Association of cardiac autonomic neuropathy with subclinical myocardial dysfunction in type 2 diabetes
Open accessAbstract
Objectives The purpose of this study was to investigate the independent association between global cardiac autonomic neuropathy (CAN) and left ventricular (LV) dysfunction in addition to regional associations of LV dysinnervation and function, in patients with type 2 diabetes mellitus (T2DM).Background CAN represents a potential mechanism in the etiology of nonischemic diabetic cardiomyopathy.Methods Clinical measures of CAN based on total spectral power of heart rate variability and cardiac reflex testing and echocardiographic assessment of LV function were performed in 118 patients with type 2 diabetes mellitus. Systolic and diastolic function were defined at rest and peak exercise using peak systolic and peak early diastolic (Em) tissue velocities, calculated in 6 basal- and mid-segments using color tissue Doppler. Iodine 123-metaiodobenzylguanidine imaging was performed in 33 patients to directly quantify global (heart/mediastinum ratio) and regional LV sympathetic integrity.Results Patients with CAN demonstrated higher resting heart rate, systolic and mean blood pressures, aortic stiffness, hemoglobin A(1c), and urine albumin/creatinine ratio, in addition to lower peak heart rate, chronotropic index, and exercise capacity. Diastolic function (Em) was associated with CAN, evidenced by total spectral power (r = 0.42, p < 0.001) and heart/mediastinum ratio (r = 0.41, p = 0.017). Diastolic function (Em) at rest and systolic function (peak systolic tissue velocity) at rest and exercise were significantly reduced in patients with CAN. Furthermore, total spectral power was associated with Em independent of age, hypertension, metabolic factors, and other relevant contributors to LV dysfunction (β = 0.20, p = 0.035). Relative regional tracer deficits indicative of local denervation were predominant in the anterior and lateral walls (p < 0.001). Associations with regional Em, independent of global iodine 123-metaiodobenzylguanidine uptake, were identified exclusively in mid-anterior (β = 0.45, p = 0.01) and mid-lateral walls (β = 0.34, p = 0.03). However, no association was found between regional denervation and systolic or diastolic dyssynchrony.Conclusions The diastolic dysfunction of type 2 diabetes mellitus shows associations with both regional markers of sympathetic integrity and clinical markers of autonomic neuropathy.
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Early detection of CAN may enable tailored interventions that prevent progression and reduce risks of CVD, arrhythmias, myocardial dysfunction leading to CHF, CKD, and all-cause mortality.
“Timely detection of CAN may help implementation of tailored interventions to prevent its progression and mitigate the risk of associated complications, including CVD, cardiac arrhythmias, myocardial dysfunction leading to congestive heart failure (CHF), CKD, and all-cause mortality.547,614,617–625”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [617]
The DCM and CAN discussion reports an association between CAN and subclinical left-ventricular dysfunction in people with type 2 diabetes, supporting the myocardial-dysfunction portion of the claim. It discusses glycemic control as current management but says evidence for direct treatment is not definitive and trials are needed to establish benefits to LV function. It does not show that early detection and tailored interventions prevent progression or reduce CHF, CKD, arrhythmias, CVD, or mortality risks; page numbers were not available in our copy. (LLM, conf=0.86)
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- Authors
- Sacre, J. W., Franjic, B., Jellis, C. L., Jenkins, C., Coombes, J. S., & Marwick, T. H.
- Affiliations
- The University of Queensland (AU)
- Cleveland Clinic (US)
- Corresponding author
- Marwick, Thomas H.
- Venue
- JACC: Cardiovascular Imaging
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 3
- Issue
- 12
- Pages
- 1207-1215
- ISSN
- 1876-7591 (ISSN-L)
- 1936-878X
- OpenAlex
- W1966174453
- Cited by
- 123
- References
- 29
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 11 · 2021: 7 · 2020: 12 · 2019: 6 · 2018: 5 · 2017: 10 · 2016: 10 · 2015: 11 · 2014: 10 · 2013: 7 · 2012: 13
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- JACC. Cardiovascular imaging (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- Figshare (submittedVersion)
- Funders
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- cardiac autonomic neuropathy, type 2 diabetes, left ventricular dysfunction, diastolic dysfunction, heart rate variability, tissue Doppler imaging, left ventricular dyssynchrony, exercise capacity, aortic stiffness, autonomic dysfunction
- MeSH terms
- Aged, Aorta, Autonomic Nervous System, Blood Pressure, Diabetes Mellitus, Type 2, Diabetic Neuropathies, Elasticity, Exercise Test, Female, Heart Rate, Heart Ventricles, Humans, Male, Middle Aged, Cardiomyopathies, Predictive Value of Tests, Reflex, Risk Factors, Tomography, Emission-Computed, Single-Photon, Chi-Square Distribution, Linear Models, Ventricular Function, Left, Exercise Tolerance, Ventricular Dysfunction, Left, Risk Assessment, Echocardiography, Doppler, Color, Myocardial Perfusion Imaging
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