Urgent effort underway to learn how diabetes increases heart disease risk

May 8 2006

A researcher at the University of Rochester Medical Center has won the 2006 Thomas R. Lee Career Development Award from the American Diabetes Association (ADA), which includes an $842,400 grant to study how diabetes dramatically increases risk for cardiovascular disease.

The award recognizes the excellence in diabetes-related research achieved by Zheng-Gen Jin, Ph.D., assistant professor in the Department of Medicine and the Cardiovascular Research Institute, and supports his lab's work.

Nearly 21 million Americans have diabetes. The most life-threatening consequences of diabetes are heart diseases and stroke, which strike people with diabetes twice as often as people without the disease. More than 65 percent of deaths in diabetes patients are attributed to heart and vascular disease. Thus, researchers are seeking urgency to understand why people with diabetes are at greater risk. Dr. Jin won the award for his study, titled Molecular Basis for Diabetes-associated endothelial dysfunction, which focuses on how high blood sugar (blood glucose) in diabetes patients contributes to narrowed blood vessels, creating risk for heart attack and stroke.

Dr. Jin was chosen because his ADA grant application was found to have the highest scientific merit in a given fiscal year. The Thomas R. Lee Career Development Award is funded in full by the Estate of Mr. Thomas R. Lee of Norfolk, Virginia, through ADA Research Foundation. The ADA funding for Jin's lab begins this year and runs through 2010.

"I am honored and excited to receive the award because I believe it will help us to improve the understanding of how two deadly diseases are related," Jin said. "Both diabetes and heart disease have reached epidemic levels and are projected to get worse, so we appreciate Mr. Lee's generosity and applaud the ADA's support of the search for better, preventive treatments."

Diabetes mellitus is a long-term disease where patients lose, or see reduced, their ability to effectively process sugar consumed as food. They develop high blood sugar because the body does not produce (type 1 diabetes) or produces too little (type 2 diabetes) insulin, the enzyme that takes sugar from blood and carries it into the cells where it can be used to produce energy. Diabetes can change the chemical makeup of substances found in the blood, which can cause blood vessels to narrow or to clog completely. This process is called atherosclerosis, or hardening of the arteries, and diabetes seems to speed it up.

Jin's lab is focused on the role of oxidative stress in the development of atherosclerosis in patients with Type 2 diabetes. High blood glucose can stimulate the production of highly reactive molecules called free radicals from cells in blood and in blood vessel walls. Oxidative stress occurs when those free radicals overwhelm the antioxidant defence system in cells and cause unwanted reactions with sensitive molecules (e.g. DNA). Beyond the direct cellular damage, oxidative stress also reduces the bioavailability of nitric oxide (NO). NO signals muscle within blood vessels to relax, widening the artery and increasing blood flow. Less NO means blood vessels are less relaxed and open and more likely to clog. Derived from cells lining blood vessels (vascular endothelial cells), NO is believed to counter atherosclerosis.

High blood glucose in patients with diabetes impairs the performance of NO synthases (NOS), the enzymes that generate NO in response to blood flow, according to theory. Jin hopes to soon understand the molecular mechanisms behind this process on the way to creating new drugs that release more nitric oxide when needed to prevent cardiovascular disease in patients with diabetes.

"Diabetes is on the rise in the United States, yet the available funding for research hasn't increased at the same pace," said Don Wagner, chair of the American Diabetes Association Research Foundation. "That's why we believe it's so important to recognize and support the work of scientists like Dr. Jin, whose cutting-edge research is doing so much to improve the quality of life for people who suffer from this disease."

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