The Juvenile Diabetes Research Foundation has today announced an innovative partnership to develop an automated system to help people with type 1 diabetes better control their disease – the first step on the path to what would be among the most revolutionary advancements in treating type 1 diabetes: the development of an artificial pancreas, a fully automated system to dispense insulin to patients based on real-time changes in blood sugar levels.

JDRF has formed a partnership with Animas, a Johnson & Johnson company and a leading manufacturer and distributor of insulin delivery and glucose management systems.

The objectives of the partnership, a major industry initiative within the JDRF Artificial Pancreas Project, are to not only produce the automated system but to conduct extensive clinical trials for safety and efficacy and submit the product to the regulatory authorities for approval and subsidy.

“If successful, the development of this first-generation system would begin the process of automating how people with diabetes manage their blood sugar,” said Mike Wilson Chief Executive Officer of JDRF Australia.

“Ultimately, an artificial pancreas will deliver insulin as needed, minute-by-minute, throughout the day to maintain blood sugars within a target range.  But even this early system could bring dramatic changes in the quality of life for the 140,000 Australians living with type 1 diabetes, beginning to free kids and adults from testing, calculating and treating themselves throughout the day.”

Dr. Alan Lewis, CEO and President of JDRF International noted that “JDRF will provide $US8 million in funding over the next three years for this project, with a target of having a first-generation system ready within four years.”

Currently, type 1 diabetes is managed with insulin injected from a needle or an insulin pump and regular fingerprick blood tests. Unfortunately, blood glucose levels can change rapidly in response to hundreds of different triggers making it extremely difficult to accurately predict the amount of insulin required.

This first-generation system will be partially automated, utilising an insulin pump connected wirelessly with a continuous glucose monitor (CGM). The CGM continuously reads glucose levels through a sensor with a hair-thin sensor wire inserted just below the skin, typically on the abdomen.  The sensor would transmit those readings to the insulin pump, which delivers insulin through a small tube or patch on the body.  The pump would house a sophisticated computer program that will address safety concerns during the day and night, by helping prevent hypoglycemia and extreme hyperglycemia.  It would slow or stop insulin delivery if it detected blood sugar was going too low and would increase insulin delivery if blood sugar was too high.

For example, the system would automatically discontinue insulin delivery to help prevent hypoglycemia, and then automatically resume insulin delivery based on a specific time interval (i.e., 2 hours) and/or glucose concentration.  It will also automatically increase insulin delivery to reduce the amount of time spent in the hyperglycemic range and return to a pre-set basal rate once glucose concentrations have returned to acceptable levels.

In this early version of an automated diabetes management system, the patient would still need to manually instruct the pump to deliver insulin at times, (i.e. around meals).  But this “hypoglycemia-hyperglycemia minimiser” system would represent a significant step forward in diabetes management, and could provide immediate benefits in terms of blood sugar control, by minimising dangerous highs and lows.

The Artificial Pancreas Project was established by JDRF in 2005. You can find out more at www.jdrf.org/artificialpancreas.

You can help speed up the process of bringing the Artificial Pancreas to reality. Support the Artificial Pancreas Project by giving to JDRF. Every dollar will help bring research to reality.

The first study showed that regular use of CGMs is the main factor in achieving better diabetes control, rather than the age of people using the monitors, or other demographic, clinical, or psychosocial factors.  The second study showed that people using CGMs were able to achieve good diabetes control while at the same time actually lowering the incidence of hypoglycemia.

This is significant because good diabetes control is critical for reducing the risk of serious health complications associated with diabetes, like stroke, blindness, heart disease and kidney failure. However, this tight control can be difficult to achieve and is associated with increased occurrence of hypoglycemia, which is dangerously low blood glucose levels that can lead to coma or death. These results suggest that regular use of CGMs can overcome this risk.

“Based on these results and previous JDRF CGM trials published over the past 12 months, we know that these devices can help people get in control of their diabetes, help people already managing their disease maintain good control, and help people stay in control over an extended period of time, while lowering their risk for hypoglycemia,” said Dr. William V. Tamborlane, of Yale University, a co-chair of the JDRF funded study.

JDRF Australia CEO Mike Wilson said these results were important for Australia. “Consistent use of CGMs is now proven to have significant benefits for all people with type 1 diabetes.”

