Early artificial pancreas trials show benefits for kids, teenagers with diabetes overnight

LONDON, Feb. 5, 2010 – In a landmark study in children and teenagers with type 1 diabetes, JDRF-funded researchers at the University of Cambridge showed that using a first-generation artificial pancreas system overnight can lower the risk of low blood sugar emergencies while sleeping, and at the same time improve diabetes control.

Results from the studies are published in the February 5, 2010 issue of The Lancet, available online at www.thelancet.com.

The trials tested the safety and effectiveness of a first-generation artificial pancreas system used overnight in a hospital setting with participants between 5 and 18 years of age with type 1 diabetes. The system combined commercially available blood glucose sensors and insulin pumps, controlled by a sophisticated computer program that determined insulin dosage based on blood glucose levels while the participants slept.

Maintaining recommended blood sugar levels overnight is a major issue for people with type 1 diabetes – and particularly for the families of children with diabetes – because of the possibility of blood glucose dropping dangerously low during sleep and going unnoticed, which can lead to seizures, coma, and in some cases be fatal.

Notably, the Cambridge study showed that the children and teenagers spent twice as much time during the night within targeted blood glucose levels when their diabetes was regulated with the artificial pancreas system than when they followed conventional "manual" therapy. And low blood sugars were minimized.

"These studies show that automated systems not only can help people manage diabetes by maintaining good control, they will also improve quality of life for the people with type 1 diabetes and their families by lowering the risk for hypoglycemia," said Roman Hovorka, Ph.D., from the Institute of Metabolic Science at the University of Cambridge, the principal investigator of the study and lead author of the paper. "These results suggest that closed-loop devices may be able to significantly lower the patient's risk of developing complications later in life by reducing or even overcoming the burden of hypoglycemia."

"Without a doubt, the biggest worry for parents of kids with type 1 diabetes is that their child will have a low blood sugar emergency during the night, when they're hard to identify," said Aaron Kowalski, Ph.D., Assistant Vice President of Metabolic Control at JDRF and Director of the JDRF Artificial Pancreas Project. "This study is proof of principle that diabetes in kids can be safely managed overnight with an artificial pancreas. We need to redouble our efforts to move the artificial pancreas from a concept in the clinic to a reality in the home of kids and adults with type 1."

The first phase of the Cambridge study compared the effectiveness of a simple artificial pancreas system used overnight with standard blood testing and insulin delivery using a pump. It showed that the time participants spent in target blood glucose levels (between 70 mg/dL and 140 mg/dL) improved from 39% to 52%. The second phase of the study evaluated the effects of a using the same artificial pancreas system overnight with the additional variable of the participants eating a particularly large meal, which can impact overnight blood glucose levels. The results were comparable to the first phase of the research. The third phase of the study evaluated the effects of moderately intense exercise, which can also impact blood sugar levels. Using the automated system in this setting showed the greatest improvement in blood sugar control, with the amount of time spent in the target range increasing from 48% to 78%.

"The pooled data from the closed loop studies showed that blood glucose levels were 61% in target, and even increased to 75% in target after midnight when closed-loop became fully effective," said Dr. Hovorka. "Based on these results, this study is a significant step towards an artificial pancreas."

The Cambridge studies were randomized, controlled trials involving 17 children and adolescents conducted at the Wellcome Trust Clinical Research Facility at Addenbrooke's Hospital in Cambridge, United Kingdom over the course of 54 nights. Twelve subjects were used for the first study; 6 subjects were used for the second, and 9 for the third. Some 33 nights were on a closed-loop artificial pancreas system, while 21 nights were controlled (on standard therapy). During the closed-loop studies, continuous glucose measurements were fed into a computer program every 15 minutes, which calculated the insulin infusion rate; the insulin pump was adjusted manually by a research nurse. During control nights, the subject's standard insulin pump settings were applied.

Type 1 diabetes is an autoimmune disease in which the immune system attacks and kills off the cells in the pancreas that produce insulin, a hormone that enables people to convert food into energy. It affects 3 million American children, adolescents, and adults.

To manage their disease, people with type 1 diabetes need to measure their blood sugar multiple times throughout the day (typically by pricking a finger for a drop of blood), and pump insulin or inject themselves multiple times daily to keep blood sugar levels within a healthy range. That daily routine continues for life, because insulin administration does not cure diabetes.

Research has shown that good blood sugar control is a key factor in reducing the risk of the devastating long-term complications of the disease, such as blindness and kidney disease – but that the fear of low blood sugar emergencies often prevents many people from achieving tight control, and remains a constant concern for those who manage their diabetes well. The landmark Diabetes Control and Complications Trial (DCCT) showed that with intensive insulin therapy, excellent blood glucose control was obtained, but at the expense of a considerable increase in hypoglycemia.

Source: Juvenile Diabetes Research Foundation International