The Not-so-Sweet Truth about Diabetes and Cardiovascular Disease

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The Centers for Disease Control and Prevention reports that 1 in 10 people in the U.S. have diabetes. About 90 to 95% of people with diabetes have Type 2, meaning their body can’t process and break down food properly. This leads to higher blood sugar, increased circulating fatty acids and insulin resistance. Type 2 diabetes often leads to other complications, such as vision loss, kidney disease and heart disease.

Diabetic cardiomyopathy is a form of diabetes-related heart disease. It’s defined by cardiac dysfunction and fibrosis (tissue scarring) in someone with diabetes who doesn’t have other heart disease-related risk factors, such as high blood pressure and coronary artery disease. But why does diabetes cause heart problems? It has to do with how the cells react to energy demands and stress.

The heart requires a lot of energy to function. You may remember from high school biology that mitochondria are the powerhouse of the cell, and it generates energy for cellular functions. Our cells produce energy by breaking down nutrients from the food we eat to make adenosine triphosphate (ATP) molecules that are used for several vital cellular functions. One of the ways to make ATP is the breakdown of glucose, and another is fatty acid oxidation (FAO), or the breakdown of fat molecules. People with diabetes have more fatty acids available in the heart, and, due to insulin resistance, the cells are not able to take up as much glucose. Sole reliance on FAO begins as the heart struggles to keep up with energetic demands.  However, FAO produces less ATP than glucose breakdown, leading to increased cellular stress and cellular death.

Cellular stress is just what it sounds like—the cells must work harder to stay alive. When we’re stressed out, we often choose the tasks that seem the most important and may drop the ball on other tasks that still require our attention. Our choosing one over the other may have consequences. The same thing happens in the cells. Each organelle has its own job in the cell to maintain function.

The endoplasmic reticulum (ER) is an organelle responsible for making proteins and lipids (fats). When the ER is stressed, most protein production stops, and the ER focuses on reducing the stressors by only making proteins that combat stress. One stress response protein is called REDD1. At low amounts, REDD1 can help the cell remove stress, but when REDD1 or other stress response proteins can’t resolve ER stress, the cell has no choice but to shut down. As cells die, fibrosis causes the heart to stiffen, making it harder for it to pump blood through the body.

My lab’s work, published in the American Journal of Physiology-Endocrinology and Metabolism, highlights this connection between diabetes and heart disease. We show that ER stress-induced production of REDD1 can cause an inflammatory response in the hearts of mice with type 2 diabetes, which we believe contributes to cardiac dysfunction. More studies need to be done to better understand how ER stress and other kinds of cellular stress lead to heart dysfunction. Once we know more about it, we can develop better treatment options for people with diabetes-related heart disease.

Shaunaci Stevens is a PhD graduate fellow in cellular and molecular physiology at the Penn State College of Medicine in Hershey. Her research focuses on cellular stress responses in diabetes-induced heart disease.

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