About 65 percent of people with diabetes die of heart- and circulation-related complications. Yet physicians’ standard arsenal of cardiovascular therapies is not always effective in this specific population.
It will take an army of experts to understand and help resolve such a complex medical challenge, according to researchers at Washington University School of Medicine in St. Louis. To that end, the school just received a new type of planning grant through the National Institutes of Health’s (NIH) Roadmap for Medical Research.
The three-year, $1.8 million grant will help bring together a multidisciplinary team from 13 departments at the university as well as experts from Kansas City and elsewhere in Missouri to develop a plan for an Exploratory Center for Interdisciplinary Research focused on the cardiovascular effects of metabolic disorders such as diabetes. After the planning phase is complete, the group will submit a follow-up proposal for the center.
“With these new Exploratory Centers, we hope to remove roadblocks to collaboration so that a true meeting of minds can take place that will broaden the scope of investigation, yield fresh and possibly unexpected insights, and create solutions to biomedical problems that have not been solved using traditional, disciplinary approaches,” says NIH Director Elias A. Zerhouni, M.D.
Larry J. Shapiro, M.D., executive vice chancellor for medical affairs and dean of the School of Medicine, says, “We are honored and excited to be part of the NIH’s major new Roadmap initiative in research funding. We share the NIH’s vision of advancing medical science by fostering interdisciplinary programs. This grant is a testament to our faculty’s successful application of that philosophy in cardiovascular, diabetes and obesity research and is a critical step in launching a broad-based crossdisciplinary center.”
The School of Medicine will supplement the grant by investing additional funding in pilot projects and by providing infrastructure and resources through BioMed 21, the school’s strategic initiative to rapidly bring advances in basic science to the patient’s bedside.
“This project is one example of how BioMed 21 will attack complex biomedical problems through interdisciplinary teams of scientists who think outside the box and rapidly move things forward,” says the project’s principal investigator, Daniel P. Kelly, M.D., professor of medicine, of molecular biology and pharmacology and of pediatrics. “Type 2 diabetes is an alarming problem in the United States right now, and we are very excited to have been given the opportunity to work with the NIH on a plan for a center dedicated to this critical health care issue.”
The initiative will focus on the cardiovascular complications of type 2 diabetes and a precursor to diabetes called metabolic syndrome. The body’s metabolism, or the way it obtains energy to function, changes in metabolic syndrome. Both conditions are associated with obesity and a variety of risk factors for cardiovascular disease, including high blood pressure and triglycerides.
For example, the body normally gets its energy from both fat and glucose. But people with diabetes have significant trouble using glucose for energy. Since these individuals also tend to have excess amounts of fat, Kelly and his team believe organs – including the heart – begin to rely more and more on fat for energy.
“We think changes in the heart’s fat metabolism make diabetics more susceptible to cardiovascular complications like heart attack and stroke,” Kelly explains. “It also may explain why our standard therapies are much more effective in treating cardiovascular patients without diabetes than those with the disease. We need to understand more about the diabetic heart in order to devise new treatment strategies specifically tailored for this population.”
His group already has developed the first mouse models that mimic the diabetic heart by manipulating genes involved in fat metabolism, rather than by triggering the development of diabetes itself. They have begun to use the models to characterize the changes in heart metabolism associated with diabetes, thanks in large part to the School of Medicine’s Mouse Cardiovascular Phenotyping Core – a mouse “heart hospital” used by multiple institutions and companies throughout the country that allows researchers to study mice using the full spectrum of diagnostic tools available for humans.
Kelly says the ultimate goal is to develop a panel of tests that can be used to diagnose cardiovascular conditions in people with diabetes and help determine the best course of treatment. But to do so, research must move beyond mouse models and small clinical trials.
That’s why his team has partnered with experts in Kansas City, led by John A. Spertus, M.D., director of outcomes research for Saint Luke’s Mid America Heart Institute and a professor at the University of Missouri – Kansas City. Spertus and scientists at Yale University recently established a Cardiovascular Outcomes Research Consortium, pooling the resources and patient populations of 16 clinical research institutions, including Washington University, to expedite and enhance the transition from laboratory findings to clinical advances.
“Washington University is very strong in fundamental research and in small patient trials,” Kelly says. “By partnering with Spertus’ team and with the clinical research consortium, we now have the prime testing ground for our basic science discoveries.”
Developing a plan to accelerate basic discovery research and the clinical implementation of findings from these studies are the two cornerstones of the center that will be planned in the next three years.
The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons 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.