone artificial pancreas, or sensor‐augmented pump therapy in adults with type 1 diabetes: An open‐label, randomised, crossover, controlled trial , 2017, Diabetes, obesity & metabolism.

[27]  W. Kenneth Ward,et al.  Novel Use of Glucagon in a Closed-Loop System for Prevention of Hypoglycemia in Type 1 Diabetes , 2010, Diabetes Care.

[28]  J. Petrie,et al.  Setting research priorities for Type 1 diabetes , 2012, Diabetic medicine : a journal of the British Diabetic Association.

[29]  Moshe Phillip,et al.  Feasibility study of automated overnight closed-loop glucose control under MD-logic artificial pancreas in patients with type 1 diabetes: the DREAM Project. , 2012, Diabetes technology & therapeutics.

[30]  Lotty Hooft,et al.  Continuous glucose monitoring systems for type 1 diabetes mellitus. , 2012, The Cochrane database of systematic reviews.

[31]  Janet M. Allen,et al.  Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies , 2011, BMJ : British Medical Journal.

[32]  J. Pickup,et al.  Insulin-pump therapy for type 1 diabetes mellitus. , 2012, The New England journal of medicine.

[33]  Norman Fleischer,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. , 1993 .

[34]  H Keen,et al.  Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia. , 1978, British medical journal.

[35]  Dana Lewis,et al.  Real-World Use of Open Source Artificial Pancreas Systems , 2016, Journal of diabetes science and technology.