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PEACH Study- Patient Engagement And Coaching For Health: An Intensive Treatment Intervention For Patients With Type 2 Di
Funder
National Health and Medical Research Council
Funding Amount
$499,263.00
Summary
This study uses practice nurses integrated in existing general practice structures to implement telephone coaching for patients with type 2 diabetes (T2D) in a disadvantaged community. This is an evidence based patient empowerment strategy designed to increase patient self-management and engagement with the health care system to improve health outcomes.
In type 1 diabetes the body becomes deficient in insulin production from pancreatic b cells because the immune system mistakenly attacks and destroys b cells as if they were an invading infection. Recurrence of autoimmune destruction of b cells also occurs following transplantation of whole pancreas or islet cells and may occur in the future when other engineered insulin producing cells are transplanted. The focus of this program is to better understand how b cells are killed by the immune syste ....In type 1 diabetes the body becomes deficient in insulin production from pancreatic b cells because the immune system mistakenly attacks and destroys b cells as if they were an invading infection. Recurrence of autoimmune destruction of b cells also occurs following transplantation of whole pancreas or islet cells and may occur in the future when other engineered insulin producing cells are transplanted. The focus of this program is to better understand how b cells are killed by the immune system and to test ways of protecting beta cells from these mechanisms. Because of the inaccessibility of the pancreas to study (particularly biopsy) in humans with diabetes, much of the proposed work will be carried out in b cells derived from non-obese diabetic (NOD) mice, the best available mouse model of type 1 diabetes. It is clear from the literature that a molecule called perforin found in cytoxic T lymphocytes (CTL) is a major, if not the major, mechanism the immune system uses against b cells. For this reason we will try to better understand the interaction between b cells and perforin and ultimately design ways of them from perforin-mediated cell death. It is equally clear that there are other mechanisms besides perforin that can cause b cell death and the program will also address discovery of these mechanisms and new ways to block them. Beta cells in NOD mice will be protected from perforin or other mechanisms by the addition of protective genes or removal of harmful genes using transgenic knockout technology. Addition or removal of genes involved in cell death can be done systematically and each protocol tested using NOD mouse model. The process of cell death that b cell undergo in type 1 diabetes is called apoptosis. Apoptosis is a general mechanism by which cells of all types die. Experts in the biology of apoptosis and perforin are important members of the program, providing the opportunity to translate the latest advances in cell death research to diabetes. This research addresses several of the specific research areas of interest to JDRF. It focuses on the prevention of b cell death in individuals with type 1 diabetes receiving islet transplants. It may be applicable in the future to protection of stem or precursor cells that have been differentiated into b cells or even to devising strategies to prevent the development of diabetes.Read moreRead less
Our work package looks at Control of pathogenic autoimmunity through regulation by the autoimmune regulator gene (AIRE) in thymic epithelial cells� and has a major influence on work package no 1). __ Design of specific tolerogenic peptide therapies based on the identification of tissue-restricted self-antigen epitopes escaping tolerance�, but interacts either directly or indirectly with all other packages
Novel Approaches To Pathogenesis, Diagnosis &treatment Of Autoimmune Diseases Based On New Insights Into Thymus-dependen
Funder
National Health and Medical Research Council
Funding Amount
$1,045,422.00
Summary
An individual relies upon their immune system to protect against invasion by hostile organisms. The system usually works well. Invading agents (the 'non-self') are detected and attacked by the immune system's patrolling killer T cells. These normally beneficial cells are called T cells because they were formed and educated in an organ called the thymus, which kick-starts our immune system in childhood, but falls into inactivity by adolescence. Sometimes the education system in the thymus goes wr ....An individual relies upon their immune system to protect against invasion by hostile organisms. The system usually works well. Invading agents (the 'non-self') are detected and attacked by the immune system's patrolling killer T cells. These normally beneficial cells are called T cells because they were formed and educated in an organ called the thymus, which kick-starts our immune system in childhood, but falls into inactivity by adolescence. Sometimes the education system in the thymus goes wrong and it releases T cells that mistakenly attack 'self' instead of 'non-self'. This causes autoimmune diseases, such as type1 diabetes, multiple sclerosis and rheumatoid arthritis. The Euro-Thymaide project aims to determine why and how self-attacking T cells are mistakenly released from the thymus into the body. Usually such errant T cells are detected and destroyed within the thymus, before they have the opportunity to escape and cause autoimmune diseases. The ultimate objective is to learn about the thymus recognition process and help the immune system detect and destroy faulty T cells that patrol the body, thereby preventing the onset of autoimmune diseases.Read moreRead less
Beta Cell Mass In Type 1 Diabetes Mellitus And Islet Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$3,070,136.00
Summary
