The Effect Of Androgen Replacement Therapy On Bone And Muscle Health In Men With Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
Low testosterone (T) levels are common in men with poor kidney function. Low T is known to cause reduced energy, decreased strength and low libido. Normal T is also needed for healthy bones and muscles. Men with kidney disease are already at risk of fractures, poor strength and quality of life. However, there are few studies that look at replacing T to men with kidney failure. We will investigate how low T affects bone and muscle and assess how giving T can benefit bone, muscle and function.
I am a clinician scientist and nephrologist. My research involves preclinical and clinical translational approaches to identify new targets and develop novel treatments to prevent, reverse and retard the development and progression of diabetic complications.
Fenofibrate And Microvascular Events In Type 1 Diabetes (FAME 1) Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,883,529.00
Summary
Diabetes is one of the commonest cause of blindness in adults. Vision loss, which is irreversible, is a most feared complication of diabetes. A blood fat lowering drug called fenofibrate, available in Australia, has been shown to reduce eye damage in people with Type 2 diabetes by 35-40%, and to prevent eye damage in Type 1 diabetic animal models. This study will evaluate the potential benefits of fenofibrate in 450 adults with Type 1 diabetes who have early diabetic eye damage.
The Role Of Specific Nox Isoforms In Diabetic Renal Disease And Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$460,396.00
Summary
Diabetes is increasing worldwide and in Australia. The majority of patients with diabetes eventually will develop kidney disease and will die of blood vessel complications such as heart attacks and stroke. Oxidative stress (the generation of free oxygen radicals that react quickly with other proteins in the body causing tissue damage) has been suggested to play an important role in kidney and blood vessel disease observed in diabetic patients. This proposal will try to identify and measure speci ....Diabetes is increasing worldwide and in Australia. The majority of patients with diabetes eventually will develop kidney disease and will die of blood vessel complications such as heart attacks and stroke. Oxidative stress (the generation of free oxygen radicals that react quickly with other proteins in the body causing tissue damage) has been suggested to play an important role in kidney and blood vessel disease observed in diabetic patients. This proposal will try to identify and measure specific proteins in the kidney and vessels that are involved in the production of oxidative stress. We aim to define which one of these proteins is the most important. We will assess in detail how these proteins work and which other factors are activated leading to tissue damage. The ultimate goal of these studies is to find new treatment options to decrease the production of harmful molecules in the kidney and blood vessel wall thereby reducing kidney failure, heart attacks, stroke and gangrene in diabetes. In our studies, we will use medications already used in patients to treat high blood pressure in diabetes. In preliminary studies we have shown that these drugs also reduce oxidative stress. Furthermore, we will use novel, more specific treatments that the harmful ptoteins. Through a collaboration with Professor Harald Schmidt and his group from Germany who have recently moved to Monash University in Melbourne we will have access to mice in which specific genes for harmful proteins have been knocked out. These mice when made diabetic will most likely develop less or no kidney and blood vessel damage. Our studies will help to identify the most important oxidative stress producing protein associated with kidney and vessel disease. This knowledge will lead to more effective and more potent treatments for patients with diabetes to prevent, stop or even improve kidney and blood vessel disease thereby reducing disability and death in this high risk group of patients.Read moreRead less
Understanding Vasoactive Hormone Pathways In Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$453,750.00
Summary
High blood pressure damages tissues. In clinical practice blood pressure is measured in large arteries, such as the brachial artery in the arm. However, it is the pressure within the organ such as the kidney that actually causes the damage. In particular, the sieving apparatus of the kidney (called the glomerulus), is especially sensitive to the effects of pressure. In diabetes, the pressure within the glomerulus is high because its outflow valve (called the efferent arteriole) is tightly constr ....High blood pressure damages tissues. In clinical practice blood pressure is measured in large arteries, such as the brachial artery in the arm. However, it is the pressure within the organ such as the kidney that actually causes the damage. In particular, the sieving apparatus of the kidney (called the glomerulus), is especially sensitive to the effects of pressure. In diabetes, the pressure within the glomerulus is high because its outflow valve (called the efferent arteriole) is tightly constricted. Therefore even if blood pressure is thought to be normal when measured in