Autoimmune-related diastolic is associated with heart failure risk in type 1 diabetes

Reviewed by Emily Henderson, B.Sc.April 6, 2020

People with type 1 diabetes, especially those with poor glycemic control, have a significantly higher risk of cardiovascular disease than the general population. Even more mysteriously, in individuals with type 1 diabetes, many of the risk factors for cardiovascular disease do not match the known risk factors associated with type 2 diabetes.

Dr Mylarips, a researcher in the immunobiology section of the Joslyn Diabetes Center at Harvard Medical School, has been working for more than a decade to understand exactly what could lead to such an increased risk of cardiovascular disease. Type 1 diabetics And what can you do about it?

Heart failure, in particular, has recently been recognized as a significant complication of type 1 and there are nationwide register-based studies showing that individuals with poor glycemic control have a 10-fold increased risk of heart failure. In addition, type 1 mortality is higher than type 2 diabetes, suggesting that type 1 diabetes may involve various mechanisms of heart failure. “

Dr. Myra Lipes, Investigator for the Immunobiology Section of the Joslyn Diabetes Center at Harvard Medical School

Given the burden of heart failure in type 1 diabetes, it is important to identify patients at particular risk early.

A new study from Dr. Lips’ lab in Joslin found that in people with type 1 diabetes without known cardiovascular disease, the presence of autoantibodies to myocardial proteins could increase cardiac magnetic resonance (CMR) in left ventricular volume. Indicates that it was associated with imaging evidence (primary pump chamber of the heart), increased muscle mass, decreased pump function (ejection rate), and increased risk of general population failure function. This new study is circulation.

Antibodies are usually produced by the immune system, circulate in the blood, and play an important role in the body’s defenses against infection. In people susceptible to autoimmunity, the body mistakes its protein for threats and attacks. This is what happens with type 1 diabetes. The immune system considers pancreatic beta cells to be invaders and destroys them. In these situations, the antibody is called an autoantibody. Therefore, it is not surprising that this complication of type 1 diabetes is accompanied by an incomplete immune response to cardiomyocytes.

Earlier studies conducted by Dr. Leaps’ group showed that a mouse model of type 1 diabetes developed dilated cardiomyopathy (myocardial weakness) and early heart failure associated with the presence of autoantibodies to myocardial proteins . Her group also shows that poor glycemic control in people with type 1 diabetes is associated with cardiac autoimmunity, not with people with type 2 diabetes. An unexpected finding was a heart failure cohort with cardiomyopathy in Chagas believed to be caused by chronic inflammation of the heart muscle, as well as in young adults and type 1 diabetics without diabetic complications (“Myocarditis”) increases the likelihood of subclinical autoimmune-related myocardial dysfunction in type 1 diabetes, “said Lips.

In this study, Lipes needed to determine whether the dilated cardiac phenotype found in mouse models and Chagas patients was also present in people with type 1 diabetes who had these circulating autoantibodies. She and her team used data collected from participants in post-diabetic control and complication testing (DCCT) diabetes interventions and epidemiology of complications (EDIC) follow-up 28 years composed of people who were suffering. As part of the study, participants imaged the heart using CMR, a gold-standard, non-invasive imaging technique for assessing heart structure and function.

“The study measured autoantibodies to myocardial proteins in blood samples collected during CMR imaging of 892 EDIC participants without known cardiovascular disease,” Lipes said. “And we looked at where the presence of cardiac antibodies was associated with CMR evidence of myocardial dysfunction.”

Although recent A1c levels were similar in participants with and without cardiac autoantibodies, the presence of cardiac autoantibodies in the past identified patients with poor glycemic control, It suggests that it is a marker for long-term glycemic exposure. In addition, CMR scans from people with more than one of these autoantibodies showed that the heart was dilated. They categorized patients based on the number of circulating autoantibodies. This indicates that people with more of these particular autoantibodies showed more pronounced changes to the heart. These findings do not diminish after adjusting for conventional cardiovascular risk factors, suggesting that these changes are primarily due to cardiac autoimmunity.

They knew from previous studies that the heart could have structural and functional changes related to the metabolic problems of diabetes itself. However, these relationships were relatively mild. For example, higher A1C levels were associated with a slightly smaller left ventricular volume that was not clinically significant. However, this study shows that elevated A1C levels can trigger a new autoimmune response and another widespread method of damaging the heart, leading to the expansion and deterioration of functions that are at high risk for heart failure. Is suggested.

“This refers to a new process involving the heart and is associated with poor glycemic control in type 1 diabetes,” Lipes said.

Because heart autoantibodies can be detected by simple blood tests, this study opens new avenues for detecting possible heart failure in patients with type 1 diabetes.

“Given the heavy burden of heart failure in type 1 diabetes, cardiac antibodies may be able to identify people at high risk of developing heart failure early,” said Lipes. “And of course, understanding the underlying causes of heart failure is important because it could lead to targeted treatment approaches to improve outcomes in these patients.”