The National Heart, Lung, and Blood Institute has awarded a grant of $4.7 million to researchers at the Washington University School of Medicine in St. Louis to investigate heart disease in diabetic patients.

According to Jean E. Schaffer, MD, the Virginia Minnich Distinguished Professor of Medicine:

“Diabetes is an incredibly common problem. 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.”

Diabetics are more likely to develop blocked arteries than non-diabetics. The reasons for this are not yet fully understood. Diabetics who suffered a heart attack, experience a much more aggressive course of subsequent heart disease than those without diabetes, and there is no evidence that diabetics’ hearts function differently to that of people without the disease independent of blocked arteries.

The Centers for Disease Control and Prevention estimates that nearly 26 million Americans are diagnosed with type 2 diabetes and a further 79 million are undiagnosed diabetes or pre-diabetes, a pre-stage of the full-blown disease. Considering these statistics, it is vital to explore the underlying reasons for the aggressive progress of cardiovascular disease in these patients.

Schaffer and her team believe that abnormal lipid metabolism may be to blame. Lipids belong to a class of molecules that include fats, like fatty acids and triglycerides. Previous research has demonstrated that the heart muscle of diabetic patients contains higher levels of these lipids, which are likely to affect cardiac function and which seem to be leading to inflammation. They can also damage vital parts of heart cells, including proteins and DNA, which leads to a dysfunction of the heart muscle.

Schaffer says:

“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. 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 new research program aims to identify better measures of heart disease in diabetic patients, and is divided into four major parts:

  • The first part is to establish a clinical method, which is beneficial to measure key lipids related to diabetes complications in blood samples.
  • The second part is identifying markers of abnormal lipid metabolism in clinical trial participants’ existing blood samples, including those in the Framingham Heart Study. Well-designed clinical trials like these often have data on collected both blood samples and non-invasive imaging studies of cardiovascular function such as echocardiograms. A comparison of the two may reveal correlations between markers of abnormal lipid metabolism and heart function.
  • Design laboratory experiments, including mouse model studies of diabetes and heart disease, to investigate the method in which abnormal lipids may contribute to heart muscle dysfunction.
  • Conduct a clinical trial for patients with type 2 diabetes to evaluate whether a blood lipid-lowering drug improves heart function.

Washington University will also serve as coordinating center of five institutions that have been selected for funding by the National Institutes of Health (NIH) in order to research the abnormal metabolism of cardiovascular and lung diseases. Aside from Washington University’s own research, the four partnering institutions have been named as Weill Cornell Medical College, Cleveland Clinic, National Jewish Health and Emory University.

Schaffer states: “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,” highlighting the research program’s multidisciplinary and collaborative nature. She also credits the School of Medicine’s BioMed 21 initiative for providing the required resources in order to execute this translational project.

Written by Petra Rattue