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
The role of SGK-1 and SGK-2 in hypertension and nephropathy in diabetes mellitus. The key objective is to define the suitability of the serum glucocorticoid regulated kinases -1 and -2 (SGK-1, -2) as novel drug discovery targets. A specific inhibitor targeting SGK-1 and -2 will be tested to determine if it reverses the enhanced sodium reabsorption and extracellular matrix production characteristic of progressive renal failure in in vitro models models of renal disease. These inhibitors present a ....The role of SGK-1 and SGK-2 in hypertension and nephropathy in diabetes mellitus. The key objective is to define the suitability of the serum glucocorticoid regulated kinases -1 and -2 (SGK-1, -2) as novel drug discovery targets. A specific inhibitor targeting SGK-1 and -2 will be tested to determine if it reverses the enhanced sodium reabsorption and extracellular matrix production characteristic of progressive renal failure in in vitro models models of renal disease. These inhibitors present an opportunity to control hypertension whilst simultaneously limiting fibrosis in the kidney. Renal failure is steadily increasing and is now the single largest health care cost to the community. These studies will provide the proof of concept required to ultimately bring this novel preventative therapy to the community.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
NR1 Nuclear Hormone Receptors, And Skeletal Muscle Metabolism: Insights Into Dyslipidemia And Metabolic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$582,547.00
Summary
The significance of Nuclear hormone receptors (NRs) in disease is underscored by the range of pharmacopoeia for the treatment of NR-associated disorders (e.g 16% of the top 100 drugs target NRs). Orphan NR1 receptors are abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for ~40% of total body weight, and energy expenditure. Muscle is the major site of glucose metabolism and, fatty acid oxidation. Furthermore, it is an important regulator of cholesterol homeost ....The significance of Nuclear hormone receptors (NRs) in disease is underscored by the range of pharmacopoeia for the treatment of NR-associated disorders (e.g 16% of the top 100 drugs target NRs). Orphan NR1 receptors are abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for ~40% of total body weight, and energy expenditure. Muscle is the major site of glucose metabolism and, fatty acid oxidation. Furthermore, it is an important regulator of cholesterol homeostasis and HDL levels. Consequently, it has a significant role in insulin sensitivity, the blood lipid profile, lipid metabolism and obesity. Understanding the functional role of the orphan NR1 receptors in skeletal muscle in the context of inflammation, lipid and energy homeostasis is of paramount importance in further understanding the mechanistic basis of dyslipidemia, chronic inflammation, insulin sensitivity, diabetes and obesity. Identification of novel NR1 targets that regulate metabolism in a major mass peripheral tissue, and positively influence the risk factors for cardiovascular disease, provides platforms for potential therapeutic intervention. Cardiovascular disease is the foremost cause of global mortality, and was responsible for >15 million deaths in 2003.Read moreRead less
ADVANCE-ON: A Post-trial Observational Study Of ADVANCE
Funder
National Health and Medical Research Council
Funding Amount
$775,867.00
Summary
The ADVANCE (Action in Diabetes and Vascular Disease) study demonstrasted that intensive control of blood glucose only reduced kidney disease but that control of blood pressure reduced both cardiovascular and kidney disease. This 10-year post-trial follow up study will determine whether intensive control of blood glucose exerts cardiovascular benefits that emerge in the long term in patients with type 2 diabetes.
Brown fat protects animals against obesity and diabetes. Humans with abundant brown fat are metabolically healthy. Identification of medication that boosts brown fat function may lead to novel treatment of metabolic disorders. This proposal will examine the role of such a medication, which is modeled on a factor (called FGF21) released from brown fat. The project will also search for other factors released by human brown fat, which may become future targets of obesity treatment.
Sex Hormones And Heart Disease In Older Women Study (The SHOW Study)
Funder
National Health and Medical Research Council
Funding Amount
$594,672.00
Summary
Cardiovascular disease (CVD, heart disease and stroke) is the leading cause of death in women aged 65 and over. Counter-intuitively, androgens may be as, or even more important, than estrogens in determining CVD risk and all-cause mortality in women, but this is yet to be verified. We will document blood levels of androgens in women aged 70+ and determine whether androgens are associated with CVD and death in this large cohort of elderly well women.
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