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
Constitutive Activation Of The Growth Hormone Receptor
Funder
National Health and Medical Research Council
Funding Amount
$566,277.00
Summary
Growth hormone regulates growth, metabolism, bone, stem cells and longevity, and cancer. These actions are mediated by the GH receptor, and here we seek to understand how it is activated by the hormone through receptor constructs which are active without hormone, to different degrees. We will use these to elucidate its signaling properties, its ability to promote cancer, to grow muscle, and whether cases of giantism and cancer are a consequence of the activating mutations we have identified.
Activin Type II Receptor Antagonists: Mechanism Of Action And Biological Applications
Funder
National Health and Medical Research Council
Funding Amount
$507,270.00
Summary
Activin is a member of the TGF- family of growth and differentiation factors. Over-expression in mice leads to muscle and liver wasting, scarring during wound healing, disturbances to the reproductive system and various endocrine disorders. Activin's biological activity is promoted by its binding in series to two receptors termed Type I and II. Previous studies by this investigator have shown that selective modification of activin's protein structure can result in activin forms (in this instance ....Activin is a member of the TGF- family of growth and differentiation factors. Over-expression in mice leads to muscle and liver wasting, scarring during wound healing, disturbances to the reproductive system and various endocrine disorders. Activin's biological activity is promoted by its binding in series to two receptors termed Type I and II. Previous studies by this investigator have shown that selective modification of activin's protein structure can result in activin forms (in this instance called activin-M108A) which bind to Type II receptors but fail to promote binding to the Type I receptor. This has led to the hypothesis that activin-M108A may compete for native activin binding to Type II receptors and thus prevent activin's recruitment of the Type I receptor with the consequence that activin's biological activity is inhibited. It is proposed to test this hypothesis by producing sufficient amounts of activin-M108A and testing its inhibitory effects in several mouse models of liver damage, muscular degeneration and ovarian and testicular disease. If activin-M108A, or related modified forms of activin, decrease the morbidity and mortality associated with these murine diseases, then we envisage that these activin type II receptor antagonists will also be beneficial for the treatment of related human conditions.Read moreRead less
Intervention To Reduce The Risk Of Diabetic Retinopathy And Early Adverse Retinal Changes In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,294,846.00
Summary
The long term effects of young onset T1D may be devastating: diabetes is the leading cause of visual loss in young adults in Australia and other countries. We have the unique opportunity to investigate whether ACEI and statins will modify retinopathy through our collaboration with an already funded international multicentre trial. This study will treat adolescents for 4 years and will follow them for the next 5-10 years. We will use novel measures of retinal blood vessels size and fractals.