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
Comparison Between AICAR And Exercise-induced Stimulation Of Skeletal Muscle AMP-K On Fat/glucose Metabolism In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$347,036.00
Summary
Background and Rationale: Exercise is important in the life of the diabetic. In well controlled diabetes, the rates of whole body sugar usage and energy production in skeletal muscle (SkM) in response to acute exercise are similar to non-diabetics. However in diabetics, little information is available as to how SkM processes sugar and produces energy during exercise. Insulin controls SkM sugar and energy processing in sedentary subjects. During exercise, these processes are controlled by non-ins ....Background and Rationale: Exercise is important in the life of the diabetic. In well controlled diabetes, the rates of whole body sugar usage and energy production in skeletal muscle (SkM) in response to acute exercise are similar to non-diabetics. However in diabetics, little information is available as to how SkM processes sugar and produces energy during exercise. Insulin controls SkM sugar and energy processing in sedentary subjects. During exercise, these processes are controlled by non-insulin factors. The chemical catalyst AMP activated protein kinase (AMP-K), which has been investigated only in normal exercising rats, is an important alternative regulator of acute sugar processing and energy supply for exercising SkM. No studies of AMP-K activity are available in diabetes. Our studies will focus on i) how important is the stimulation of SkM AMP-K in diabetes to efficient SkM sugar processing and energy production; ii) if the benefits of exercise can be simulated by pharmacological stimulation of AMP-K in sedentary diabetic subjects. We aim to i) compare the metabolic effects of exercise vs pharmacological stimulation of AMP-K in normal and diabetic subjects; ii) define the molecular mechanisms which trigger the AMP-K metabolic responses; iii) determine if the circulating levels of insulin, blood sugar and-or blood fat influence the AMP-K metabolic responses. Likely Outcomes: pharmacological stimulation of AMP-K will improve SkM sugar metabolism, but less so in diabetes. The associated AMP-K stimulation of SkM fat metabolism may blunt the beneficial SkM sugar responses, particularly in diabetes. This information will be used in future drug developments for diabetics which aim to simulate the beneficial AMP-K metabolic effects of exercise.Read moreRead less
A Longitudinal Study Of Nerve Morphology In Diabetic Neuropathy Using Novel Non-invasive Ophthalmic Surrogate Markers
Funder
National Health and Medical Research Council
Funding Amount
$540,372.00
Summary
This research project will use two new ophthalmic instruments - the corneal confocal microscope and non-contact corneal aesthesiometer - to directly monitor changes in corneal nerves and corneal sensitivity, over a 5 year period, in diabetic patients suffering from a painful condition of the arms and legs known as diabetic neuropathy. This study will generate important new information that could allow diabetic doctors to more accurately monitor the progression of the disease.
The Role Of Hypoxia Inducible Factor 1a In Beta-Cell Function And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$362,303.00
Summary
HIF1a is a gene which our preliminary data shows is needed for normal beta-cell function and insulin secretion. When beta-cells cannot release enough insulin, blood sugar levels rise, and diabetes develops. This research plan will look at the effects of deletion of HIF1a and of increasing HIF1a to see how this affects function of beta-cells and - or diabetes development. This work may show that HIF1a is a potential therapeutic target for the treatment of diabetes in humans.
Aldosterone Inhibition And Diabetic Retinopathy: Treatments And Mechanisms Of Action
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
The World Health Organization predicts that by 2030, more than 360 million people will have diabetes. Despite almost all patients developing retinopathy, current treatments do not prevent disease progression. One strategy being evaluated is blockade of a hormone called angiotensin II. We have new evidence that a related system called aldosterone exists in retina and contributes to damage. This project will determine if aldosterone blockade is a potential treatment for diabetic retinopathy.
I am a physiologist and my diabetes research involves a preclinical approach to address the issue of diabetes and its major renal and cardiovascular complications
Prof Cooper’s diabetes research encompasses basic mechanisms through to translational research and major clinical trials in order to address the issue of diabetes and in particular the prevention and management of its major renal and cardiovascular complications.
Development Of New Anti-fibrotic Drugs For Prevention Of Diabetic Nephropathy.
Funder
National Health and Medical Research Council
Funding Amount
$133,800.00
Summary
Diabetic kidney disease is the leading cause of kidney failure in the developed world. Currently there is no treatment that reduces the excessive scarring that leads to kidney failure. This project aims to test whether a series of novel compounds that have been specifically designed to reduce scarring can prevent diabetic kidney disease.