the arm, it may still be excessively high within the kidney. Studies have already shown that lowering within-kidney pressure may have a major impact on the progression of kidney disease in diabetes. However, to date this reduction of within-kidney pressure has been sub-maximal. The planned studies will involve the use of new compounds which have more powerful effects in reducing the formation or action of hormones which promote constriction of vessels in the kidney leading to elevated pressure within the kidney. Furthermore, some of these very new agents can open up or dilate these kidney vessels thereby achieving excellent reductions in the pressure inside the kidney. The proposed studies aim to examine new strategies for preferentially lowering pressure within the kidney down to these ideal levels. These hormones also have other effects which could be relevant to non-kidney sites of injury in diabetes including blood vessels and the retina.Read moreRead less
Obesity And Its Metabolic Associations In Relation To Bariatric Surgery And Maternal-fetal Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
My research will examine the effects of maternal obesity, diabetes and smoking on outcomes evidence at birth in the offspring. Bariatric surgery is the most effective means to achieve sustained weight loss in obese patients and may improve metabolic abnormalities and complications. My research will explore the benefits of bariatric surgery in obese patients with type 2 diabetes with or without the addition of a glucose-like peptite-1 (GLP-1) agonist, liraglutide.
Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their ....Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their etiology, both forms result in an inability of the body to control blood sugar levels. Beta cells release the hormone insulin, which regulates blood sugar levels. Current knowledge suggests that a loss of beta cell mass is important for both diseases. For type I diabetes the beta cells are destroyed by the immune system. Though for type 2 diabetes the causes are less clear, it is apparent that the beta cells are dying. Our research is focused on understanding the molecular pathways that control beta cell survival and regulate their death. Such knowledge would help us understand the complex processes leading to the development of diabetes. Furthermore, we could use this knowledge in the design of genetic engineering strategies to create 'death-defying' beta cells, as a potential therapeutic strategy for the treatment of diabetes.Read moreRead less
Androgen Receptor Signalling In Development And Progression Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$753,420.00
Summary
Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because pr ....Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because prostate cells are dependent on testicular androgens for their growth and survival, surgical or medical castration results in an initial tumour regression. However, tumours inevitably develop resistance to androgen ablation therapy and regrow. In this study we aim to provide the most comprehensive analysis to date of the role of androgen signalling in the initiation and progression of prostate cancer. This will enable us to identify the most effective means of eliminating androgen-dependent prostate tumours and identify tumours with high metastatic potential. Our studies will indicate whether treatments targeting androgen signalling are a more effective strategy to inhibit prostate cancer growth while minimising undesirable side effects.Read moreRead less
Role And Mechanism Of Connective Tissue Growth Factor In Diabetic Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$382,820.00
Summary
Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen pa ....Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen patient outcomes. We have generated data in experimental diabetes in rodents that strongly implicates a heart growth factor in causing diabetic cardiomyopathy. This protein, called connective tissue growth factor (CTGF), is increased in diabetic cardiomyopathy, and is elevated by high glucose and other factors in diabetes. We have published data showing that CTGF causes tissue scarring like that which occurs in cardiomyopathy, by affecting signals in cells called fibroblasts. It increases the laying down of extracellular matrix (ECM) and also inhibits the degradation of ECM by the proteins that break down matrix, known as the MMPand PAI systems. Such accumulation of ECM is thought to be a major factor leading to abnormal muscle function in cardiomyopathy. We now plan to block CTGF in this diabetic heart model to determine if we can prevent diabetic cardiomyopathy. We have generated two methods to inhibit CTGF in the animal model. Echocardiography (a heart ultrasound test), and molecular analysis of the heart tissue will determine if we can prevent the otherwise adverse functional and structural changes of diabetes in the heart. We will also study our baboon model of diabetes to determine if diabetic cardiomyopathy with increased heart CTGF is present in the primates. Cell culture studies from rat heart fibroblasts and myocytes will determine how CTGF has the effect on cells to cause cardiomyopathy and how we might further prevent this condition developing in diabetes.Read moreRead less