Epicardial Fat is a Modifiable Risk Factor for Type 2 Diabetics

Research by Gianluca Iacobellis, M.D., Ph.D., professor of clinical medicine in the Division of Endocrinology, Diabetes and Metabolism at the University of Miami Miller School of Medicine, has shown that a drug commonly prescribed for patients with type 2 diabetes can significantly reduce epicardial adipose tissue, the fat around and within the heart. Iacobellis also pioneered and developed a simple, inexpensive and non-invasive test that can measure epicardial fat thickness and track the amount lost following drug therapy.

A cardiac ultrasound photo showing epicardial fat within the yellow outline and its greatest thickness depicted by the red line according to the method pioneered and validated by Dr. Iacobellis.

“My recent studies have shown that people with diabetes — known to be at higher risk for cardiovascular diseases — tend to have epicardial fat-producing genes that are different from those of people without diabetes,” said Iacobellis. “Epicardial fat is especially dangerous because it embeds itself in the outside of the heart wall, affecting the functioning of the heart, and it has a direct correlation with coronary artery disease and diabetes — even in people who aren’t obese. My goal has been to develop a test to measure epicardial fat, determine which patients with type 2 diabetes are most at risk and then to have a therapeutic way of shrinking the epicardial fat before it can cause significant damage to the heart.”

Iacobellis, who has spent 15 years conducting related research, and has published 120 journal articles and several books on the subject, has made significant progress. First, he demonstrated that epicardial fat could be detected and measured using conventional cardiac ultrasound.

“Compared to an MRI or CT, ultrasound testing is extremely inexpensive, readily available, non-invasive and takes less time,” said Iacobellis.

Then he conducted a clinical trial in which half of the subjects — all of whom had type 2 diabetes and were obese — continued using metformin only and half were also given the supplemental drug liraglutide. Liraglutide is well established as a medication that lowers glucose levels and causes a modest weight loss. A recent clinical trial had also shown that it can be associated with a lower risk of cardiovascular events, although whether that was due to its effect on visceral fat was unknown. Iacobellis’ trial provided the answer.

“We found that the subjects also using liraglutide had a significant — almost 40 percent — and rapid reduction in the amount of epicardial fat during the six-month trial,” he said, “versus no change in the control group. The liraglutide subjects also experienced a reduction in overall body fat, but that loss, on average, was only 10 percent. The disproportionate loss of epicardial fat indicates that liraglutide may have a direct effect on the fat.”

Iacobellis, as first author, published the fat-reduction portion of his team’s findings in an article, “Liraglutide Causes Large and Rapid Epicardial Fat Reduction,” in the February issue of the journal Obesity. His co-authors were Miller School endocrinologists Mahshid Mohseni, Ph.D., Suzy D. Bianco, Pharm.D., Ph.D., and Pritisheel K. Banga, D.O.

A second article with Iacobellis as first author deals with the gene-expression implications. “Human Epicardial Fat Expresses Glucagon-like Peptide 1 and 2 Receptors Genes,” is scheduled to be published this summer in the journal Hormone and Metabolic Research. Co-authors are Miller School geneticists Vladimir Camarena, M.D., Ph.D., graduate student David Sant, and Gaofeng Wang, Ph.D.

Now Iacobellis is recruiting subjects for a new trial and is seeking funding for related collaborative research with Miller School cardiologists and oncologists.

“We have demonstrated through our research that we have the non-invasive means to detect the presence of epicardial fat in patients before they become ill,” he said. “We are also developing clinical treatments to reduce epicardial fat, and through those treatments, our patients’ associated risk of cardiovascular disease.”

Tags: epicardial fat, Gianluca Iacobellis, Hormone and Metabolic Research, Liraglutide, Miller School of Medicine, University of Miami