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Cited by 1,255Heart Rate Variability and Autonomic ControlCardiovascular Syncope and Autonomic DisordersDiabetes Management and Research

Diabetic cardiovascular autonomic neuropathy

Vinik, Aaron I., Ziegler, Dan·2007·Circulation
DOI 10.1161/circulationaha.106.634949
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Abstract

O ne of the most overlooked of all serious complications of diabetes is cardiovascular autonomic neuropathy (CAN), [1][2][3] which encompasses damage to the autonomic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics.4 The present report discusses the clinical manifestations (eg, resting tachycardia, orthostasis, exercise intolerance, intraoperative cardiovascular liability, silent myocardial infarction [MI], and increased risk of mortality) in the presence of CAN.It also demonstrates that autonomic dysfunction can affect daily activities of individuals with diabetes and may invoke potentially life-threatening outcomes.Advances in technology, built on decades of research and clinical testing, now make it possible to objectively identify early stages of CAN with the use of careful measurement of autonomic function and to provide therapeutic choices that are based on symptom control and that might abrogate the underlying disorder. Epidemiology of CANLittle information exists as to frequency of CAN in representative diabetic populations.This is further complicated by the differences in the methodology used and the lack of standardization.Fifteen studies using different end points report prevalence rates of 1% to 90%. 1 The heterogenous methodology makes it difficult to compare epidemiology across different studies.CAN may be present at diagnosis, and prevalence increases with age, duration of diabetes, and poor glycemic control.CAN also cosegregates with distal symmetric polyneuropathy, microangiopathy, and macroangiopathy.Age, diabetes, obesity, and smoking are risk factors for reduced heart rate variability (HRV) 5 in type 2 diabetes.Thus, there may be selectivity and sex-related differences among the various cardiovascular risk factors as to their influence on autonomic dysfunction.6 HbA1c, hypertension, distal symmetrical polyneuropathy, retinopathy, and exposure to hyperglycemia were shown to be risk factors for developing CAN in type 1 diabetes.7 Clinical Manifestations of CAN Resting TachycardiaWhereas abnormalities in HRV are early findings of CAN, resting tachycardia and a fixed heart rate are characteristic late findings in diabetic patients with vagal impairment.8 Resting heart rates of 90 to 100 bpm and occasional heart rate increments up to 130 bpm occur.The highest resting heart rates have been found in patients with parasympathetic damage, occurring earlier in the course of CAN than sympathetic nerve function; in those with evidence for combined vagal and sympathetic involvement, the rate returns toward normal but remains elevated.A fixed heart rate that is unresponsive to moderate exercise, stress, or sleep indicates almost complete cardiac denervation.8 Thus, heart rate may not provide a reliable diagnostic criterion of CAN in the absence of other causes unless it is increased by more than 100 bpm. Exercise IntoleranceAutonomic dysfunction impairs exercise tolerance, 9 reduces response in heart rate and blood pressure (BP), 10 and blunts increases in cardiac output in response to exercise.11,12 Diabetic patients who are likely to have CAN should be tested for cardiac stress before undertaking an exercise program.9 Patients with CAN need to rely on their perceived exertion, not heart rate, to avoid hazardous levels of intensity of exercise.13 Presently, there is inadequate evidence to recommend routine screening of asymptomatic diabetic patients with an exercise ECG test.Emerging data support the utility of stress imaging testing in identifying diabetic patients with preclinical coronary artery disease, particularly patients with high-risk features, and comorbidities such as long-standing disease, CAN, multiple chronic renal failures, resting ECG abnormalities, and peripheral artery disease.14 Intraoperative and Perioperative Cardiovascular InstabilityPerioperative cardiovascular morbidity and mortality are increased 2-to 3-fold in patients with diabetes.Compared with nondiabetic subjects, diabetic patients undergoing general anesthesia may experience a greater degree of decline in heart rate and BP during induction of anesthesia and less of an increase after tracheal intubation and extubation.Vasopressor support is needed more often in diabetic individuals with CAN than in those without CAN.15 The normal autonomic response of vasoconstriction and tachycardia does not completely compensate for the vasodilating effects of anesthesia.There is an association between Continuing medical education (CME) credit is available for this article.Go to http://cme.ahajournals.orgto take the quiz.

