For the first time ever in parallel experiments in both France and Italy, two participants with type 1 diabetes were able to control their diabetes using an artificial pancreas system in a real-life setting. Participants spent a night at a hotel and eating at a restaurant while using the device, and attained near-normal glucose levels. The research team used approved insulin pumps and continuous glucose monitors, which were controlled by a hand-held device and monitored by the investigators to ensure safety.

These were the first outpatient trials using an approach developed by the JDRF-supported International Artificial Pancreas Study Group, an international research group. Previous trials have all been conducted in an in-patient setting. Eight more patients enrolled in the trial will begin outpatient testing in coming weeks.

The advancement of an artificial pancreas is a priority for the t1d community. People with t1d constantly have to determine the right amount of insulin to dose at the right time, multiple times a day. Yet even with diligent monitoring, a portion of the day can still be spent with high or low blood sugar, placing them at risk.

Low Glucose Suspend Technology approved in United States

In-home trials of low glucose suspend technology have been approved for the first time in the U.S. An LGS system is a version of an insulin pump which suspends insulin delivery when a monitor indicates a person with diabetes has or is projected to have low glucose levels.

These systems are the first step toward an artificial pancreas, a device that could transform the lives of individuals with t1d. By automating detection of blood sugar levels and delivery of insulin in response to those levels, an artificial pancreas has the potential to transform the lives of people with type 1 diabetes.

JDRF Australia CEO Mike Wilson says these steps towards using an artificial pancreas in a real-life setting are encouraging.

“This technology has great potential to improve the lives of the t1d community, but it will only be successful if it can be used as people go about their daily lives. These two developments are a big step forward in achieving that goal”.

1. Joslin 50-year Medallist study uncovers protective factors against diabetes complications
2. Clinical trials of an overnight artificial pancreas system improve glycemic control
3. Transplantation of encapsulated stem cells reduces glucose levels in diabetic mice

Joslin 50-year Medallist study uncovers protective factors against diabetes complications

A JDRF-funded study has characterised a subgroup of people who have had diabetes for 50 years or more, who remain free from complications. This population is likely enriched for protective factors against complications, and uncovering any protective mechanisms against complications might prove useful to the general population with diabetes.

The study of 351 Joslin Medallists (who have survived 50 years or more of type 1 diabetes) assessed retinopathy, nephropathy, neuropathy, and cardiovascular disease in relation to a range of risk factors. It was found that a high proportion of Joslin Medallists remained free of diabetes complications and that, in this group, glycaemic control was unrelated to the development of complications. Specific Advanced Glycation Endproducts (AGE) combinations were strongly associated with complications, indicating a link between AGE formation or processing with the development of complications.

Clinical trials of an overnight artificial pancreas system improve glycemic control

Two JDRF-funded clinical trials have been run to compare the safety and efficacy of an overnight Artificial Pancreas system with conventional insulin pump therapy. Published in the British Medical Journal, the trials tested 24 adults on an ‘eating in’ scenario (mid-sized meal) and an ‘eating out’ scenario (larger meal + alcohol). During overnight closed loop delivery, sensor measurements of glucose were fed into a computer algorithm, which advised insulin pump infusion rates at 15 minute intervals.

For the eating in scenario, overnight closed loop delivery of insulin increased the time plasma glucose levels were in target by 15%. For the eating out scenario, closed loop delivery increased the time plasma glucose levels were in target by 28%. Overall, time plasma in target range increased by 22%, and overnight time spent hypoglycemic was reduced by 3%.

Transplantation of encapsulated stem cells reduces glucose levels in diabetic mice

Insulin producing cells have been derived from stem cells and transplanted into mice with diabetes. Stem cells from human umbilical cord blood and from mouse bone marrow were differentiated into insulin producing cells, and encapsulated in an alginate membrane before being transplanted into diabetic mice.

Transplantation of these cells into mice with diabetes led to reduced blood glucose levels and increased body weight. Encapsulation protected the transplanted cells from the immune response and prevented graft rejection.

Whilst it has long been known that insulin pump therapy can provide both a physical and psychological benefit to users, results from the recent Sensor-Augmented Pump Therapy for A1C Reduction trial (otherwise known as STAR 3) have shown that using an insulin pump in combination with a continuous glucose monitor can significantly reduce blood sugar fluctuations.

