Type 1 diabetes is one of the most common chronic diseases in the paediatric population. This year, 78,000 children worldwide were diagnosed with Type 1 diabetes, and the incidence in children younger than 5 years is rising annually by around 3% in many countries (1).Intensification of insulin therapy is essential to tighten glycaemic control and protect from long-term vascular complications (2), but this is often hindered by hypoglycaemia.
Research at Cambridge has focuses on the development of a closed-loop insulin delivery system for treatment of type 1 diabetes (3). A closed-loop system, also known as Artificial Pancreas, is a medical device that combines continuous glucose monitoring and insulin pump therapy via a computer-based algorithm dictating insulin delivery independent of patient supervision. This approach differs from current insulin therapy by providing a continuous glucose-regulated insulin replacement, with the aim to achieve normoglycaemia whilst reducing the risk of hypoglycaemia.
Previous and ongoing clinical studies at Cambridge are demonstrating the effectiveness and safety of closed-loop insulin delivery in children and adolescents with type 1 diabetes (4;5). The initial focus has been on overnight glucose control, as the risk of hypoglycaemia is greater overnight when the counter-regulatory response to hypoglycaemia is blunted. Through a number of clinical studies involving around 50 children and adolescents, overnight closed-loop therapy was evaluated under different scenarios (afternoon exercise, evening meals of different size and composition) and it was shown to increase the time when glucose levels were in the target range and reduce the time spent at low glucose levels. These studies were performed at the clinical research centre with constant supervision by research staff.
More recently, the overnight closed-loop system was evaluated in 16 adolescents aged 12 to 18 years over three weeks in the home settings (Figure 1). For the first time, a closed-loop system was evaluated under real life conditions over multiple nights, without constant supervision by the research team. Young participants connected to the automated closed-loop at bedtime and disconnected it in the morning before breakfast, with no limitation in the types of activity (exercise, school-related activities, meals) they were engaged in during the day. It is crucial to demonstrate benefits of closed-loop therapy under real-life conditions to pave the way for a wider use of closed-loop therapy as integrated part of daily diabetes management.
Achievement of optimal glycaemic control in toddlers and pre-school children with type 1 diabetes presents unique challenges. Unpredictable food intake and physical activity together with high insulin sensitivity may complicate glycaemic control and predispose the young child to severe hypoglycaemia. At present, the safety and efficacy of overnight closed-loop therapy is being evaluated in twelve children aged 2 to 6 years in the clinical research facility. Closed-loop with standard insulin strength is compared to closed-loop with diluted insulin, as we hypothesise that diluted insulin could enhance accuracy of insulin delivery at low insulin doses, like those needed in young children.
In conclusion, paediatric diabetes research at Cambridge has focused on the development of closed-loop systems for glucose control, evaluated in a series of clinical trials, encompassing ever increasing technological sophistication and treatment objectives. Evaluation of closed-loop therapy in the home settings was an important step for closed-loop therapy to be considered as valuable alternative treatment option for children and adolescents with type 1 diabetes in the near future.
1. Patterson,CC, Dahquist,GG, Gyurus,E, Green,A, Soltesz,G: Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet 373:2027-2033, 2009
2. Diabetes Control and Complication Trial Study Group (DCCT): The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes-mellitus. N Engl J Med 329:977-986, 1993
3. Elleri,D, Dunger,DB, Hovorka,R: Closed-loop insulin delivery for treatment of type 1 diabetes. BMC Med 120:1-9, 2011
4. Hovorka,R, Allen,JM, Elleri,D, Chassin,LJ, Harris,J, Xing,D, Kollman,C, Hovorka,T, Larsen,AM, Nodale,M, De,PA, Wilinska,ME, Acerini,CL, Dunger,DB: Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet 375:743-751, 2010
5. Elleri,D, Allen,JM, Biagioni,M, Kumareswaran,K, Leelarathna,L, Caldwell,K, Nodale,M, Wilinska,ME, Acerini,CL, Dunger,DB, Hovorka,R: Evaluation of a portable ambulatory prototype for automated overnight closed-loop insulin delivery in young people with type 1 diabetes.Pediatr Diabetes 13:449-453, 2012