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”.

Under healthy conditions, beta cells regenerate slowly to respond to increased insulin requirements or to replace those lost by injury. In the case of type 1 diabetes however, the beta cells are destroyed faster than they can naturally regenerate.

For the last decade, researchers around the world have been working towards developing ways to either re-grow remaining beta cells, or transplant new beta cells that have been genetically modified to be invisible to the immune system.

In this case, the research team led by Dr Pedro Herrera at the University of Geneva in Switzerland, took a slightly different approach. They killed off all functioning beta cells in a special population of mice then gave the mice insulin therapy whilst using fluorescent dyes to track what happened to the cells in their pancreas over the next year.

What they found is that another group of pancreas cells – the alpha cells – spontaneously reprogrammed themselves over time to take over the role of insulin production.

Alpha cells reside next to beta cells in the pancreatic and normally produce glucagon – a hormone that has the opposite effect of insulin. In this case, researchers found that after they were reprogrammed, they produced both glucagon and insulin in quantities sufficient enough to maintain normal blood glucose levels.

Dr Dorota Pawlak

Dr Dorota Pawlak, Head of Research Development for JDRF Australia says that this is an enormously exciting discovery for type 1 diabetes research.

“This research is the first to show that it is possible to spontaneously regenerate insulin-producing cells from other pancreatic tissue without having to resort to complex and potentially dangerous drug treatments.”

“The key difference between this study and others is all the beta cells were removed.”

“It is believed that a small number of beta cells still exist in the pancreas of people with type 1 diabetes, even after many years of living with the disease. This research showed simply removing all the beta cells in mice naturally triggered the re-programming process in the alpha cells.”

“Whilst it is important to remember that this research was conducted in mice and therefore is not immediately transferable to humans, it is a great step forward and will ultimately lead to the development of new therapies to reverse and cure type 1 diabetes.”

JDRF is a world leader in the field of beta cell regeneration. Find out more about beta cell regeneration.

After extensive discussion in Australia and overseas, Australian diabetes health professionals have released a new position statement on blood sugar targets for people with type 1 diabetes. Following the results of the Diabetes Control and Complications trial, the ideal target of a HbA1c of 7% was set across the board.

Recent research has suggested that one size may not fit all and to address this, the Australian Diabetes Society now officially recommends that people with severe hypoglycemia or hypoglycemia unawareness should set their HbA1c targets at 8% or less.

Medical Journal of Australia

Diabetic ketoacidosis still common

Research from Germany has indicated that one in five children diagnosed with type 1 diabetes will suffer severe diabetic ketoacidosis at disease onset – a rate that has remained constant over the last 13 years even though major have been made in diabetes care during that time.

It has been suggested that this may result from a lack of recognition of symptoms by general clinicians. In many cases this leads to a dangerous delay in diagnosis, resulting in an increased risk of complications like ketoacidosis and removing the opportunity to protect remaining insulin-producing cells.

The International Diabetes Federation has called for increased public awareness of the early symptoms of type 1 diabetes leading up to World Diabetes Day on November 14, 2009.

Diabetes Care

Australian researchers discover molecule involved with beta cell death

A JDRF-funded research team from the Walter and Eliza Hall Institute has conclusively identified the role of a molecule suspected of triggering the death of beta cells. Researchers showed that the molecule – called Fas ligand – is present in two different forms.

One protects against autoimmunity and the other, in large concentrations, can increase the risk of autoimmune attack. Researchers are now looking to use this knowledge to create a therapy to slow down the autoimmune attack or prevent type 1 diabetes onset altogether.

Nature

MRI may help physicians diagnose type 1 diabetes

A non-invasive MRI scan may help clinicians to diagnose and identify suitable treatment plans for, type 1 diabetes.

According to researchers at Harvard Medical School, MRI scans can evaluate beta cell mass as well as detect any inflammation of the pancreas. This technique will therefore identify if a person is experiencing the autoimmune process associated with type 1 diabetes, as well as calculating how many functioning beta cells might be left.

Having this information would allow clinicians to prescribe a treatment plan suitable for the disease stage.

JDRF-funded researchers Ms Eliana Mariño and Dr Shane Grey have demonstrated the cells of the human immune system can be manipulated to prevent type 1 diabetes.

The body’s immune cells, or white blood cells, include B cells and T cells. B cells make antibodies and present ‘antigens’ to T cells, allowing them to recognise and kill invaders.

Previous research by the authors has showed that groups of B cells migrate to the pancreas and pancreatic lymph nodes and tell T cells to kill the cells that produce insulin.

Working with mice that spontaneously develop type 1 diabetes, the team used a special molecule called BCMA to block a hormone responsible for controlling the survival of B cells, called BAFF. As the B cells were removed using this technique, a special type of T cell (called regulatory T cells) increased and prevented the autoimmune attack on the pancreatic cells.

They found that after this treatment, none of the mice developed type 1 diabetes – a remarkable finding, as other B cell depletion methods have just delayed or reduced disease incidence.

The molecule BCMA is already being used in clinical trials for other autoimmune diseases, such as Sjogren’s Syndrome and Lupus and this result provides support for the development of a human type 1 diabetes trial.

