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Prediction Of Adverse Outcomes Following A Fragility Fracture
Funder
National Health and Medical Research Council
Funding Amount
$148,426.00
Summary
Individuals with an existing fracture are at increased risk of adverse outcomes such as re-fracture and premature mortality, but it is not clear why. We propose to evaluate risk factors, and prognostic models, for predicting the risk of adverse outcomes. We also propose to develop a quantitative risk-benefit framework for evaluating the clinical utility of such prognostic models and help ensure that therapies appropriately address real-life experience of osteoporotic patients.
The Regulation Of Aromatase In The Context Of Obesity And Postmenopausal Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$436,601.00
Summary
Current hormone therapy for breast cancer using inhibitors of oestrogen formation results in serious side-effects including bone loss, joint pain and possibly cognitive issues. Our current work is aimed at understanding how oestrogen formation is regulated with the goal of developing breast-specific inhibitors of oestrogen formation to obviate these problems. In addition, this work is aimed at devising therapeutic intervention to break the linkage between obesity and breast cancer.
The Effect Of Antiepileptic Medication On Indices Of Bone Health And Risk Factors For Falls And Fractures
Funder
National Health and Medical Research Council
Funding Amount
$469,605.00
Summary
Epilepsy is a common brain disorder and most patients with epilepsy take anti-epileptic drugs (AEDs) for many years. These patients have high rates of bone fractures, but the reasons are uncertain. Earlier studies identifying an association between AED use and bone disease were performed on institutionalised patients, and more recent studies on outpatient populations have been conflicting. A better understanding of this problem is critical for designing potential preventive measures and treatmen ....Epilepsy is a common brain disorder and most patients with epilepsy take anti-epileptic drugs (AEDs) for many years. These patients have high rates of bone fractures, but the reasons are uncertain. Earlier studies identifying an association between AED use and bone disease were performed on institutionalised patients, and more recent studies on outpatient populations have been conflicting. A better understanding of this problem is critical for designing potential preventive measures and treatments. One important additional mechanism by which AEDs may increase fracture risk is impairment of gait and balance, leading to a high risk of falls. We have novel data demonstrating the power of a Twin and Matched Sibling approach to study this important problem. This study showed that chronic AED use was associated with significant deficits in bone mineral density (BMD), a key predictor of the risk of fractures. The proposed project will ask the following questions: 1. Is BMD and estimated bone strength lower in the bones most at risk for fracture in women and men chronically taking AEDs? 2. Is the loss of bone in measurements over time greater in patients continuing to take AEDs? 3. Is the risk of bone loss greater for certain types of AEDs, and is the risk influenced by length of exposure, age and menopausal status? 4. How does AED treatment lead to reductions in BMD and bone strength? 5. Are measures of muscle strength, gait and balance impaired in patients taking AEDs compared with matched people not taking AEDs? The proposed study will utilise twins and pairs of siblings to investigate the effects of the long-term use of AEDs for epilepsy on measures of bone mass and strength, indices of bone turnover, vitamin D status, calcium regulating hormones, mineral levels, sex hormone levels, and measures of muscle strength, gait and balance function. In addition, a group of patients newly commencing AED treatment for epilepsy will be studied over 2 years.Read moreRead less
A Multi-ethnic Cohort And Intervention Trial To Identify Early Biomarkers For Type 2 Diabetes And Customise Individualized Environments For Disease Prevention
Funder
National Health and Medical Research Council
Funding Amount
$597,376.00
Summary
Diabetes is often called a lifestyle disease, however, large clinical studies have shown that diabetes cannot always be prevented through lifestyle modification. This collaborative study between Shanghai Institutes of Biological Science and Sydney University will identify biomarkers that predict the development of type 2 diabetes. Using this knowledge, the best interventions (including diet, exercise and medications) to improve an individual’s risk profile for type 2 diabetes will be identified.
Investigating The Novel Role Of SEPS1 In The Prevention Of Islet Beta Cell Failure And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$535,804.00
Summary
SEPS1 is an important glucose-regulated protein whose function is to protect tissues from oxidative stress. Inhibition of SEPS1 by hyperglycaemia, is a mechanism for progression of Type 1 and Type 2 diabetes once hyperglycaemia supervenes. The overall aim of the project is to investigate the function of the novel SEPS1, using transgenic and knockout approaches.
