Positivity for ≥2 cardiac autoantibodies in type 1 diabetes was associated with a markedly increased risk of cardiovascular events (HR 16.1; 95% CI 3.0-88.2) over a 26-year median follow-up.
Observational (n=427)
Does poor glycemic control and subsequent cardiac autoimmunity increase the long-term risk of cardiovascular disease in patients with type 1 diabetes mellitus?
Poor glycemic control in type 1 diabetes mellitus is associated with the development of cardiac autoimmunity, which strongly predicts long-term cardiovascular disease risk decades later.
Hazard Ratio: 16.1 (95% CI 3–88.2)
Background: Poor glycemic control is associated with increased risk of cardiovascular disease (CVD) in type 1 diabetes mellitus (T1DM); however, little is known about mechanisms specific to T1DM. In T1DM, myocardial injury can induce persistent cardiac autoimmunity. Chronic hyperglycemia causes myocardial injury, raising the possibility that hyperglycemia-induced cardiac autoimmunity could contribute to long-term CVD complications in T1DM. Methods: We measured the prevalence and profiles of cardiac autoantibodies (AAbs) in longitudinal samples from the DCCT (Diabetes Control and Complications Trial) in participants with mean hemoglobin A 1c (HbA 1c ) ≥9.0% (n=83) and ≤7.0% (n=83) during DCCT. We assessed subsequent coronary artery calcification (measured once during years 7–9 in the post-DCCT EDIC Epidemiology of Diabetes Interventions and Complications observational study), high-sensitivity C-reactive protein (measured during EDIC years 4–6), and CVD events (defined as nonfatal myocardial infarction, stroke, death resulting from CVD, heart failure, or coronary artery bypass graft) over a 26-year median follow-up. Cardiac AAbs were also measured in matched patients with type 2 diabetes mellitus with HbA 1c ≥9.0% (n=70) and ≤7.0% (n=140) and, as a control for cardiac autoimmunity, patients with Chagas cardiomyopathy (n=51). Results: Apart from HbA 1c levels, the DCCT groups shared similar CVD risk factors at the beginning and end of DCCT. The DCCT HbA 1c ≥9.0% group showed markedly higher cardiac AAb levels than the HbA 1c ≤7.0% group during DCCT, with a progressive increase and decrease in AAb levels over time in the 2 groups, respectively ( P <0.001). In the HbA 1c ≥9.0% group, 46%, 22%, and 11% tested positive for ≥1, ≥2, and ≥3 different cardiac AAb types, respectively, similar to patients with Chagas cardiomyopathy, compared with 2%, 1%, and 0% in the HbA 1c ≤7.0% group. Glycemic control was not associated with AAb prevalence in type 2 diabetes mellitus. Positivity for ≥2 AAbs during DCCT was associated with increased risk of CVD events (4 of 6; hazard ratio, 16.1; 95% CI, 3.0–88.2) and, in multivariable analyses, with detectable coronary artery calcification (13 of 31; odds ratio, 60.1; 95% CI, 8.4–410.0). Patients with ≥2 AAbs subsequently also showed elevated high-sensitivity C-reactive protein levels (6.0 mg/L versus 1.4 mg/L in patients with ≤1 AAbs; P =0.003). Conclusions: Poor glycemic control is associated with cardiac autoimmunity in T1DM. Furthermore, cardiac AAb positivity is associated with an increased risk of CVD decades later, suggesting a role for autoimmune mechanisms in the development of CVD in T1DM, possibly through inflammatory pathways.
“Her group has also shown that poor glycemic control in patients with type 1 diabetes — but not in those with type 2 diabetes — was associated with cardiac autoimmunity. An unexpected finding was the 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 ('myocarditis'), raising the possibility of a subclinical autoimmune-associated myocardial dysfunction in type 1 diabetes”
Sousa et al. (Thu,) conducted a observational in Type 1 Diabetes Mellitus (n=427). Positivity for ≥2 cardiac autoantibodies vs. Positivity for ≤1 cardiac autoantibodies was evaluated on CVD events (nonfatal myocardial infarction, stroke, death resulting from CVD, heart failure, or coronary artery bypass graft) (HR 16.1, 95% CI 3.0-88.2). Positivity for ≥2 cardiac autoantibodies in type 1 diabetes was associated with a markedly increased risk of cardiovascular events (HR 16.1; 95% CI 3.0-88.2) over a 26-year median follow-up.