Clinical Modulation Of The Hyperglycaemic Effect Of A 10-second Sprint In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$567,207.00
Summary
Although regular exercise provides a number of health benefits for individuals with Type 1 diabetes, it increases the risk of hypoglycaemia, which if severe can result in convulsion, coma and irreversible brain damages. Recently, we have made the surprising discovery that it is possible to prevent hypoglycaemia if exercise is combined with one or several short sprints. Our goal is to identify some of the clinical factors likely to interfere with the glucoregulatory benefits of sprinting.
Mechanisms Of Hypoglycaemic Damage In Developing Brain- A Protective Role For The Insulin-like Growth Factor System
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children ....The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children with diabetes are also at risk, when their therapy with insulin may at times be excessive, leading to hypoglycaemia and impaired glucose availability for the brain. This proposal is examining at the cellular level the mechanisms involved in loss of brain cells in the face of glucose starvation in these various conditions. We are using several in vitro models where we can grow segments of developing mouse brain or human nerve cells in a dish, compared to studies with mice subjected to low blood glucose (hypoglycemia). After establishing that our laboratory models are representative of the whole animal, we will explore the cellular mechanisms involved in neuronal death following hypoglycaemia, particularly the interaction between the insulin-like growth factor (IGF) and other cell survival genes. We will also examine the possibility that treatment with IGF will reduce the loss of nerves in the brain after an episode of hypoglycemia. This may offer new and effective early treatment for this damaging brain injury in both newborn babies and children with insulin-dependent diabetes.Read moreRead less
The Management Of Women With Type 1 Diabetes During Pregnancy And Breastfeeding.
Funder
National Health and Medical Research Council
Funding Amount
$50,741.00
Summary
Pregnancy in women with type 1 diabetes is associated with increased risks to the mother and baby and lower rates of breastfeeding. There is a relative paucity of published studies concerning the management of these women particularly in late pregnancy, immediately after delivery and during breastfeeding. Through a series of studies this project aims to address these areas of uncertainty and thereby improve the management of these women during these periods.
Free-Living Closed-Loop Insulin Delivery For Patients With Type 1 Diabetes: A Long-term Multi-centre Randomized Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,041,986.00
Summary
Closed loop technology for automating the delivery of insulin to patients with Type 1 diabetes has the potential to improve the lives of many with the disease. Though early prototypes are currently under evaluation in small studies, no studies have yet to date applied the technology in a large scale randomised trial. We propose to undertake such a study in order to demonstrate the utility of this technology and facilitate its eventual routine and widespread use in the community in the future.
Closed-loop Insulin Delivery Compared With Islet Cell Transplantation For Adults With Type 1 Diabetes And Impaired Awareness Of Hypoglycaemia
Funder
National Health and Medical Research Council
Funding Amount
$92,745.00
Summary
Hypoglycaemia in adults with type 1 diabetes is common. Evaluation of therapies – the ‘artificial pancreas’ and islet cell transplantation - is warranted in a cohort with repeated episodes of hypoglycaemia. This proposal will assess whether the ‘artificial pancreas’ and islet cell transplantation, compared with usual insulin therapy, will reduce hypoglycaemia and improve other clinical outcomes over 6 months. This has potential to expand therapies used in current clinical practice.
Gastric Counter-regulation Of Hypoglycaemia: Studies In Health And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$357,193.00
Summary
Insulin injections are often needed to treat diabetes, but they can cause low blood sugar levels (hypoglycaemia), which are usually distressing, and sometimes fatal. The stomach is important in regulating blood sugar; in response to hypoglycaemia, it empties food much more rapidly, allowing carbohydrate to be absorbed faster to normalise blood sugar levels. The proposed studies will explore this important area, in order to develop better ways of preventing and treating hypoglycaemia.
The Involvement Of Bone Cells In The Adverse Side-effects Associated With Therapeutic Glucocorticoid Use
Funder
National Health and Medical Research Council
Funding Amount
$290,032.00
Summary
Long-term use of cortisone (glucocorticoids) often leads to significant health problems such as diabetes and obesity. We have convincing preliminary data suggesting these side effects are, at least in part, mediated via bone cells. Inhibiting cortisone action in these cells, in mice treated with cortisone, results in a significant reduction of the negative side effects of this drug on fuel metabolism (eg glucose and lipid levels). The current aim is to investigate how this pathway is involved in ....Long-term use of cortisone (glucocorticoids) often leads to significant health problems such as diabetes and obesity. We have convincing preliminary data suggesting these side effects are, at least in part, mediated via bone cells. Inhibiting cortisone action in these cells, in mice treated with cortisone, results in a significant reduction of the negative side effects of this drug on fuel metabolism (eg glucose and lipid levels). The current aim is to investigate how this pathway is involved in cortisone-induced obesity and diabetes.Read moreRead less
Antenatal Insulin-like Growth Factor-I And Perinatal Growth, Survival And Function Of The Growth Restricted Fetus.
Funder
National Health and Medical Research Council
Funding Amount
$150,370.00
Summary
Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUG ....Poor growth before birth or intrauterine growth restriction (IUGR), as indicated by being light, short or thin for stage of pregnancy, greatly increases the risk of illness and death before and after birth and in infancy. IUGR has increased risks of asphyxia, poor glucose control, hypothermia, respiratory difficulties, neurological problems and poor immune function, many of which persist. IUGR is one of the most common clinical problems in obstetrics and neonatology, with ~6% of infants born IUGR in Australia in non-Aboriginal communities and between 7 to 17% in Aboriginal communities. Despite these adverse consequences for health of the individual throughout life, we do not currently have any effective therapies to treat IUGR. Small infants are mostly a result of an inadequate supply of oxygen and nutrients before birth, due to an impaired capacity of the mother to acquire these for the placenta to deliver them to the growing fetus or due to poor functioning of the placenta itself. This intrauterine malnutrition not only slows growth, but impairs the development of a range of body functions leading to the increased risk of illness and death in IUGR. Therapies to be used before birth to treat IUGR need to either restore supply of oxygen and nutrients or to promote growth and functional development. We have discovered that administration of a major growth promoting hormone, insulin-like growth factor-I (IGF-I), to the IUGR fetus, which has low levels of IGF-I, increases its growth. This project will therefore determine if directly giving this hormone in the IUGR fetus will restore development as well as growth before birth, improving function and hence survival and health after birth. If successful, the first effective approach to the antenatal treatment of IUGR will have been identified and would provide the essential knowledge for the design of a range of therapies to best restore the abundance of IGF within the IUGR fetus to improve perinatal and later outcomes.Read moreRead less
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.
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