WUSM receives NHLBI grant to study heart disease in patients with diabetes

Researchers at Washington University School of Medicine in St. Louis have received a $4.7 million grant from the National Heart, Lung, and Blood Institute to investigate heart disease in patients with diabetes.

"Diabetes is an incredibly common problem," says Jean E. Schaffer, MD, the Virginia Minnich Distinguished Professor of Medicine. "It affects a huge swath of the population. Importantly, people with diabetes don't just have a metabolic disorder. They develop complications in many organs. And one of the most deadly complications is heart disease. We're particularly interested in why people with diabetes suffer from unusually severe forms of heart disease."

For reasons not fully understood, people with diabetes are more likely to develop blockages in arteries. After a heart attack, the course of the subsequent heart disease is more aggressive than in people without diabetes. And even independent of blocked arteries, there is evidence that their hearts do not function like those of individuals without diabetes.

According to the Centers for Disease Control and Prevention, almost 26 million Americans are living with type 2 diabetes and another 79 million with undiagnosed diabetes or pre-diabetes, a condition that increases their risk of developing the full-blown variety. With such statistics, it is becoming increasingly important to explore the reasons behind the aggressive progress of cardiovascular disease in patients whose bodies do not properly regulate blood sugar.

Schaffer and her colleagues suspect a likely culprit is abnormal lipid metabolism. Lipids are a class of molecules that include fats, such as fatty acids and triglycerides. Past studies have shown that patients with diabetes store higher levels of these lipids in their heart muscle, likely impairing cardiac function. These lipids appear to lead to inflammation and can also damage important parts of heart cells, such as proteins and DNA, leading to heart muscle dysfunction.

"The problem is that we haven't been able to make strong links between what we measure in a fasting blood sample, like triglycerides and free fatty acids, and the degree of heart muscle dysfunction," Schaffer says. "In this type of heart muscle disorder, these common blood tests are not a good predictor of who is at highest risk for heart disease."

The goal of the new research program is to identify better measures of heart disease in patients with diabetes. The program has four major parts:

Establish a clinically useful method to measure key lipids related to diabetes complications in blood samples.

Identify markers of abnormal lipid metabolism in existing blood samples from clinical trial participants, including those in the Framingham Heart Study. Such large, well-designed clinical trials often have collected both blood samples and non-invasive imaging studies of cardiovascular function such as echocardiograms. Comparing the two may show correlations between markers of abnormal lipid metabolism and heart function.

Design laboratory experiments, including studies in mouse models of diabetes and heart disease, to help understand how the abnormal lipids may contribute to heart muscle dysfunction.

Perform a clinical trial for patients with type 2 diabetes to examine whether a drug that lowers blood lipids improves heart function.

In addition to its own research program, Washington University will serve as the coordinating center among the five institutions chosen to receive funding from the National Institutes of Health (NIH) to study the abnormal metabolism of cardiovascular and lung diseases. The four partnering institutions are Cleveland Clinic, Emory University, National Jewish Health and Weill Cornell Medical College.

"We will be working with the NIH and our partner institutions to help researchers interact and inform new approaches and new ideas in other studies," Schaffer says.

Schaffer emphasizes the multidisciplinary and collaborative nature of the research program and credits the School of Medicine's BioMed 21 initiative for providing the resources to facilitate this type of translational project.