Testosterone Intervention For The Prevention Of Diabetes Mellitus In High Risk Men: A Randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$5,054,654.00
Summary
Type 2 diabetes (T2DM) is increasingly common, costly and deadly. Some men at risk of T2DM have low testosterone (T) levels. Our preliminary data suggests that T treatment may prevent the development of T2DM, and improve cardiovascular and sexual function, body composition and bone density, and mood. This remains to be fully tested in a randomized placebo-controlled trial, and this project will do so in a 2-year study of T treatment compared to placebo in men at risk of T2DM participating in a l ....Type 2 diabetes (T2DM) is increasingly common, costly and deadly. Some men at risk of T2DM have low testosterone (T) levels. Our preliminary data suggests that T treatment may prevent the development of T2DM, and improve cardiovascular and sexual function, body composition and bone density, and mood. This remains to be fully tested in a randomized placebo-controlled trial, and this project will do so in a 2-year study of T treatment compared to placebo in men at risk of T2DM participating in a lifestyle program.Read moreRead less
Analysis Of Effect Of Different Treatment Targets On Maternal And Child Health Outcomes In Gestational Diabetes Mellitus (GDM), Review Of Specific Treatments And Development Of Clinical And Biochemical Predictors.
Funder
National Health and Medical Research Council
Funding Amount
$122,686.00
Summary
This research aims to analyse newly proposed treatment targets for Gestational Diabetes Mellitus (GDM) and the effect this will have on maternal and child health outcomes, via comparison of data from two large Australian health services using the traditional and newly proposed critiera. The research will also investigate current effective interventions for GDM, including the impact of early antenatal lifestyle interventions, and formulation of a clinical and biochemical risk prediction model.
An obesity epidemic is evident in first world countries including Australia. Twenty seven percent of men aged 55-64 in this country are obese. Obesity results in increased mortality and morbidity from type 2 diabetes, cardiovascular disease, renal disease and endometrial cancer, among others. Given our flaccid lifestyles, it is imperative that the metabolic processes underlying obesity be fully understood, to allow development of suitable treatment modalities. This proposal seeks to establish an ....An obesity epidemic is evident in first world countries including Australia. Twenty seven percent of men aged 55-64 in this country are obese. Obesity results in increased mortality and morbidity from type 2 diabetes, cardiovascular disease, renal disease and endometrial cancer, among others. Given our flaccid lifestyles, it is imperative that the metabolic processes underlying obesity be fully understood, to allow development of suitable treatment modalities. This proposal seeks to establish an important new element in our understanding of the development of obesity, the transcription factor STAT5. With previous NHMRC support, we developed sophisticated genetically modified mice which lack defined signalling processes initiated by growth hormone, an anti-obesity agent. These studies showed a strong correlation between ability to activate STAT5 and resistance to obesity. There is fragmentary literature evidence to support our hypothesis, which could also explain some of leptins anti-obesity actions. Using mice which lack STAT5, we shall establish a role for STAT5 as an antiobesity agent. The actions of STAT5 are normally blocked by feedback inhibitors referred to as SOCS, discovered by Australians. We shall define which SOCS is the feedback regulator for obesity control, allowing us to develop specific anti-SOCS agents which will act as novel anti-obesity agents.Read moreRead less
Can Vitamin D Prevent Diabetes By Improving Insulin Sensitivity And Secreation In Overweight Humans?
Funder
National Health and Medical Research Council
Funding Amount
$715,371.00
Summary
Vitamin D is mainly produced by the action of sunlight on skin. Low levels of vitamin D are becoming more common, as we work more indoors and avoid the sun and have been associated with type 2 diabetes. In proposed study, healthy overweight people, with low vitamin D, will be given vitamin D for 16 weeks to optimise blood levels of this vitamin. We will examine the changes in sugar metabolism. This study should provide important evidence on how vitamin D protects against diabetes and will suppor ....Vitamin D is mainly produced by the action of sunlight on skin. Low levels of vitamin D are becoming more common, as we work more indoors and avoid the sun and have been associated with type 2 diabetes. In proposed study, healthy overweight people, with low vitamin D, will be given vitamin D for 16 weeks to optimise blood levels of this vitamin. We will examine the changes in sugar metabolism. This study should provide important evidence on how vitamin D protects against diabetes and will support novel approaches to diabetes prevention.Read moreRead less
Identifying Novel Targets To Treat And Prevent Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
Diabetes is the leading cause for kidney failure requiring dialysis or transplantation. Diabetic patients also have a higher risk to suffer from heart attacks, stroke and amputations in particular once kidney damage occurs. Current strategies fail to completely protect patients from complications. My research will uncover knowledge gaps in our understanding of diabetes complications, identify new targets ultimately leading to urgently needed more effective treatments and prevention strategies to ....Diabetes is the leading cause for kidney failure requiring dialysis or transplantation. Diabetic patients also have a higher risk to suffer from heart attacks, stroke and amputations in particular once kidney damage occurs. Current strategies fail to completely protect patients from complications. My research will uncover knowledge gaps in our understanding of diabetes complications, identify new targets ultimately leading to urgently needed more effective treatments and prevention strategies to reduce the burden of disease in diabetes.Read moreRead less