“CGMs are expensive for Australians but this research suggests that widespread use would deliver substantial savings for our health system in the long term. The type 1 diabetes community needs maximum access to technology that will improve both their health and their quality of life.”

These trials are part of JDRF International’s Artificial Pancreas Project. More information is available online at http://www.artificialpancreas.org. The findings of the two JDRF studies from the major multi-center trial have been published online by Diabetes Care at http://care.diabetesjournals.org/papbyrecent.shtml.

About CGM Devices

CGM devices provide both a real-time snapshot of the glucose levels of a person with diabetes, as well as trend information on whether glucose is moving upwards or downwards, and how fast.  Devices also provide warnings when the glucose is becoming too high or too low.

There is extensive research to show that tight blood glucose control is the best way to prevent the onset of type 1 diabetes complications such as kidney failure, retinopathy and heart disease. According to results from the Diabetes Complications and Control Trial, every one point reduction in HbA1C reduces the risk of long-term complications by approximately 40%.

Unfortunately, research has also shown that one of the hurdles to tight blood sugar control is the risk of hypoglycemia – both real and perceived.

Over the past 15 years the use of different insulin analogs as well as improvements in insulin pumps and blood glucose monitoring has had a positive impact on the ability of people to achieve blood sugar control targets. The rates of severe hypoglycemia, however, remain high and occurrence of such events is often followed by a decline of glycemic control due to fears of further hypoglycemic episodes.

In two multi-centre clinical trials – the first concentrating on people with bad glycemic control and the second on people who intensively manage their blood sugars – JDRF researchers have now demonstrated that an excellent solution to this problem is the use of a continuous glucose monitor, or CGM.

According to these trials, people using CGM spent two hours more time per day in the target blood sugar range of 3.9 to 10.0 mmol/l compared with people using fingerprick testing alone. They also found that CGM subjects had a significant overall improvement in HbA1C over time without an increased number of hypoglycemic attacks.

CGM devices are worn in a similar fashion to an insulin pump and provide both a real-time snapshot of glucose levels as well as trend information on whether glucose is moving up or down. They can also provide a warning when glucose is becoming too high or too low.

The continuous glucose monitor is a key component of the JDRF international Artificial Pancreas Program and these results take researchers one step closer to making the artificial pancreas a reality.

Diabetes Care published online 25th May 2009

According to the JDRF study, using CGM devices enables people who have achieved excellent control (with HbA1c levels below 7 percent) to continue to tightly manage their diabetes while cutting down on the frequency of low blood sugars, called hypoglycemia. Research has shown that good blood sugar control is a key factor in reducing the risk of the devastating long-term complications of type 1 diabetes, 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 type 1 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. Today, the JDRF study has shown that, with CGM, hypoglycemia can be reduced while maintaining excellent blood sugar control.

The CGM study was a randomized and controlled trial involving 129 adults and children ranging in age from 8 to 69 years old at 10 sites, including the Atlanta Diabetes Associates, the Joslin Diabetes Center, Kaiser Permanente Southern California, Nemours Children’s Clinic – Jacksonville, FL, the Lucile Packard Children’s Hospital at Stanford University, the Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver, the University of Iowa, the University of Washington, and Yale University, and coordinated by the Jaeb Center for Health Research in Tampa, Florida. Participants all had good diabetes control when they enrolled in the trial, and were randomly assigned to either a group that used CGM devices or one using standard finger-stick glucose testing for 26 weeks.

“The research suggests that CGM devices helped people who were already doing an excellent job of managing their type 1 diabetes continue to do so, while lowering the risk of pushing their blood sugar so low it causes hypoglycemia, which can be life threatening,” said Dr. Bruce Bode, Atlanta Diabetes Associates and one of the lead authors of the Diabetes Care paper. “These trials are showing that CGM not only helps people get into control, which can have a significant positive impact on lowering the risk of complications, but it enables them to stay in control without increasing the near-term risk of hypoglycemia. That’s terrific news for people with type 1 diabetes and their families.”