Published in the New England Journal of Medicine, results showed that all patients using the sensor-augmented system demonstrated a reduction in mean A1C levels that was four times greater than patients using insulin injections alone. This lower A1C result was sustained throughout the year of the trial.

An important additional result highlighted by the researchers was that the reduction in average blood glucose levels was not associated with an increased incidence of hypoglycemia.

One of the key steps to the development of an effective ‘artificial pancreas’ is the successful pairing of insulin delivery with blood glucose measurement. This research, in combination with the exciting results being obtained by the JDRF Artificial Pancreas Consortium, show that using a combination system enables users to better manage their glucose levels, even when eating, exercising or sleeping. Ultimately this will result in reduction of long-term complications and hypoglycemia and an increase in quality of life.

The Sensor-Augmented Pump Therapy for A1C Reduction trial was sponsored by Medtronic and involved JDRF-funded researchers across the US.

To date, the closed-loop systems tested have combined an insulin pump with glucose monitoring and complex computer programs designed to predict and activate insulin release as required. Whilst results of these trials have been overwhelmingly positive, researchers have found it to be more difficult than first anticipated to finely tune blood glucose levels – particularly when protecting patients against potentially dangerous hypoglycemia caused by too much insulin.

Dr Edward Damiano

This research program, led by Dr Edward Damiano in Boston USA, looked to the healthy pancreas for inspiration and came up with the idea of adding glucagon into the system.

Glucagon is a hormone produced naturally by the healthy pancreas to oppose the effect of insulin – finely tuning glucose levels by releasing the right amount of insulin or glucagon depending on how much glucose is required for the body to function. As most people with type 1 diabetes will know, glucagon is also used in hospitals to remedy hypoglycemic emergencies.

In this trial, the researchers developed a predictive computer program and pump technology that allowed for minute amounts of both insulin and glucagon to be released in response to fluctuating blood glucose. They combined this with intravenous glucose monitoring and tested the system on 11 hospital-based patients with type 1 diabetes.

Whilst the system did require some tweaking to account for unexpected differences in insulin absorption rates, the final results showed that all 11 patients maintained blood glucose levels within the target healthy range throughout the duration of the trial, even after eating high-carbohydrate meals.

Future trials are now planned to investigate the potential for introducing a commercially available continuous glucose monitor and to test the success of the system in patients experiencing realistic life situations such as exercising or illness.

Find out more about the JDRF Artificial Pancreas Project.

Published today in the respected journal The Lancet, JDRF-funded researchers developed and successfully tested an automated management system, which was able to predict and prevent blood sugar fluctuations. Dramatic blood sugar drops, or hypoglycemia, have immediate and often devastating consequences and have an enormous impact on both individuals and families living with type 1 diabetes.

The system being tested in this case combined a commercially available insulin pump and continuous glucose monitor with a sophisticated computer algorithm designed to calculate the appropriate amount of insulin required in different circumstances. It was fitted to participants with type 1 diabetes aged between 5-18yrs who were kept overnight at hospital for monitoring.

The results of the trial showed that the children using the system spent twice as much time in a healthy blood sugar range. A further trial showed that that this protective quality did not diminish when participants consumed a large carbohydrate meal before bed and showed an even more positive improvement when participants did strenuous exercise before bed.

According to the Chief Investigator, Dr Roman Horvorka, these results show that commercially-available devices, when coupled with the newly developed algorithm, can improve glucose control in children and significantly reduce the risk of overnight hypos. This is a significant improvement on current management practices and will ideally be moved into wider clinical testing in the home environment.

Dr Dorota Pawlak

Commenting on the research, JDRF Research Manager Dr Dorota Pawlak said “An automated diabetes management system, or artificial pancreas, is the Holy Grail for people who are living with insulin-dependant diabetes.”

“While an artificial pancreas isn’t a cure, it will help to significantly reduce serious diabetic health complications whilst also reducing the burden on individuals and families that live with the constant fear of blood sugar fluctuations.”

“This trial is the first real proof that existing management technology can be expanded to make a dramatic difference to the lives of people living with type 1 diabetes and also their carers.”

This research project is just one element of JDRF’s global Artificial Pancreas Project which is bringing together the best scientific teams across the world to progress development of the artificial pancreas system as fast as possible.  You can find out more at www.jdrf.org/artificialpancreas

This research is only possible thanks to the generosity of JDRF’s supporters.

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

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