What’s Behind Heart Attacks in Type 1 Diabetes?
Myra Lipes, MD
Myra Lipes, MD
Investigator, Joslin Diabetes Center
|ADA Research Funding
Clinical Translational Award
Type 1 diabetes puts patients at huge risk for heart disease: Heart attacks and other cardiovascular complications cause the death of nearly 3 out of every 4 people with type 1 diabetes, compared with just 1 in 4 people in the general population. And while treatments for other complications of type 1 diabetes have come a long way in the past 30 years, these grim numbers haven’t budged a bit.
Researchers have long speculated that there’s something specific to type 1 diabetes that puts patients at such high risk, but what that something might be has been elusive. “It’s been a mystery why patients with type 1 diabetes do so poorly,” says Myra Lipes, a researcher at the Joslin Diabetes Center in Boston.
Lipes’s research, conducted with the support of the American Diabetes Association, suggests the problem may be the same one that triggers type 1 in the first place: an out-of-control immune response. Immune system cells designed to go after specific targets are called “T-cells.” Their presence in the body is an indication that the immune system has been exposed to invaders—or that it has developed sensitivity to proteins in the body itself.
That’s called autoimmunity, and it’s no good. Type 1 diabetes, for example, is caused when the body’s immune system—designed to attack invaders such as bacteria—turns instead on the beta cells in the pancreas that produce insulin. People whose immune systems go haywire once are at greater risk for future problems, such as when a person with type 1 also develops celiac disease, another autoimmune condition.
Lipes suspects this sort of autoimmune attack may be behind the increased rates of heart disease faced by people with type 1 diabetes. After a heart attack, dead and dying cells release proteins. In people with a hair-trigger immune system, these may be mistaken for invaders and spur the immune system to attack the heart itself.
Lipes has done experiments in mice that confirm the connection. “We have published data from a mouse model of type 1 diabetes that heart attacks can trigger an immune attack against the heart muscle,” Lipes says. “These mice develop ‘runaway autoimmunity’: exaggerated, lifelong responses to the body’s own heart proteins.” The big question is whether the post–heart attack immune response can be detected, and successfully treated or avoided altogether. Lipes thinks the answer is yes. “Our initial studies have suggested that the presence of multiple cardiac antibodies can predict whether people are at higher risk for poor outcomes after a heart attack,” she says.
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People with diabetes are also at risk because the first heart attack—the one that triggers the immune system’s attack—may go unnoticed. “Because of neuropathy, maybe they can’t feel when they have a heart attack,” Lipes says. “The patient might have minor damage: a ‘silent’ heart attack.” It’s enough, however, to prompt an immune response that could cause much more serious damage later on.
Using an ADA grant, Lipes is trying to prove her theory—and perhaps save lives. To do so, she’s analyzing a wealth of data already collected in the course of an unrelated experiment. Her collaborators took blood samples, scanned patients’ hearts using MRIs, and performed other tests just after a heart attack and then again six months later. The study numbered hundreds of people, including patients with both types of diabetes, key data for Lipes’s investigation.
By comparing the MRIs (essentially high-resolution pictures of the heart muscle) taken just after a heart attack with those taken six months later, cardiologists can tell if the heart hasn’t healed well. Lipes will then look to see if the people with poorly healed hearts have autoantibody profiles and T-cell responses that signal an attack on the heart, with MRI evidence of inflammation. “We’re seeing if the presence of these autoimmune markers predicts worse outcomes after heart attacks,” she says.
The ultimate goal is to identify the specific T-cells that might be attacking the heart and figure out how big a role the immune response in people with type 1 diabetes plays in poor cardiovascular health.
Armed with that knowledge, doctors could come up with lifesaving therapies tailor-made for people with type 1 diabetes, and potentially help autoimmune-prone people in the general population along the way. “If we can induce T-cell tolerance as we’ve done in animal models, we can prevent this from occurring,” Lipes says. “That would make the early identification of at-risk patients very important.”