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Cited by 117Diabetes and associated disordersDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

Glycemic Control, Cardiac Autoimmunity, and Long-Term Risk of Cardiovascular Disease in Type 1 Diabetes Mellitus: A DCCT/EDIC Cohort–Based Study

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Sousa, Giovane R., Pober, David, Galderisi, Alfonso, Lv, HuiJuan, Yu, Liping, Pereira, Alexandre C., Doria, Alessandro, Kosiborod, Mikhail +1 more·2019·Circulation
DOI 10.1161/circulationaha.118.036068PMC PMC6361693
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Abstract

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.

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  • Patients with type 1 diabetes exhibit elevated levels of anti-heart autoantibodies.

    “Sousa et al reported that patients with type 1 diabetes, an autoimmune condition, exhibit elevated levels of anti-heart autoantibodies”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [156]

    The Results section (page not supplied) reports substantially higher mean cardiac autoantibody levels in patients with type 1 diabetes whose HbA1c was ≥9.0% than in those whose HbA1c was ≤7.0%. The claim omits this glycemic-control qualifier and implies the elevation applies to patients with type 1 diabetes generally. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In patients with type 1 diabetes, anti-heart autoantibody levels correlate with cardiac dysfunction and increased cardiovascular disease risk.

    “which correlate with cardiac dysfunction and increased cardiovascular disease risk.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [156]

    The Results section, “Cardiac autoantibodies and future CVD events” (page unavailable), associates cardiac autoantibody positivity with later cardiovascular events in patients with type 1 diabetes. The cited passages do not establish a correlation with cardiac dysfunction specifically; the study assessed coronary calcification and CVD events rather than a measure of cardiac function. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Sousa, G. R., Pober, D., Galderisi, A., Lv, H., Yu, L., Pereira, A. C., Doria, A., Kosiborod, M., & Lipes, M. A.
Affiliations
  • Brigham and Women's Hospital (US)
  • Joslin Diabetes Center (US)
  • University of Colorado Anschutz (US)
  • Universidade de São Paulo (BR)
  • University of Missouri–Kansas City (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-02-05
Volume
139
Issue
6
Pages
730-743
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.118.036068
PMC
PMC6361693
OpenAlex
W2902018714
Cited by
117
References
10
Citations by year
2026: 9 · 2025: 18 · 2024: 12 · 2023: 18 · 2022: 20 · 2021: 21 · 2020: 11 · 2019: 8
FWCI
8.96
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL073168, R01HL077554)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK103609, R01DK103699, R01DK072090, P30DK036836)
  • NIH Clinical Center
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 1 diabetes, glycemic control, cardiac autoimmunity, cardiac autoantibodies, cardiovascular risk, coronary artery calcification, hyperglycemia, myocardial injury, type 2 diabetes, Chagas cardiomyopathy, C-reactive protein, myocardial infarction, stroke, heart failure, coronary artery bypass grafting, long-term cardiovascular outcomes
MeSH terms
Adult, Autoantibodies, Brazil, Chagas Cardiomyopathy, Diabetes Mellitus, Type 1, Female, HLA Antigens, Humans, Hyperglycemia, Male, Myocardium, Risk, Time Factors, Cohort Studies, Autoimmunity, Prevalence, Case-Control Studies, Young Adult

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