Autoimmunity-Associated Heart Dilation Linked to Heart Failure Risk in Type 1 Diabetes

Individuals with type 1 diabetes, specifically those with poor glycemic control, are at an greater risk for cardiovascular disease than the general population, according to a study by Joslin Research. Additionally, in those with type 1 diabetes, many of the risk factors for cardiovascular disease do not line up with the known risk factors associated with type 2 diabetes, according to the study.

The research shows that among people with type 1 diabetes without known cardiovascular disease, the presence of autoantibodies against heart muscle proteins was associated with cardiac magnetic resonance (CMR) imaging evidence of increased volume of the left ventricle, increased muscle mass, and reduced pumping function. These features are associated with a higher risk of failure in the general population, the researchers noted.

Previous studies have shown that mouse models of type 1 diabetes developed dilated cardiomyopathy and early heart failure associated with the presence of autoantibodies directed against heart muscle proteins. In addition, prior studies by the Joslin Research group found that poor glycemic control in patients with type 1 diabetes was associated with cardiac autoimmunity.

The previous studies unexpectedly showed similar cardiac autoantibody levels in the patients with type 1 diabetes, who were young adult and without diabetes complications, and a heart failure cohort with Chagas’ cardiomyopathy, which is thought to be caused by chronic inflammation of the heart muscle. This raised the possibility of a subclinical autoimmune-associated myocardial dysfunction in type 1 diabetes, according to the study authors.

In the current study, Myra Lipes, MD, and her team wanted to determine whether the dilated heart phenotype seen in mouse models and Chagas’ patients was also present in people with type 1 diabetes who had these circulating autoantibodies. The team used data from participants involved in the post-Diabetes Control and Complications Trial Epidemiology of Diabetes Interventions and Complications follow-up study.

This study consisted of people who had type 1 diabetes for an average of 28 years. The participants had their heart imaged using CMR to measure autoantibodies to heart muscle proteins in blood samples taken from the time of CMR imaging. After, the team examined where the presence of cardiac antibodies was associated with CMR evidence of myocardial dysfunction, according to the study authors.

The findings showed that although the recent A1C levels were similar in participants with and without cardiac autoantibodies, the presence of cardiac autoantibodies identified patients with worse glycemic control in the past. This suggests that cardiac autoantibodies are makers of long-term glycemic exposure.

In addition, the team found that the CMR scans from people with 2 or more of these autoantibodies showed dilated hearts. They sorted patients into categories based on numbers of circulating autoantibodies, which indicated that people with more of these specific autoantibodies had more pronounced changes to the heart.

These findings did not decline after adjusting for traditional cardiovascular risk factors, which suggests that these changes were primarily due to cardiac autoimmunity, according to the study. Although previous research showed that the heart can have structural and functional changes related to the metabolic problems of diabetes itself, these relationships were relatively modest.

This study suggests that higher A1C levels can trigger an additional autoimmune response that damages the heart in a different, more pronounced way that leads to functions connected to a high risk of heart failure, according to the researchers.

This new study suggests future research should focus on detecting the potential for heart failure in patients with type 1 diabetes.

“Given the high burden of heart failure in type 1 diabetes, cardiac antibodies may enable the early identification of people at higher risk of developing heart failure,” Lipes said in a press release. “And, of course, understanding the underlying cause of heart failure is important since it could lead to targeted therapeutic approaches to improve outcomes in these patients.”

REFERENCE

Joslin Research ties autoimmunity-associated heart dilation to potential heart-failure risk in type 1 diabetes [news release]. Boston, MA; Joslin Research: March 31, 2020. https://www.joslin.org/about/news-media/joslin-research-ties-autoimmunity-associated-heart-dilation-potential-heart#. Accessed April 9, 2020.