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The Role Of The MicroRNA Let 7 In Diabetic Proliferative Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$674,084.00
Summary
Cardiovascular complications remain the major cause of mortality in diabetes and our current treatment strategies are insufficient to reduce this burden. We have obtained extensive data to show that a novel molecule (the micro RNA, let 7b) has antiproliferative and vasculoprotective effects in diabetes. Thus, we propose that modulation of micro RNA let 7b specifically in vascular smooth muscle cells within the vascular wall represents a promising target to combat cardiovascular disease, in parti ....Cardiovascular complications remain the major cause of mortality in diabetes and our current treatment strategies are insufficient to reduce this burden. We have obtained extensive data to show that a novel molecule (the micro RNA, let 7b) has antiproliferative and vasculoprotective effects in diabetes. Thus, we propose that modulation of micro RNA let 7b specifically in vascular smooth muscle cells within the vascular wall represents a promising target to combat cardiovascular disease, in particular in diabetes.Read moreRead less
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 Dicarbonyl-derived AGEs And RAGE In Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$470,617.00
Summary
Based on our pilot data we postulate that glucose derived molecules such as methylglyoxal (MGO) have effects on inflammation and oxidative stress leading to accelerated atherosclerosis in diabetes. Our studies aim to identify novel treatments which block these effects thus leading to superior protection and prevention of atherosclerosis in diabetes.
Biomarkers For Risk And Outcomes Of Type 2 Diabetes: A Discovery And Validation Approach In Australian And Chinese Subjects
Funder
National Health and Medical Research Council
Funding Amount
$599,489.00
Summary
The aim is to make better outcomes for people with Type 2 diabetes in Australia and China, by exploring various tests to improve prediction of diabetes progression, complication risk and treatment response. The team has data and samples from the Fenofibrate Intervention and Event Lowering in Diabetes Trial and from the Shanghai Diabetes Study. This approach is very time and cost-effective. We will also study animal models to understand mechanisms of diabetes damage, and test new treatments.
Role Of Epigenetic Mechanisms In Diabetic Vascular Complications
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
Diabetic complications including heart attacks, strokes, kidney disease and blindness appear to be related to the high glucose (sugar) level but how glucose itself induces end-organ injury remains to be fully determined. In this proposal it is suggested that the long-term damaging effects of glucose relate to its ability to damage the regulation of genes by directly affecting DNA and its covering known as histones. Specifically glucose, possibly by altering certain biochemical pathways called ox ....Diabetic complications including heart attacks, strokes, kidney disease and blindness appear to be related to the high glucose (sugar) level but how glucose itself induces end-organ injury remains to be fully determined. In this proposal it is suggested that the long-term damaging effects of glucose relate to its ability to damage the regulation of genes by directly affecting DNA and its covering known as histones. Specifically glucose, possibly by altering certain biochemical pathways called oxidation pathways, interferes with enzymes which affect the structure of DNA and related molecules resulting in altered expression of many proteins. One of these proteins known as NF kappa B is activated in diabetes, probably by mechanisms involving regulation of these enzymes which play a central role in modifying gene structure. By clarifying the exact mechanisms at a molecular level that mediate the effect of glucose on genes and proteins it will be possible to target these molecules and develop new treatments to prevent, retard or reverse the blood vessel complications that are so common in diabetes.Read moreRead less