Study points to need for approaches that are different from CVD in type 2 diabetes

BOSTON – (April 30, 2015) – Diabetes boosts the risks of developing heart conditions, and patient studies within the past few years have shown that people with type 1 diabetes show significantly higher risk of poor outcomes from cardiovascular disease complications than those with type 2 diabetes. Research led by Joslin Diabetes Center's Myra Lipes, MD, has identified one culprit in heart failure—an autoimmune reaction triggered by heart attacks. In a recent Current Diabetes Reports paper, Dr. Lipes and her colleague Alfonso Galderisi review progress in understanding the autoimmune mechanism and taking steps toward diagnosing and treating it.

“We should be approaching heart disease differently in type 1 diabetes than in type 2 diabetes,” says Dr. Lipes, an Investigator in Joslin’s Section on Immunobiology and Assistant Professor at Harvard Medical School. “There are type 1 diabetes-specific risk factors that lead to worse cardiovascular disease outcomes in this population.” 

She notes, for example, that one large study of Swedish patients found that heart failure is as common among men with type 1 diabetes in their early forties as it is in men without diabetes who are 15 or more years older. The most common cause of heart failure is a heart attack, but patients with type 1 diabetes often experience “silent heart attacks” that lack recognizable symptoms. 

Another Swedish investigation, published in 2014, discovered that even among people with type 1 diabetes who maintain good control of their blood glucose levels, the risk of death from cardiovascular disease is almost triple the rate in the general population. 

In type 1 diabetes, the body's insulin-producing cells are destroyed by an autoimmune reaction. Dr. Lipes and her coworkers have shown in both mice and humans with type 1 diabetes that a similar kind of autoimmune reaction, kicked off by a protein called alpha-myosin heavy chain that is found only in heart muscle, leads to chronic heart inflammation (known as “myocarditis”). 

Following a heart attack, this autoimmune reaction also occurs in people without diabetes, but it is short-lived and turned off as the heart repairs itself. In a subset of people with type 1, however, the reaction never stops. Over time the runaway attack thins and weakens the heart muscle and leads to heart failure.

The Lipes lab has developed a panel of blood tests that detects markers of this autoimmune reaction, which proved effective in an early clinical study published in 2012 and offers the potential for more widespread screening for the syndrome. 

“Our next step is to study this reaction in other type 1 diabetes populations,” says Dr. Lipes. She is working to add the screening panel to related studies of type 1 heart complications underway at Joslin and other research centers.

In work with type 1 diabetes-prone mice, scientists in her laboratory have been able to block the autoimmune response by genetic modifications that created immune tolerance for the alpha-myosin heavy chain protein. This research suggests that it will be possible to create targeted therapies that specifically protect the heart in people with type 1 diabetes.

In the meantime, Dr. Lipes suggests, people with type 1 diabetes should carefully follow standard recommendations for heart-healthy habits in their diet and exercise.

To best address the large burden of heart disease in this population, “we need to further explore mechanisms that are unique or enriched in people with type 1 diabetes,” she adds. “This is a bit of a new area in research on diabetes complications, and cardiovascular disease stands in stark contrast to the improved outcomes we’ve seen in eye disease, kidney disease and other complications.”

Funding for the study came from the American Diabetes Association, the National Institutes of Health, the Seaver Institute and the European Foundation for the Study of Diabetes.

* * *