Epigenetic Determinants Of Nephropathy In Adults With Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$532,118.00
Summary
The prevention and successful management of diabetic complications are issues of utmost importance for the health of Australians. We hypothesize that epigenetic pathways partly determine why some individuals with diabetes develop complications of their disease, while others do not, despite a similar duration of diabetes, treatment intensity and mean glucose exposure.
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.
Role Of Circulating Advanced Glycation End Products (AGEs) In Diabetic Nephropathy: Effect Of Benfotiamine Intervention
Funder
National Health and Medical Research Council
Funding Amount
$465,000.00
Summary
Advanced glycation products (AGEs) are compounds formed by the addition of sugars to amino acids (the building blocks of proteins). The addition of sugars to proteins induces biological changes that have been implicated in the development of diabetic complications, especially diabetic kidney disease. AGEs are a diverse group of compounds and to date the exact role that specific AGEs play in the causation of diabetic kidney disease is still unclear. However, new methods are now available that all ....Advanced glycation products (AGEs) are compounds formed by the addition of sugars to amino acids (the building blocks of proteins). The addition of sugars to proteins induces biological changes that have been implicated in the development of diabetic complications, especially diabetic kidney disease. AGEs are a diverse group of compounds and to date the exact role that specific AGEs play in the causation of diabetic kidney disease is still unclear. However, new methods are now available that allow the comprehensive quantification of individual AGE levels in blood. Our study involves the comparison of AGE blood levels, as a group or as specific AGEs with markers of diabetic kidney disease such as albumin (protein) excretion in the urine and the rate that the kidney filters the blood to form urine (glomerular filtration rate). Benfotiamine is a thiamine (vitamin B1) derivative that has been shown to decrease the formation of AGEs and to prevent kidney disease in diabetic animals. The present clinical study will assess whether benfotiamine has similar effects on AGEs and kidney disease in patients with type 2 diabetes. If successful, this study has the potential to provide a new treatment strategy for diabetic kidney disease in humans.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
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
Omega 3 Polyunsaturated Fatty Acid Analogues In The Treatment Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$418,446.00
Summary
Treatment of diabetes has become an even greater challenge to our community today. The ill health from diabetes arises from the high blood sugar levels. Treatment of diabetic complications such as kidney damage has now become a major goal. This research addresses this problem by trying to find out if a group of novel polyunsaturated fatty acids can target the process initiated by high blood sugar responsible for kidney damage.
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.