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Complications - Currently Funded

Dr. Andrew Advani (Operating Grant funded 2010-2013; Clinician Scientist Award funded 2009-2014)

St Michael's Hospital (Toronto, ON)

Title: Unravelling the role of SDF-1/CXCR4 signalling in diabetic nephropathy

Kidney disease is a common complication of diabetes. Dr. Andrew Advani is examining the small blood vessels in the kidney that become damaged in diabetes. He is looking at how a certain small protein, called SDF-1, and its receptor interact and if therapies could change this interaction to prevent damage to the small blood vessels.

 

Dr. Nica M. Borradaile (Operating Grant funded 2011-2014)

The University of Western Ontario (London, ON)

Title: Protective effects of NAD+ on endothelial cell survival and angiogenesis during type 2 diabetes

Blood vessel (vascular) diseases are common complications in patients with obesity and type 2 diabetes. Damage to endothelial cells, the cells which line all blood vessels, is caused by high blood glucose and lipids, and once they're injured, their ability to repair further damage is limited. Dr. Borradaile is investigating whether increasing the level of NAD+ – an important molecule involved in endothelial cell survival – will improve the ability of blood vessels to repair the damage that occurs during obesity and type 2 diabetes. This research could help in the development of new drug therapies that would increase NAD+, improve endothelial cell survival, and reduce blood vessel disease in obese people with type 2 diabetes.

 

Dr. Subrata Chakrabarti (Operating Grant funded 2010-2013)

University of Western Ontario (London, ON)

Title: Pathogenesis of diabetic retinopathy

A common complication of diabetes is eye disease (diabetic retinopathy). Dr. Subrata Chakrabarti is examining a special type of genetic material, called miRNA (similar to tiny pieces of DNA), to find out if the way the miRNA acts in people with diabetes can be changed to stop diabetic retinopathy from developing.

 

Dr. David Z. I. Cherney (Clinician Scientist Award funded 2010-2015)

University Health Network (Toronto, ON)

Title: Hemodynamic and molecular mechanisms of hyperfiltration in type 1 diabetes mellitus

Dr. David Z.I. Cherney aims to better understand how diabetes damages the blood vessels, which then causes kidney damage. Kidney and blood vessel damage is caused by a number of factors, including high blood sugar and a system called RAS. When the RAS system is active, it leads to inflammation in the kidneys and blood vessels. Dr. Cherney is investigating the link between high blood sugar, medications that can block RAS, and kidney injury. The aim of this work is to find new ways to stop kidney and blood vessel damage in diabetes.

 

Dr. Ivan George Fantus (Operating Grant funded 2010-2013)

Mount Sinai Hospital (Toronto, ON)

Title: Tyrosine kinase signaling in the pathogenesis of diabetic nephropathy

Dr. Ivan George Fantus is examining specific cells in the kidney which respond to a protein called Src. Src is activated when blood glucose is high, and drugs that inhibit Src seem to be able to slow the development of diabetic kidney disease. Dr. Fantus will examine how activated Src contributes to diabetic kidney disease and whether Src inhibitor drugs can be used as treatment and/or prevention.

 

Dr. Pedro M. Geraldes (Operating Grant funded 2010-2013)

University of Sherbrooke (Sherbrooke, QC)

Title: Role of SHP-1 in PDGF and VEGF inhibition causing poor collateral vessel formation in diabetes.

Dr. Pedro M. Geraldes is looking into blood vessel damage in people with type 1 and type 2 diabetes. This kind of damage can cause injury to the limbs, especially the feet. When blood vessels become damaged, high blood sugar impairs the body's ability to fix the damage. Dr. Geraldes is looking into how high blood sugar causes this impairment, in hopes of finding ways to fix the damage and reduce foot amputations in people with diabetes.

