Reducing CVD Risk In The Metabolic Syndrome And Type 2 Diabetes: Novel Approaches To Studies Of Lipoprotein Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$548,669.00
Summary
The incidence of obesity and diabetes is increasing in Australia. With these two conditions comes an increase in cardiovascular disease risk. Elevated blood lipids are an important component of this increased. Weight loss and cholesterol lowering drugs are first line therapies for obesity and diabetes, respectively. Niacin is effective at lowering lipids and raising HDL cholesterol, but the mechanisms responsible for these changes have not been determined.
Factors Controlling Lipid Accumulation In Non-adipose Tissues
Funder
National Health and Medical Research Council
Funding Amount
$463,500.00
Summary
The fat cells of the body are designed to store excess fuel for use when supply from the diet is low, or in situations like exercise, demand is high. Fat also accumulates to some extent in the cells of other tissues types, but in some people the accumulation is excessive. This can have a number of serious effects. In the liver and muscle it can interfere with the ability of insulin to properly regulate the amount of glucose present in the blood, contributing to the development of diabetes. In th ....The fat cells of the body are designed to store excess fuel for use when supply from the diet is low, or in situations like exercise, demand is high. Fat also accumulates to some extent in the cells of other tissues types, but in some people the accumulation is excessive. This can have a number of serious effects. In the liver and muscle it can interfere with the ability of insulin to properly regulate the amount of glucose present in the blood, contributing to the development of diabetes. In the liver, fat accumulation can also lead to cirrhosis and liver failure. Cardiovascular complications, resulting in premature death, are also likely. However despite these devastating consequences it is not clear what the underlying cause of the over-accumulation of fat is not known. In this project we will investigate in detail several aspects of fat metabolism that we think are important in controlling how tissues take up fat from the circulation and whether it is subsequently stored or burnt for energy. We will study the amount of fat that is taken up by different tissues of the body under a range of conditions including fed, and short- and long-term fasting. We will also use drugs to inhibit or promote the amount of fat that is burnt, to see if this changes the rate at which fat is taken up by different tissues. In addition we will accelerate, by genetic manipulation, the rate at which some key enzymes of fat metabolism are produced, to determine their effect on the amount of fat that is stored by different tissue types. Our aim is to determine the metabolic processes that influence fat accumulation in those adversely affected tissues such as liver, heart and skeletal muscle. The identification of the most important processes will contribute significantly to the targeting of therapies aimed at preventing excess fat accumulation and its associated diseases.Read moreRead less
The first kernels of cardiovascular disease begin very early in life; in the womb and early infancy. These early indications are known to track into adulthood, eventually resulting in diseases such as heart attacks. Dr Huang has found that childhood obesity, high blood pressure, cholesterol and a "prediabetes" profile, cluster together and additionally are associated with many factors in the womb and first few years of life. She investigates how to give babies the optimal healthy start.
Early Retinal Vessel Changes In Diabetes And The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$212,500.00
Summary
Diabetes mellitus affects a large proportion of adult Australians. Furthermore, many non-diabetic Australians are at high risk of developing diabetes (e.g., people with lesser glucose abnormalities, and those who are obese, have high blood pressure, or have high lipid levels). It has been suggested that diseases affecting small blood vessels (microvascular disease) in the body is closely related to the development of both diabetes and the pre-diabetes state. The current study will examine the re ....Diabetes mellitus affects a large proportion of adult Australians. Furthermore, many non-diabetic Australians are at high risk of developing diabetes (e.g., people with lesser glucose abnormalities, and those who are obese, have high blood pressure, or have high lipid levels). It has been suggested that diseases affecting small blood vessels (microvascular disease) in the body is closely related to the development of both diabetes and the pre-diabetes state. The current study will examine the relationship of microvascular disease in the retina (at the back of the eye) to diabetes, pre-diabetes status and diabetes complications. We will use a computer-imaging technique to measure the diameters of retinal blood vessel from digital photographs taken in 2,177 participants of the 1999-2000 Australian Diabetes, Obesity and Lifestyle (AusDiab) Study, a community-based survey of people aged 25 years and older examining risk factors and complications of diabetes. In the proposed study, we aim to answer the following questions: 1) Are changes in the retinal blood vessel diameter (e.g., narrowed or dilated vessels) associated with diabetes and pre-diabetes? 2) Are these retinal vessel changes related to obesity, high blood pressure and high lipid levels? 3) Are retinal vessel changes related to diabetes complications, such as heart disease, kidney disease, nerve problems and foot ulcers? 4) Do retinal vessel diameter changes predict people who will subsequently develop diabetes, irrespective of their risk factor profile? Using this well-characterized population, and existing digital retinal photographs, the proposed study will offer a unique and cost-effective opportunity to address important gaps in our understanding of how diabetes and pre-diabetes develop, and whether they are related to microvascular diseases. This may ultimately lead to new treatment and preventive approaches targeted at the small blood vessels in the body.Read moreRead less