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Crossref · 10.1161/circulationaha.106.634949

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  • CAN impairs exercise tolerance and lowers maximal HR.

    “CAN also impairs exercise tolerance and lowers maximal HR ( 131 , 265 ).”

    From Exercise and Type 2 Diabetes (2010) · cites this paper as [265]

  • The presence of CAN doubles the risk of mortality and indicates more frequency of silent myocardial ischemia, orthostatic hypotension, or resting tachycardia.

    “The presence of CAN doubles the risk of mortality ( 48 , 265 ) and indicates more frequency of silent myocardial ischemia ( 265 ), orthostatic hypotension, or resting tachycardia ( 76 , 177 ).”

    From Exercise and Type 2 Diabetes (2010) · cites this paper as [265]

  • Slower HR recovery after PA is associated with mortality risk.

    “Slower HR recovery after PA is associated with mortality risk ( 38 , 265 ).”

    From Exercise and Type 2 Diabetes (2010) · cites this paper as [265]

    The Increased Risk of Mortality section links impaired heart-rate variability and cardiovascular autonomic neuropathy to mortality, but does not discuss heart-rate recovery after physical activity. A search for post-exercise heart-rate recovery found exercise-related passages in Management of Exercise Intolerance, but none linking recovery speed to mortality risk. (LLM, conf=0.76)

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Research works printed but not linked: 7

  1. [3]3. Maser R, Lenhard M, DeCherney G. Cardiovascular autonomic neurop- athy: the clinical significance of its determination. Endocrinologist. 2000;10:27-33.
  2. [4]4. Schumer MP, Joyner SA, Pfeifer MA. Cardiovascular autonomic neu- ropathy testing in patients with diabetes. Diabet Spectr. 1998;11: 227-223.
  3. [18]18. Position paper. Orthostatic hypotension, multiple system atrophy (the Shy Drager Syndrome). J Auton Nerv Syst. 1996;58:123-124.
  4. [21]21. Vinik A, Erbas T. Neuropathy. In: Ruderman N, Devlin JT, Schneider SH, Kriska A, eds. Handbook of Exercise in Diabetes. 2nd ed. Alex- andria, Va: American Diabetes Association; 2001:463-496.
  5. [45]45. Stevens M, Dayanikli F, Raffel D, Allman K, Standford T, Feldman E, Wieland D, Corbett J, Schwaiger M. Scintigraphic assessment of region- alized defects in myocardial sympathetic intervation and blood flow regulation in diabetic patients with autonomic neuropathy. J Am Coll Cardiol. 1988;31:1575-1584.
  6. [80]80. Ziegler D, Langen K, Weise F. Contribution de l'imagerie scin- tigraphique a l'etude de l'innervation sumpathique. In: Valensi P, Feuvray, D, Sach R-N, eds. Coeur et Diabete. Paris, France: Editions Frison-Roche; 1999:443-455.
  7. [103]103. KEY WORDS: diabetes mellitus Ⅲ cardiovascular diseases Ⅲ diabetic neuropathies Go to http://cme.ahajournals.org to take the CME quiz for this article.

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Authors
Vinik, A. I., & Ziegler, D.
Affiliations
Deutsches Diabetes-Zentrum e.V. (DE)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2007-01-23
Volume
115
Issue
3
Pages
387-397
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.106.634949
OpenAlex
W2104600471
Cited by
1,255
References
110
Citations by year
2026: 52 · 2025: 46 · 2024: 49 · 2023: 75 · 2022: 74 · 2021: 70 · 2020: 77 · 2019: 74 · 2018: 67 · 2017: 65 · 2016: 78 · 2015: 80 · 2014: 112 · 2013: 75 · 2012: 67
FWCI
6.99
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
cardiac autonomic neuropathy, diabetes complications, heart rate variability, orthostatic intolerance, exercise intolerance, silent myocardial infarction, autonomic function testing, prevalence, risk factors, type 1 diabetes, type 2 diabetes, sympathetic dysfunction, mortality risk, distal symmetric polyneuropathy
MeSH terms
Autonomic Nervous System, Cardiovascular Diseases, Diabetic Neuropathies, Humans, Risk Factors, Tachycardia, Death, Sudden, Cardiac, Myocardial Ischemia, Diabetes Complications

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