(People with type 1 diabetes try to maintain their blood sugar levels between 70 mg/dL and 180 mg/dL. When blood sugar becomes very low, people can become confused, lethargic, and even slip into a coma or die. Very high blood sugars can also be dangerous. And long term, lack of control increases the risk of developing devastating complications, including eye, kidney, nerve, and heart disease. HbA1c is a measure of long term blood sugar control; standards of good control are generally below 7% for adults, and below 7.5% to 8% for children, depending on age. According to the DCCT findings, every one point reduction in HbA1c reduces the risk of long-term complications by approximately 40%.)

According to the study, for the people using CGM devices the time the blood sugar level was below 70 mg/dL decreased by 37 minutes a day. This compared with a decrease in the control group of only 5 minutes a day. In other words, people in the CGM group spent almost two hours more time per day in the target blood sugar range of 71 to 180 mg/dL compared with the control group, and about half an hour less time per day with glucose values in the potentially dangerous hypoglycemia range. The authors demonstrated a number of other significant benefits in this population including:

• more people in the CGM group had an improvement in HbA1c of more than 0.3% (31% versus 5% in the control group)
• fewer had a worsening of HbA1c greater than 0.3% (28% versus 52%)
• more CGM users had a HbA1c level below 7% at 26 weeks (88% versus 63%)
• more people in the CGM group than the control group had a decrease in HbA1c of more than 0.3% without experiencing a severe hypoglycemic event (28% versus 5%).

Encouragingly, similar beneficial results were seen in children, adolescents, and adults spanning the ages of 8 to 69 years.

Dr. Aaron Kowalski, Program Director for Metabolic Control at JDRF, explained that in planning this study, the change in HbA1c was not selected as the primary outcome measure because the researchers did not anticipate being able to lower HbA1c levels in the CGM group, given their already exquisite level of control. He noted that the study group expected that there might even be small and clinically insignificant increases in HbA1c values in the CGM group if the devices were able to help them reduce the frequency of glucose levels below 70 mg/dL. Instead, the CGM group was able to maintain HbA1c levels with less biochemical hypoglycemia, whereas HbA1c levels rose over time in the control group. He noted that all the HbA1c outcomes favored the CGM over the control group.

Major eligibility criteria for the study included people over the age of 8 who had type 1 diabetes for at least one year, who either used an insulin pump or took at least three daily insulin injections, and had HbA1c levels below 7.0%. Subjects in the control group were given blood glucose meters and test strips and asked to perform blood glucose monitoring at least four times daily, and met with study personnel as often as the CGM group.

The study is the second major publication resulting from JDRF’s groundbreaking CGM trials, established to clinically document the benefits of CGM devices in helping people with type 1 diabetes manage their disease more effectively. In results published last fall in The New England Journal of Medicine, the JDRF Continuous Glucose Monitoring Study Group reported that CGM substantially improved blood sugar levels without increasing the frequency of hypoglycemia in adults over 25 years of age in a randomized trial of 322 adults and children with type 1 diabetes and HbA1c levels above 7 percent. (Like virtually every other study of a new drug or device in the treatment of type 1 diabetes, because lowering of HbA1c was the primary outcome of interest, that study excluded individuals already reaching target HbA1c levels lower than 7 percent. As a result, the study group also conducted a separate, concurrent randomized trial to evaluate the efficacy and safety of CGM in adults and children with type 1 diabetes who already had successfully achieved HbA1c levels less than 7 percent with intensive insulin therapy.) More information on the initial results of JDRF’s CGM trials and on the Artificial Pancreas Project is available online at http://www.artificialpancreas.org/.

Dr. Kowalski noted that over the past 15 years, the use of rapid and long-acting insulin analogs, improvements in insulin pumps, and more frequent home blood glucose monitoring have had a positive impact on the ability of people with type 1 diabetes to achieve blood sugar control targets. However, the rates of severe hypoglycemia remain too high and the occurrence of such events is often followed by a decline in glycemic control due to fears of further hypoglycemic episodes. Hypoglycemia remains the major limiting factor for people with type 1 diabetes in trying to achieve and maintain good blood sugar control. These study results are extremely encouraging in showing that hypoglycemia can be reduced without sacrificing glycemic control.

For more information, contact JDRF International:

William J. Ahearn
Ph: +(1 212) 479-7531
E-mail: wahearn@jdrf.org

Joana Casas
Ph: +(1 212) 479-7560
E-mail: mcasas@jdrf.org