Fixing diabetic heart complications is focus of $14 million research grant

A five-year, $14 million grant will establish a center at Washington University School of Medicine in St. Louis that will develop better ways to prevent and treat heart disease in diabetic patients. The grant was awarded by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH).

Diabetics who have heart attacks currently confront a poor prognosis, according to Daniel P. Kelly, M.D., professor of medicine, of pediatrics, and of molecular biology and pharmacology.

“Heart disease is the leading killer of diabetics. When we treat diabetic patients following a heart attack with standard cardiac therapies, they do not respond as well as the non-diabetic patients,” Kelly says. “We want to improve the way we understand and care for diabetics who are at risk of or who have suffered a heart attack.”

The new grant establishes a Specialized Center for Clinically-Oriented Research (SCCOR) in Cardiac Function and Disease at Washington University. Kelly will direct the center, one of the first of a new generation of NIH-sponsored research centers designed to encourage heavy emphasis on clinical research.

“One of the main goals of the new SCCOR grants is to aggressively link research discoveries to improving patient treatments,” Kelly explains. “Over 50 percent of our center’s research will be patient-oriented.”

Kelly is director of the Washington University Center for Cardiovascular Research and co-director of the Cardiovascular Division. In addition to his clinical work with patients at Barnes-Jewish and St. Louis Children’s hospitals, he oversees an extensive research program to develop and study mouse models of diabetes and heart disease. A major research initiative of the new center will be to study heart attacks in animal models and apply the findings toward development of new diagnostics and treatments for human diabetics.

“A primary hypothesis of the research funded by this grant is that too much fat is entering the diabetic heart, where it doesn’t belong,” Kelly explains. “If you don’t treat the fat accumulating in the heart, all the cardiologic therapies in the world may not remedy the heart failure caused by the fat.”

Through research in mouse models, Kelly aims to identify new drugs to eliminate fat in cardiac tissues. Kelly and his colleagues will also use the animal research to identify biochemical markers and genetic factors associated with increased risk of cardiovascular disease and death.

Another major branch of the center’s research will be run by John Spertus, M.D., professor of medicine and health outcomes research at Mid-America Heart Institute and the University of Missouri-Kansas City. To begin the process of applying animal model results to patient populations, Spertus will enroll 4,500 heart attack patients across the nation. Approximately 1,500 of those patients will be diabetic.

“We will compare what we learn from the mice with human diabetic and non-diabetic populations,” Kelly explains. “This will allow us to confirm whether the biomarkers we identify in mice are useful and predictive in humans.”

Spertus also plans to study differences in outcomes based on patient race and ethnicity.

A third facet of the SCCOR grant, led by Howard McLeod, Pharm. D., associate professor of genetics at the School of Medicine, will examine how genetic differences in diabetic patients affect their response to drug therapies.

“The final goal is to develop something called a diabetic cardiovascular panel,” Kelly says. “It will help us stratify diabetic patients based in part on the severity of the metabolic disease, a key step toward choosing treatment strategies.”

The SCCOR grant dovetails with the university’s BioMed 21 project, an initiative that fosters multidisciplinary collaboration to speed the development of new therapies.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.