This work was conducted under the auspices of the Diabetes Vaccine Development Centre (DVDC) at the Garvan Institute of Medical Research in Sydney.

Diabetes published online April 29 2009

Researchers have used a transplant of a patient’s own treated blood cells to increase and preserve beta cell function in young people recently diagnosed with type 1 diabetes.

The research team, from the US and Brazil, hoped that if they intervened early enough they could wipe out and then rebuild the body’s immune system by using stem cells, preserving a reservoir of beta cells and allowing them to regenerate.

They enrolled Brazilian diabetics aged between 14 and 31 who had been diagnosed within the previous six weeks. After stem cells had been harvested from their blood, they underwent a form of chemotherapy to eliminate the white blood cells causing damage to the pancreas. They were then given transfusions of their own stem cells to help rebuild their immune systems.

The trial results indicate that destroying and restarting the immune system may “retrain” or “reset” the immune system without the immune response that caused type 1 diabetes in these patients initially, at least for a period of time.

While the trial seems to provide proof of concept that the autoimmune response that causes diabetes can be overcome by resetting the immune system, there are a number of serious issues that will need to be addressed before this approach can become widely available.

JDRF Australia’s Research Development Manager Dr Dorota Pawlak said that “Stem cells have the science community very excited but there are still significant challenges.”

“Firstly, it is not known whether the treatment represents a “cure” or a temporary resetting of the immune system with an eventual slide back into the autoimmune destruction of the beta cells.”

“Secondly, the results of this study are only relevant to people who are newly diagnosed and may still have some beta cells function left.”

“Finally, and most importantly, the risks and long term side effects associated with this highly invasive treatment need to be better quantified, mitigated, and weighed against the benefits of the procedure.”

“This is a key point – to deliver a cure to people with type 1 diabetes we need stem cells that are pure, safe and that don’t require the use of heavy immunosuppressive drugs. This is especially important for children with type 1 diabetes.”

Dr Pawlak noted that the work complements the number of studies funded by JDRF that use stem cells both as a research tool, and as a potential therapy for type 1 diabetes.

Journal of the American Medical Association 297(14):1568-76.

PhD student Eliana Mariño and Dr Shane Grey, from the Garvan Institute of Medical Research in Sydney, have demonstrated how a particular molecule may be used to prevent type 1 diabetes in the future. Their findings are published online in the international journal Diabetes.

JDRF’s Research Development Manager said this research, part funded by JDRF, is significant. “These results are impressive and they represent a promising step towards a vaccine for type 1 diabetes.”

“Significantly, related compounds have already been approved for clinical trials for other autoimmune diseases such as lupus, so we hope to see clinical trials with humans to prevent type 1 diabetes in around five years time.”

PhD student Eliana Mariño and Dr Shane Grey are pictured here with JDRF Youth Ambassador Brendan Rose.

How it works

White blood cells, the cells of the immune system that defend the body against infectious disease and foreign materials, include B cells and T cells. The B cells make antibodies and present ‘antigens’ to T cells, which help them to recognise, and kill, invaders.

In previously published studies about Type 1 diabetes, Dr Grey’s lab has shown that groups of B cells migrate to the pancreas and pancreatic lymph nodes, presenting specific insulin antigens to T cells. In other words, B cells go to the disease site and tell T cells to kill the cells that produce insulin.

“This study looks at different ways of subduing B cells, and how that affects development of the disease,” said Grey.

Working with mice that are genetically programmed to develop type 1 diabetes (NOD mice), Eliana Mariño found that if she blocked B cells known as BAFF cells, which control cell survival, before the mice developed type 1 diabetes, none of the mice in the study developed the disease.

“This is a remarkable finding, as other B cell depletion methods tested elsewhere have just delayed or reduced disease incidence,” said Eliana.

When B cells were depleted, the regulators of the immune system (a subclass of T cells known as T regulatory cells) rose in numbers.

By removing B cells from the picture for a while, it appears you allow T regulatory cells to function as they should, subduing killer T cells and somehow making them tolerant of the insulin producing cells.

The molecule used by Grey and colleagues to inhibit BAFF is known as BCMA, and is already being used in clinical trials for other autoimmune diseases, such as Sjogren’s Syndrome and Lupus.

Next Steps

The Diabetes Vaccine Development Centre (DVDC), which seeks to develop a vaccine for type 1 diabetes, is funding further research with the compound.

The DVDC is a jointly supported initiative of Australia’s National Health and Medical Research Council and the Juvenile Diabetes Research Foundation International and is administered through the Garvan Institute of Medical Research

TV News

This story was covered by ABC TV. Click on Video to hear YA Brendan Rose and JDRF Research Development Manager Dr Dorota Pawlak discuss this research.

ABOUT GARVAN

The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent’s Hospital in Sydney, it is now one of Australia’s largest medical research institutions with nearly 500 scientists, students and support staff. Garvan’s main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan’s mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan’s discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.

Garvan Institute Media enquiries

Alison Heather, Science Communications Manager, Garvan Institute of Medical Research, 0434 071 326

JDRF Media enquiries

Lyndal Howison, Media and PR Executive, Juvenile Diabetes Research Foundation, 0411 110 717