 

Dr. Pedro M. Geraldes (Scholar Award funded 2011-2016)

University of Sherbrooke (Sherbrooke, QC)

Title: Role of PKC delta and SHP-1 on poor collateral vessel formation in diabetes

High glucose levels have been suggested as one of the most important causes of impaired blood vessel formation in people with diabetes. Dr. Geraldes is studying the role of hyperglycemia-induced protein kinase C and SHP-1 activation causing inhibition of new blood vessel formation under ischemic conditions. This research will help us better understand the underlying vascular complications related to high glucose levels in people with diabetes. It may also help in the development of new treatments to promote new blood vessels during ischemia, preventing amputation in people with type 1 and 2 diabetes.

 

Ms. Hui Jun (June) Guo (Doctoral Student Research Award funded 2010-2013)

University of Toronto (Toronto, ON)

Supervisor: Dr. Adria Giacca

Title: Potential treatments of atherosclerosis and restenosis with insulin and insulin sensitizers

Ms. Hui Jun (June) Guo is studying whether resveratrol (a substance found in red wine) and metformin (a blood glucose lowering drug) alone and when combined with insulin, prevent narrowing of blood vessels, as well as decrease fat deposits in blood vessels. This research will find out if resveratrol and metformin treatment has any potential to prevent blood vessel damage in people with type 2 diabetes.

 

Dr. Joan C. Krepinsky (Operating Grant funded 2011-2014)

McMaster University (Hamilton, ON)

Title: SREBP in the pathogenesis of diabetic nephropathy

Diabetes is a common cause of kidney failure, leading to scarring of the filtering units of the kidneys. High glucose levels cause kidney cells to make a protein called transforming growth factor beta (TGFbeta), which induces cells to make scar proteins. Dr. Krepinsky is investigating how TGFbeta activates another protein, called SREBP-1, and how this contributes to the increase in scar proteins. Preventing or slowing the accumulation of scar proteins is important to preserving kidney function in people with diabetes, and blocking SREBP-1 may be a new way to achieve this.

 

Dr. Kathleen M. MacLeod (Operating Grant funded 2012-2015)

University of British Columbia (Vancouver, BC)

Title: Mechanisms and implications of elevated RhoA-ROCK pathway activity in diabetic cardiomyopathy

People with diabetes are at risk for developing a heart disease called diabetic cardiomyopathy, where the heart muscle cells don't work properly and the heart does not beat as well as normal. People with diabetic cardiomyopathy have a higher risk of having, and dying from, a heart attack or heart failure than their healthy peers. There is a specific pathway of chemical signals in heart cells called ROCK. When the ROCK pathway is blocked, the heart beats more normally. Dr. Kathleen MacLeod and her team are examining how blocking ROCK causes this improvement, and what role ROCK plays in the development of heart damage. Finally, Dr. MacLeod will examine if blocking ROCK reduces the damage cause by heart attacks. This research will help better understand the causes of diabetic cardiomyopathy and could lead to new ways to treat this complication.

 

Dr. Bruce A. Perkins (Operating Grant funded 2010-2013)

University Health Network (Toronto, ON)

Title: In-vivo corneal confocal microscopy as a non-invasive biomarker of early neuropathy in type 2 diabetes

Nerve damage is a complication of diabetes that is important to recognize at early stages, but complications, such as foot ulcers, infection, and the need for amputation, do occur. The best method for detecting early nerve damage is to perform a skin biopsy and examine the structure of nerve endings under a microscope. However, the cornea of the eye has similarities to the skin, including the presence of a nerve layer that can be non-invasively visualized using a high-powered microscope called a corneal confocal microscope. Dr. Bruce A. Perkins is testing if the small nerve fibres of the eye, seen under the confocal microscope, can be used as a non-invasive alternative to the skin biopsy test. If this alternative works, it could be paired with routine eye exams for people with diabetes.

