Stress Hyperglycaemia And Mortality In Critical Illness: Defining The Association And Underlying Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$125,526.00
Summary
The relationship between high blood sugar levels (hyperglycaemia) and mortality in critically ill patients remains an area of controversy with conflicting results between studies. This PhD thesis will attempt to resolve this by firstly evaluating whether relative hyperglycaemia as measured using a novel new measure better predicts mortality outcome in such patients; and secondly, attempt to establish possible mechanisms which contributes to this.
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
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.
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.
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
The Role Of Urotensin II In Diabetes-Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$405,594.00
Summary
People with diabetes most commonly die from stroke or heart attack and we need to determine what makes them more prone to these problems. The recently discovered UII system is increased in people with diabetes and has been found in diseased parts of blood vessels. Thus, the aim of this project is to characterise the UII system in the setting of diabetes using 2 unique genetically altered mice and a blocker a to study the effects of high cholesterol, diabetes and a deletion of UII.
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