Understanding the link between high-fat diets, insulin resistance, and diabetic heart disease

The relationship between a high-fat diet and increased risk of Type 2 diabetes and heart disease is well-known. But what is the connection and how does it work?

In Type 2 diabetes, the most common form of the disease globally, cells become insensitive to the hormone insulin -; including those in the heart. That insensitivity impairs heart cells' ability to function, leading to diabetic heart disease and a doubling of the risk for heart failure and death. Heart disease is the most common cause of death from diabetes.

But we don't understand how it happens. How do heart cells become insulin insensitive and how does that lead to the heart disease? In my lab, we're trying to see how high-fat diet impacts the cardiomyocytes -; the muscles that make the heart contract -; to be insulin resistant and ultimately damaged."

Jessica Pfleger, assistant professor at the Fralin Biomedical Research Institute at VTC and its Center for Vascular and Heart Research

Pfleger and her lab will study that connection with funding from a new, five-year, $2.5 million grant from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

Pfleger, also assistant professor in the Department of Biological Sciences in Virginia Tech's College of Science, believes the key is a protein called REDD1, the role of which has not been investigated in the heart. She suspects high-fat diets keep the protein from doing its part to help heart cells remain insulin-sensitive.

Typically, the pancreas produces insulin, which is crucial to cells being able to take up blood sugar, or glucose, and convert it to energy.

In Type 2 diabetes, the body develops insulin resistance, which hinders cells' ability to make needed energy. Unused glucose builds in the blood and weakens cells. In heart cells, that lack of energy can affect the heart, sometimes fatally.

Doctors treat this kind of diabetes by managing blood sugar and giving insulin, which targets the downstream symptoms of the disease – with limited effectiveness and without addressing the disease's root causes.

"We try to control the blood sugar and other downstream effects, but it's hard to do that because we don't really understand the full extent of what's happening in insulin resistance," Pfleger said. She aims to identify causes of insulin resistance, and she believes the connection between high-fat diet and the REDD1 protein's performance is key.

"We predict that restoring the function of this protein will restore insulin sensitivity and prevent cardiac dysfunction," Pfleger said. "Investigating these connections could be key to developing new treatments for Type 2 diabetes and diabetic heart disease."

Parallel to this study, Pfleger and her lab are investigating additional ways to restore insulin sensitivity in Type 2 diabetes. 

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