 

Dr. Brian B. Rodrigues (Operating Grant funded 2011-2014)

University of British Columbia (Vancouver, BC)

Title: Metabolic basis for diabetic heart disease: role of cardiac lipoprotein lipase

Diabetes increases the risk and severity of heart attack and stroke because the heart of a person with diabetes, which normally uses glucose for energy, switches to using only fats. This has negative end results, including the generation of noxious by-products which kill heart cells, reduce heart function and, ultimately, result in an increased morbidity and mortality. Dr. Rodrigues is examining the role of an enzyme, called lipoprotein lipase (LPL), in this process. This research could help us identify and devise new ways to treat, prevent or delay heart disease in people with diabetes.

 

Dr. Przemyslaw (Mike) Sapieha (Operating Grant funded 2011-2014)

University of Montreal (Montréal, QC)

Title: The involvement of neuronal guidance cues in microvascular degeneration and misguided vessel growth in diabetic retinopathy

Diabetic retinopathy (DR) is the most common complication of diabetes and the leading cause of blindness in working-age individuals. It is characterized by an initial phase of vascular degeneration (blood vessel breakdown) followed by deregulated neovascularization (formation of disorganized microvascular networks). This secondary neovascularization fails to grow into the hypoxic tissue, and instead, these vessels are misdirected toward the vitreous (the clear gel that fills the space between the lens and the retina of the eyeball) and contribute to retinal detachment. Dr. Sapieha is trying to determine if Semaphorin3A (a neuronal guidance cue) – produced by stressed neurons – is involved in mediating the pathological features of DR by participating in retinal vaso-obliteration and by repelling growing neo-vessels from the retina towards the vitreous while hindering desirable retinal revascularization. This research could help in the development of new strategies to prevent and treat retinopathy in patients with diabetes.

 

Dr. Norbert Schmitz (Operating Grant funded 2010-2013)

Douglas Mental Hospital University Institute (Montréal, QC)

Title: Depression and disability in diabetes: a longitudinal community study

Dr. Norbert Schmitz is looking at depression, disability, and diabetes. Type 2 diabetes is associated with a high prevalence of disability, and depression strikes 10 to 30 per cent of people with diabetes. Dr. Schmitz is examining the relationship between neighbourhood environment, physical activity, diet, depression, disability, and quality of life in people with diabetes. The results will provide useful information for the management of diabetes, depressive illness, and associated clinical and behavioural risk factors.

 

Dr. Garry X. Shen (Operating Grant funded 2011-2014)

University of Manitoba (Winnipeg, MB)

Title: Regulatory mechanism for glycated LDL-induced oxidative stress and monocyte-endothelial interactions

Inflammation plays a key role in diabetes and heart disease. Dr. Shen is examining the effect of glycated low density lipoprotein (LDL) or "sugar-modified bad cholesterol" on oxidation and inflammation in vascular cells and animals with diabetes. This research will help to understand the cause of increased heart disease in patients with diabetes, and could help to identify new treatments for improving the management of heart and vascular disease in patients with diabetes.

 

Dr. Sally Y. Shi (Doctoral Student Research Award funded 2012-2015)

University of Toronto (Toronto, ON)

Supervisor: Dr. Minna Woo

Title: Investigating the role of hepatic JAK2 in the development of diabetes and its cardiovascular complications

People with type 2 diabetes have a high risk for heart attacks and strokes, and many of them have fatty liver, which further increases their risk. How fatty liver increases the risk of heart attacks and strokes is not known. A molecule, called JAK2, plays a major role in liver fat metabolism and inflammation. Mice that don't make JAK2 in their liver develop severe fatty liver but surprisingly not diabetes. These genetically engineered mice are therefore a useful experimental tool. Ms. Sally Y. Shi hopes to find out how fatty liver alone without diabetes, or with diabetes will affect the development of heart disease or stroke, which could provide new drug targets to improve the quality of life for people living with diabetes.