This research program will examine the cellular and molecular mechanisms underlying the loss of Beta cell mass and function: During the pathogenesis of Type 1 Diabetes Mellitus (T1D); and Following islet transplantation. Though these processes have traditionally been considered to be purely immune-mediated, it is now clear that the response of the beta cell is critical to the final outcome of the auto-immune process and response to therapeutic interventions. Thus the complex interactions between ....This research program will examine the cellular and molecular mechanisms underlying the loss of Beta cell mass and function: During the pathogenesis of Type 1 Diabetes Mellitus (T1D); and Following islet transplantation. Though these processes have traditionally been considered to be purely immune-mediated, it is now clear that the response of the beta cell is critical to the final outcome of the auto-immune process and response to therapeutic interventions. Thus the complex interactions between the cellular and soluble constituents of the immune system, plus the effects of a deregulated metabolic milieu, are integrated at the beta cell. This in turn activates a series of complex transcriptional programs in the beta cell that together determine the beta cells ultimate functional status and survival. We will use knowledge gained from studying these processes to drive the development of novel therapeutic targets and strategies to improve the success of immune-based and transplantation-based therapies.Read moreRead less
Role Of Heparan Sulfate, Heparanase Inhibitors In The Development And Prevention Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$3,242,772.00
Summary
Our recent studies have shown that a special protein (an enzyme called heparanase) and the special carbohydrate (heparan sulfate or HS) that it degrades, play a previously unrecognised role in the development of Type I diabetes (T1D) in mice. We will explore whether destructive immune cells use heparanase to damage insulin-producing islets and deplete them of HS, resulting in islet cell death and T1D. We will develop new agents to inhibit this damage, prevent T1D and protect islet transplants.
Which Transgenic Pig Will Be Used For Islet Transplantation In Humans?
Funder
National Health and Medical Research Council
Funding Amount
$3,031,083.00
Summary
We propose that xenotransplantation of pig islets will cure Type 1 diabetes. This program will generate genetically modified pigs to overcome the molecular differences between pigs and humans by removing a pig gene and inserting several human genes. In addition, we will add immunosuppressive genes and so minimise the need for drug treatment of the diabetic recipient. We will test our hypothesis by transplanting islets from these genetically modified pigs into baboons. We suggest that this will p ....We propose that xenotransplantation of pig islets will cure Type 1 diabetes. This program will generate genetically modified pigs to overcome the molecular differences between pigs and humans by removing a pig gene and inserting several human genes. In addition, we will add immunosuppressive genes and so minimise the need for drug treatment of the diabetic recipient. We will test our hypothesis by transplanting islets from these genetically modified pigs into baboons. We suggest that this will provide an inexhaustible supply of islets for transplantation.Read moreRead less
Hypoglycaemia In Young Patients With Type 1 Diabetes: Pathophysiology, Predisposition And Preventive Strategies
Funder
National Health and Medical Research Council
Funding Amount
$2,680,000.00
Summary
The vision of this proposal is to bring together an active team of experienced investigators that will address important clinical problems affecting the management of children and adolescents with type 1 diabetes. Along with facilities and resources already under development, the program will further establish a core of investigators dedicated to patient centred and clinical research that will facilitate scientific advances to be put into practice. The incidence of type 1 diabetes is continuing ....The vision of this proposal is to bring together an active team of experienced investigators that will address important clinical problems affecting the management of children and adolescents with type 1 diabetes. Along with facilities and resources already under development, the program will further establish a core of investigators dedicated to patient centred and clinical research that will facilitate scientific advances to be put into practice. The incidence of type 1 diabetes is continuing to increase particularly in the young. As we enter the 21st century, insulin treatment aimed at restoring blood glucose levels as close to the normal as possible remains the most effective way to prevent the devastating long-term complications of the disease. Unfortunately this is difficult to achieve largely because insulin therapy is frequently associated with the development of low blood glucose or hypoglycaemia. Hyperglycaemia results in unpleasant symptoms if mild but if severe it can produce convulsions or unconsciousness. The fear of hypoglycaemia is ever present for the patient and their family, this not only significantly impairs quality of life but importantly also severely restricts attempts to control diabetes. One of the major goals of this research program will be to address important unanswered questions related to the development of hyperglycaemia in children and adolescents with diabetes. The research team will examine in detail the protective physiological mechanisms against hyperglycaemia that are deranged in diabetes, they will also study more closely those situations that are known to predispose to hyperglycaemia such as sleep and exercise as well as how the brain is affected as blood glucose falls. By taking this approach we hope to be able to devise management strategies that will lessen the impact of hyperglycaemia in diabetes treatment. It is anticipated that this in turn will contribute to the prevention of diabetes complications as well as reduce the burden of the disease for the patient and his or her family. A second goal of this research program will be to develop an internationally unique resource that will be available to all diabetes investigators. We will build on an already established population based database of all the children and adolescents with diabetes in Western Australia as well as complete a DNA bank of these patients and their families. Thus in addition to bringing together an effective team of researchers, this program will further develop resources that can be central to addressing other important questions related to the causes of diabetes and its complications.Read moreRead less