Metabolic Syndrome, Inflammation And Non-alcoholic Fatty Liver Disease In Busselton
Funder
National Health and Medical Research Council
Funding Amount
$351,300.00
Summary
The metabolic syndrome is a clustering of obesity, insulin resistance, high cholesterol and high blood pressure. It could affect up to 30% of the population and often leads to diabetes and heart disease. Fatty liver disease is a chronic liver condition that often has no symptoms but can lead to serious liver damage. It could affect up to 25% of the population and is common even in people who drink very little alcohol. The rising prevalence of obesity in Australia suggests that the metabolic synd ....The metabolic syndrome is a clustering of obesity, insulin resistance, high cholesterol and high blood pressure. It could affect up to 30% of the population and often leads to diabetes and heart disease. Fatty liver disease is a chronic liver condition that often has no symptoms but can lead to serious liver damage. It could affect up to 25% of the population and is common even in people who drink very little alcohol. The rising prevalence of obesity in Australia suggests that the metabolic syndrome and fatty liver disease may be on the increase and therefore so too could diabetes and heart disease which already consume significant health resources. Using the unique health data collection of the Busselton Health Study in Western Australia, this project will help to determine how common these conditions are in Australia and lead to a better understanding of the nature and causes of these conditions including the possible role of chronic inflammation. This important information will be used to provide opportunities for better risk assessment, disease prevention, and earlier intervention.Read moreRead less
Liver Cell Transplantation For The Treatment Of Liver Based Metabolic Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$444,143.00
Summary
We propose to investigate the role of liver cell transplantation (LCT) for the therapy of inherited liver-based metabolic diseases using a methylmalonic aciduria (MMA) mouse model. LCT provides an exciting alternative to whole organ transplantation. Initially it was considered liver cells would be immunopriviledged. This has not proven to be the case. Immune modulation will be important. We will also examine immune modulation using antibodies to optimise longterm survival of allogeneic cells.
Are Large Joint Osteoarthritis And Low Back Pain Metabolic Disorders?
Funder
National Health and Medical Research Council
Funding Amount
$381,972.00
Summary
While osteoarthritis (OA) is considered a “wear and tear” disease, there is evidence that OA may be related to a cluster of metabolic abnormalities including obesity, diabetes mellitus, hypertension and high cholesterol. Similarly, low back pain main be linked to a sedentary lifestyle and metabolic changes. This project will examine the relationship between metabolic derangements and back pain and large joint OA in an attempt to better understand these diseases and develop effective treatments.
The Role Of Metabolic And Inflammatory Factors In Cognitive Decline And Cerebrovascular Pathology In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$945,987.00
Summary
Metabolic factors and measures of inflammation in the body have recently been shown to influence mental function and increase the risk of developing age-related disorders such as Alzheimer’s disease. The influence metabolic factors and inflammation have on function of the ageing brain is likely to be determined by complex interplay between many factors, such as physical health, lifestyle, nutrition and our genes. By studying these factors and how they relate to one another in large groups of eld ....Metabolic factors and measures of inflammation in the body have recently been shown to influence mental function and increase the risk of developing age-related disorders such as Alzheimer’s disease. The influence metabolic factors and inflammation have on function of the ageing brain is likely to be determined by complex interplay between many factors, such as physical health, lifestyle, nutrition and our genes. By studying these factors and how they relate to one another in large groups of elderly individuals, we will be able to determine the role these factors play in brain ageing. In addition we will be able to determine an ‘at risk’ profile for elderly individuals for accelerated ageing effects. Identification of this profile is important as it will allow the development of interventions which may prevent or delay the onset of cognitive decline in late life. We plan to study the impact of metabolic and inflammatory factors on brain ageing and in two groups of elderly individuals both of which are currently being studied in detail by our research team. By using these existing groups we will minimize the costs associated with our research, but maximize the research benefit and the benefit to society. Our groups include a large community sample of elderly individuals aged 70-90 years and a large group of elderly twins aged over 65 years. Our use of twins for the study is particularly important as it will help us separate genetic and environmental influences on the measures. We will measure multiple metabolic and inflammatory factors in the body and determine their relationship to detailed tests of cognitive function and to cerebrovascular pathology on brain magnetic resonance imaging. We will look at how these factors relate to one another and which factors are most strongly associated with accelerated ageing. We will be able to follow subjects in each group over a 2 year interval to see which factors most strongly predict change in cognitive function and cerebrovascular pathology over time. Our research is unique in its inclusion of multiple factors which may affect brain ageing, its ability to look in detail at the contribution of genetic influences on metabolic and inflammatory factors, and in our planned follow-up of these individuals.Read moreRead less