A team of researchers from Yale University in the US have leant further support to this hypothesis by demonstrating that a certain strain of research mice were far more likely to develop type 1 diabetes when raised in a special germ-free environment as opposed to normal laboratory conditions.

It appears that the mice in the germ-free environment were more susceptible because they had not been exposed to a type of harmless bacteria that lives in the human intestine and commonly found on non-sterile services. Previous research into other disorders has shown there to be interactions between intestinal microbes and the immune system and this research suggests that these interactions may be behind why some people develop type 1 diabetes and others do not.

Whilst the US research suggests that exposure to germs is good for us, JDRF-funded researchers in the UK have revealed a very different result. A recent discovery by scientists based in Brighton has found a definitive link between the incidence of type 1 diabetes and infection with common tummy bugs known as enteroviruses.

Researchers examined the pancreas tissue of people who had passed away not long after being diagnosed with type 1 diabetes and compared it with non-diabetic pancreata. They found that the beta cells found in more than half of the diabetic pancreases were infected with enteroviruses. Conversely, enteroviral infection was rare in the non-diabetic pancreas.

In most people, infection by an enterovirus results in symptoms similar to the common cold or gastric upset. This research suggests that it may also be playing a role in the autoimmune process whereby the immune system labels beta cells as ‘foreign’, resulting in type 1 diabetes.

Both these exciting research breakthroughs have given us a significantly greater understanding of what can trigger the onset of type 1 diabetes and may possibly lead to the development of a therapy or vaccine to prevent the condition.

Nature 455(7216):1109-13
Diabetologia 52(6):1143-51

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