High blood sugar in type 1 diabetes tied to cardiac autoimmunity: Circulation
USA: High blood sugar (hyperglycemia) is associated with cardiac autoimmunity in patients with type 1 diabetes (T1D), according to recent findings. The findings, presented at the Heart in Diabetes CME Conference (virtual meeting), suggest a role for autoimmune mechanisms for CVD development in T1D patients. The study was published in the journal Circulation.
According to Myra A. Lipes, an assistant professor of medicine at Harvard Medical School, T1D patients are at a five- to tenfold increased risk for CV events versus the general population, particularly those with high blood sugar levels and type 1 diabetes. Poor blood sugar control is the strongest modifiable risk factor for CVD in type 1 diabetes unlike in type 2 diabetes. However, little is known about mechanisms specific to T1D. Myocardial injury can induce persistent cardiac autoimmunity in T1D. Persistently high blood sugar or Chronic hyperglycemia causes myocardial injury, raising the possibility that hyperglycemia-induced cardiac autoimmunity could contribute to long-term CVD complications in T1DM.
Lipes and colleagues earlier developed assays for a panel of cardiac autoantibodies and found evidence of cardiac autoimmunity among people with type 1 diabetes after MI, after models demonstrated myocardial infarction induced the production of cardiac antibodies in mice with type 1 diabetes.
They found alpha-myosin to be the main cardiac target of anti-cardiac immune response. Furthermore, there was positivity for more than one antibody in 83% of patients with type 1 diabetes post-MI vs. 15% for those with type 2 diabetes post-MI.
The landmark Diabetes Control and Complications Trial (DCCT) tested whether an intensive treatment regimen designed to maintain blood glucose concentrations as close to normal as possible would affect the appearance or progression of early vascular complications in type 1 diabetes.
Long-term data on the participants who were young and free of CVD at baseline, were available from the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study (mean diabetes duration, 28 years; mean age, 49 years).
Key findings of the study include:
- Although the recent HbA1c levels were similar among participants with and without cardiac autoantibodies, the presence of cardiac autoantibodies identified those with worse glycemic control in the past, suggesting that cardiac autoantibodies are markers of long-term glycemic exposure.
- Participants with more autoantibody types had more pronounced changes to the heart.
- There was a markedly greater numbers of autoantibodies in the HbA1c greater than 9% group compared with the less than 7% group.
- 46% of subjects had more than one antibody, 22% had greater than two antibodies, vs. only 2% and 1%, respectively, in the HbA1c less than 7% group.
- No subject in the HbA1c less than 7% group had three or more antibodies.
- There was a similarity in profiles when comparing the DCCT participants with an HbA1c of at least 9% with a separate cohort with heart failure from Chagas cardiomyopathy that is believed to be driven by a form of chronic myocarditis with autoimmunity against alpha-myosin.
- The DDCT low HbA1c group resembled control subjects.
- There was no relationship between blood sugar control and cardiac antibodies in a cohort of people with type 2 diabetes and comparable glycemic control.
- DCCT participants with the highest titers and numbers of cardiac autoantibodies developed CVD events up to 26 years later.
- A single, fatal CV event occurred in the only DCCT participant to test positive for all five antibodies.
- Analyses stratified by number of cardiac autoantibodies also showed that the presence of two autoantibodies was also associated with a threefold increased high sensitivity C-reactive protein (CRP) level, with a median level of 6 mg/L among those with two or more autoantibodies vs. a median high sensitivity CRP of 1.4 mg/L among participants with one or fewer antibodies.
The findings suggested that subclinical inflammation may link cardiac autoantibodies to CVD outcomes.
The study, "Cardiac Autoimmunity Is Associated With Subclinical Myocardial Dysfunction in Patients With Type 1 Diabetes Mellitus," is published in the journal Circulation.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.119.044539
