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Mediation Pathways For The Receptor For Advanced Glycation End Products In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$333,812.00
Summary
Excess sugar in the blood from diabetes is detrimental and can accelerate a process where sugar attaches itself to proteins, fats and DNA. Although facilitated by high sugar, the reaction occurs happily in the presence of low sugar with high levels of free oxygen radicals. These complexes are called advanced glycation end products or AGEs. In addition, we ingest vast volumes of AGES from our diet which are taken into the blood. These AGEs are known to be involved in the development of kidney dis ....Excess sugar in the blood from diabetes is detrimental and can accelerate a process where sugar attaches itself to proteins, fats and DNA. Although facilitated by high sugar, the reaction occurs happily in the presence of low sugar with high levels of free oxygen radicals. These complexes are called advanced glycation end products or AGEs. In addition, we ingest vast volumes of AGES from our diet which are taken into the blood. These AGEs are known to be involved in the development of kidney disease in diabetic subjects. AGEs exert most of their effects on the body by binding to specific proteins, the most common and nasty of which is the receptor for advanced glycation end products, RAGE. RAGE is a known participant in other serious diseases such as Alzheimer's disease and evidence is mounting for its central role in the development of kidney disease in diabetic subjects. There is not much known about the processes which mediate RAGE which is why this is the aim of this proposal. This will enable us to stop the relentless progression of kidney disease in diabetes.Read moreRead less
Development And Validation Of A Health Policy Simulation Model For Type 1 Diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$409,199.00
Summary
This proposal brings together an international multi-disciplinary team to develop and validate a health economic computer simulation model for type 1 diabetes and its complications. It examines the impact of diabetes on costs as well as quality of life. Outcomes generated by the model will inform health policy decisions regarding allocation of resources for people with type 1 diabetes such as cost-effectiveness analysis of new treatments and technologies.
Epigenetic Determinants Of Nephropathy In Adults With Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$532,118.00
Summary
The prevention and successful management of diabetic complications are issues of utmost importance for the health of Australians. We hypothesize that epigenetic pathways partly determine why some individuals with diabetes develop complications of their disease, while others do not, despite a similar duration of diabetes, treatment intensity and mean glucose exposure.
JDRF/NHMRC Diabetes Complications Centre Of Research Excellence
Funder
National Health and Medical Research Council
Funding Amount
$2,607,291.00
Summary
Despite intensive intervention some individuals with type 1 diabetes develop complications. There remains an urgent need for means to identify patients at risk of complications and new targets and therapies for preventing, arresting, treating and reversing them. The primary objective of the Diabetes Complications Centre of Research Excellence (DC-CRE) is to translate novel experimental findings into preventive/treatment strategies for the management of diabetes and its complications.
Characterisation Of Novel AGE Binding Proteins: Implications For Diabetic Vascular Complications.
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This i ....This project will explore a process known as advanced glycation and in particular how this may lead to organ injury in diabetes. Diabetes is characterised by sustained elevation of blood glucose levels which interact with proteins to generate products known as advanced glycation end-products (AGEs). These AGEs bind to other proteins some of which have been isolated and are considered receptors. Our own group has identified a new family of proteins known as ERM proteins which bind to AGEs. This is a highly novel finding which now needs to be examined in more detail. The ERM proteins which include ezrin, radixin and moiesin are found at many sites of diabetic complications including the kidney, retina and blood vessel wall. They have a number of functions including effects on cell adhesion and cell structure. This is important in diabetes where changes in cells including altered structure have been observed. This grant will characterise the interactions between AGEs and ERM proteins at the molecular and cellular level. It will define how AGEs influence cells via interactions with ERM proteins. These studies have the potential to lead to treatments that may modulate the AGE-ERM interactions, thereby retarding or preventing diabetic vascular complications. These complications are of important clinical significance since they are the major cause of morbidity and mortality in the diabetic population. Furthermore, diabetes is a major cause of premature atherosclerosis in our community, diabetic kidney disease is the leading cause of end-stage renal failure in the Western world and diabetic retinopathy (eye disease) is the main cause of blindness in the working age population.Read moreRead less
E-PREDICE Early Prevention Of Diabetes Complications In Europe
Funder
National Health and Medical Research Council
Funding Amount
$917,400.00
Summary
The e-PREDICE study will randomise 3000 people aged 45-74 with mild hyperglycaemia or early diabetes to treatment with intensive lifestyle modification alone, or plus metformin, or sitagliptin, or liraglutide, aiming to reduce diabetes eye, kidney and nerve damage. The Australian arm will be co-ordinated by the University of Sydney and other sites include Baker IDI Heart and Diabetes Institute, Royal Melbourne Hospital, St Vincent’s Hospital Melbourne and Royal Brisbane and Womens Hospital
The Role Of The Thioredoxin System In Angiogenesis And Impaired Neovascularisation In Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$306,501.00
Summary
For many sufferers of heart disease who suffer from blocked coronary arteries, current treatments (e.g. bypass surgery or angioplasty) are unable to offer relief from the debilitating effects of occluded arteries. This is particularly true of patients with diabetes who have more aggressive blockages. We plan to study a newly identified mechanism to facilitate growth of new blood vessels to sites affected by vascular disease . Ultimately, this may result in new treatments for heart disease.
Non-invasive Detection Of Hypoglycaemia In People With Diabetes Using Brain Wave Activity
Funder
National Health and Medical Research Council
Funding Amount
$330,447.00
Summary
Hypoglycaemia remains a major cause of morbidity and mortality in people with both type 1 diabetes and type 2 diabetes who require insulin therapy. Current treatments for nocturnal hypoglycaemia are usually ineffective. Combining brain wave recording and artificial intelligence, we will identify the changes that precipitate an episode of hypoglycaemia allowing the development of a non-invasive device to prevent or alleviate these fearful and potentially life-threatening events.
My research focuses on the mechanisms responsible for diabetic kidney and heart complications with an emphasis on identifying novel targets as the basis for developing new treatment to reduce the burden of these complications. It is hypothesised that diabetic complications arise as a result of a number of key factors, the most important being chronic elevation of blood glucose.