 

Dr. André Tremblay (Operating Grant funded 2012-2015)

CHU Sainte -Justine (Montréal, QC)

Title: Role of the CD36-PPAR pathway in lipid and energy metabolism in fat

Obesity can cause fats to be stored not only in fat tissues, but also in the liver, pancreas and muscle cells. Fat storage in these locations can lead to insulin resistance and type 2 diabetes. Dr. André Tremblay and his team hope to find ways to make the body use fats in better ways to avoid the progression to insulin resistance and type 2 diabetes. Dr. Tremblay's studies are focused on molecular pathways in the body that regulate energy balance in fat cells. These studies will provide new information on how obesity and insulin resistance develop. Dr. Tremblay hopes that his information will help future researchers find new ways of treating these conditions and preventing type 2 diabetes from developing.

 

Dr. Alain Veilleux (Postdoctoral Fellowship Award funded 2011-2014)

Center de recherche CHU Sainte-Justine (Québec, QC)

Supervisor: Dr. Emile Levy

Title: Intestinal lipid and lipoprotein metabolism in relation with insulin-resistant and diabetic states in humans

Insulin resistance is the central feature of type 2 diabetes, but is also commonly associated with dyslipidemia. Exaggerated hepatic lipid production and impaired lipid clearance by peripheral tissues are believed to play key roles in the development of dyslipidemia. Recent studies have pointed out the intestine as an important regulator of lipid homeostasis, and previous studies clearly suggest that intestine is an important contributor to the development of dyslipidemia in insulin-resistant state. Dr. Veilleux is investigating whether intestine develops insulin-resistance and inflammatory states, and represents a major contributor to diabetic dyslipidemia. This research could help identify treatment strategies to reduce cardiovascular disease risk in patients with diabetes.

 

Ms. Ying Wang (Doctoral Student Research Award funded 2012-2014)

University of British Columbia (Vancouver, BC)

Supervisor: Dr. Brian B. Rodrigues

Title: Metabolic basis for diabetic heart disease: role of cardiac lipoprotein lipase

In people with diabetes, to compensate for not properly being able to use glucose as a fuel, heart muscle cells start using fats exclusively for energy. This change in fuel source initially helps the heart, but over the long term causes the heart cells to become damaged and leads to heart disease. Ms. Ying Wang aims to investigate how the enzyme called lipoprotein lipase allows the heart cells to make this switching in fuel possible. This may help future researchers find new ways to prevent or delay diabetes-related heart disease.

 

Dr. Geoffrey H. Werstuck (Operating Grant funded 2012-2015)

McMaster University (Hamilton, ON)

Title: Is Accelerated Atherosclerosis a Microvascular Complication of Diabetes Mellitus?

People with diabetes have a higher risk of heart attack and stroke because of a disease of the large blood vessels (macrovascular disease) called atherosclerosis. People with diabetes can also suffer from vision problems, kidney disease and other circulatory problems that are a result of a disease of the very small blood vessels (microvascular disease). Traditionally microvascular and macrovascular disorders are considered as separate problems. We will investigate the possibility that diabetes causes atherosclerosis by injuring the small blood vessels that supply the walls of the large blood vessels. The result of this research could change the way microvascular and macrovascular diseases are treated.

 

Dr. Douglas W. Zochodne (Operating Grant funded 2012-2015)

University of Calgary (Calgary, AB)

Title: Diabetes and Skin Sensation

A common complication of diabetes is damage to the nerves in the hands and feet that can lead to numbness, pain, and poor healing of wounds (called diabetic neuropathy).Dr. Douglas Zochodne and his team have found that – in both type 1 and type 2 diabetes – local, low levels of insulin (too low to change blood glucose) can act on skin nerve fibres and make them grow. Dr. Zochodne and his team are investigating how insulin and other growth factors in the body cause nerve fibers to grow. He hopes to use these factors to help re‐grow nerves, and will investigate if this re‐growth helps improve numbness and wound healing. Through this research, Dr. Zochodne hopes to find new ways to stop or reverse diabetic neuropathy.

Previously Funded