Potential new therapy may reduce heart failure in people with type 2 diabetes

Researchers have identified a potential new therapy that may reduce the incidence of heart failure in patients with type 2 diabetes, according to a study published in The Journal of Clinical Investigation.

Cardiovascular disease is the leading cause of death in people with type 2 diabetes. The main feature is diabetic cardiomyopathy, where changes occur in heart structure and function. This ventricular dysfunction develops independent of hypertension or coronary artery disease.

The molecular link between diabetes and cardiomyopathy is not well understood, so scientists from University of Texas Southwestern Medical Center set out to evaluate a possible role of FoxO proteins in diabetic cardiomyopathy.

The FoxO (forkhead box proteins, O) family of transcription factors plays a key role in cellular processes including cell growth, metabolism, and survival.

FoxO proteins are downstream targets of insulin signaling. They also mediate feedback control to govern insulin sensitivity and glucose metabolism.

Researchers found that FoxO activity was critically linked with development of cardiomyopathy. First, they determined that FoxO proteins were persistently activated in the hearts of mice with diabetes either from genetic mutation or induced by a high-fat diet.

Researchers then discovered that heart failure induced by a high-fat diet requires FoxO activation. In particular, the findings suggest that the activation of FoxO1 specifically, induced by metabolic stress, is central to the development of cardiomyopathy.

However, when scientists deleted FoxO1 in the cardiac cells of mice, it helped preserve cardiac function and insulin responsiveness.

“Together, these data suggest that activation of FoxO1 is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease,” wrote the authors in the study.

Here in the United States, about 25.8 million people or 8.3 percent of the US population, have type 2 diabetes. The disease affects more than 180 million people around the world. The number of people living with the disease is projected to increase to 300 million by 2025.

Source: The Journal of Clinical Investigation, National Institutes of Health

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