Type 1 diabetes develops when the cells that make insulin (pancreatic beta islet cells) are destroyed by the body’s own immune system; it is an autoimmune disease. We don’t know why this happens, but there are a number of theories. By studying the patterns of inheritance of the condition within families, scientists have recently begun to identify gene mutations that increase the chances of the disease developing. Their next step will be to determine how these changes cause the body’s immune system to turn on itself. This can be done by using specially bred strains of mice that carry the same gene mutations.
The main symptoms of diabetes are:
•excessive thirst
•frequent urination, especially at night
•hunger
•weight loss
•fatigue, tiredness and nausea
•visual disturbances, such as blurred vision

Untreated diabetes can severely damage many systems, organs and tissues of the body. Yet even with insulin treatment, a lifetime of diabetes can result in serious long-term consequences, such as damage to eyesight (diabetic retinopathy).

Because type 1 diabetes is caused by an abnormal immune response, it is very different from the other form of diabetes, called type 2 diabetes. Both types of diabetes are caused by an interaction between our environment and our genes, but in type 2 diabetes the beta islet cells don’t die. Instead, they lose the ability to release insulin in response to glucose, and the insulin they do make doesn’t control blood sugar.

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At this stage nothing can be done to prevent or completely cure type 1 diabetes, but the condition can be successfully managed by monitoring blood sugar levels and administering regular insulin injections. Eating certain foods such as beans and fruit, which take longer to be absorbed by the body, may also help. Regular medical checks, including eye tests, are recommended.

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Garvan has several teams of scientists who research type 1 diabetes. They focus on understanding how and why an immune system decides to destroy its insulin-producing beta islet cells, and on trying to create new beta islet cells from other cell types, which could then be used to replace those lost in people with diabetes.

One aim of the Garvan scientists is to identify potential points in the disease pathway at which to intervene and prevent the development of type 1 diabetes. One of the studies has led to the discovery of key factors that control the immune attack on the insulin-producing cells. The next stage is to make or find compounds to block these factors in the hope that they will prevent type 1 diabetes.

Garvan researchers and clinicians are also part of a nationwide program to improve the efficacy of a potential cure, called islet cell transplantation. The Australian Federal Government is funding the program via the Juvenile Diabetes Research Foundation. The program will help take islet transplants from being an experimental procedure to a viable clinical option for people with diabetes.

Transplantation of pancreatic islet cells was first trialled as a therapy for type 1 diabetes in the 1980s, but was not successful until 2000 and, as with other tissue transplants, patients must take anti-rejection drugs for the rest of their lifetime.

Dr Shane Grey heads a group that focuses on understanding how and why the immune system starts to attack the beta islet cells in the pancreas. In the islet cell transplantation program (ITP), his team’s role is to develop tests to monitor the recipient’s immune system for signs of rejection and to monitor genetic changes in the islet transplant. This is one of four projects that fall under the ITP consortium’s umbrella. Shane is also working with Jenny Gunton to find molecular markers to predict, before transplantation, how the islets will function after transplantation – that is, to identify a molecular signature for a successful graft.

Jenny is the Australian Diabetes Society Council representative on the ITP oversight committee. At Garvan, her team are examining the factors that regulate gene expression in beta islet cells. They want to understand which genes are misregulated in type 1 diabetes and the effect this misregulation has on disease onset and progression. Jenny is also involved in the clinical arm of the islet transplant program.

Dr Cecile King is another Garvan researcher whose work will help in understanding and treating type I diabetes. The main aim of Cecile’s group is to identify specific molecules that could be targets for suppressing the T immune cells (also called T lymphocytes) that have an essential role in causing type 1 diabetes. They have found that the T cells that cause diabetes carry molecular markers that allow us to track their development to the gut. These T cells become activated and can infiltrate and damage beta islet cells in the nearby pancreas.

Dr Pablo Silveira brings another line of expertise to Garvan’s diabetes research. His group is working on the B immune cells (also called B lymphocytes) that produce antibodies against the beta islet cells. Their recent research has demonstrated that the B lymphocytes contribute to disease mainly through their unique ability to specifically present beta islet cell proteins to the T cells. After this interaction, the T cells become armed to recognise and destroy the beta islet cells. Pablo’s team want to understand why the B cells that recognise the body’s own tissue aren’t eliminated, as they would be in healthy humans.

In other studies, Garvan scientists have identified an unusual period of intense immune system activation, which occurs before the onset of diabetes. Using a new drug to target the immune system at this time, they can prevent diabetes in laboratory animals raised to show the same pre-onset activation. This drug is now being prepared for phase I clinical trials for the treatment of diabetes in people. Probing the causes and mechanisms that lead to type 1 diabetes will eventually lead us to the discovery of new treatments for this disease.

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