Cardiovascular autonomic diabetic neuropathy (CADN) is one of the most common diabetes-associated complications. Disturbed heart rate variability (HRV) is very often the earliest symptom, even in clinically asymptomatic patients. The following article offers a topical overview for those working or interested in the fields of diabetology and cardiology.
1. American Diabetes Association, American Academy of Neurology.Consensus statement: Report and recommendations of the San Antonio conference on diabetic neuropathy. Diabetes Care1988;11:592–7.
4. Ziegler DDannehl K, Mühlen Het al.Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses at various stages of diabetic neuropathy. Diabet Med1992;9:806–14.
5.
5. Haslbeck M, Luft D, Neundörfer B et al. Diagnose, Therapie und Verlaufskontrolle der autonomen diabetischen Neuropathie. Evidenzbasierte Diabetes-Leitlinie DDG. Deutsche Diabetes-Gesellschaft. 1. Auflage 2002.
6.
6. Maser REMitchell BD, Vinik AIet al.The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes. A meta-analysis. Diabetes Care2003;26:1895–901.
7.
7. Ewing DJCampbell IW, Clarke FB.The natural history of diabetic autonomic neuropathy. Q J Med1980;49:95–108.
8.
8. Watkins PJMackay DJ.Cardiac denervation in diabetic neuropathy. Ann Intern Med1980;92:304–07.
9.
9. Schrödter D. Diabetes mellitus – eine kardiovaskuläre Erkrankung. 1. Auflage. UNI-MED, Bremen 2002.
11. DCCT Research Group.The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT). Diabetologia1998;41:416–23.
12.
12. Kennedy WRNavarro X, Goetz FCet al.Effects of pancreatic transplantation on diabetic neuropathy. N Engl J Med1990;322:1031–7.
13.
13. Kennedy WRNavarro X, Sutherland ED.Neuropathy profile of diabetic patients in a pancreas transplantation program. Neurology1995;45:773–80.
14.
14. Luft D.Praxisleitfaden der diabetischen Polyneuropathie.1. Auflage. UNI-MED Verlag, Bremen2000.
16. Gerritsen JDekker JM, TenVoorde BJet al.Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease. The HOORN Study. Diabetes Care2001;24:1793–8.
17.
17. Navarro XKennedy WR, Aeppli Det al.Neuropathy and mortality in diabetes: influence of pancreas transplantation. Muscle Nerve1996;19:1009–16.
18.
18. Katz ALiberty IF, Porath Aet al.A simple bedside test of 1-minute heart rate variability during deep breathing as a prognostic index after myocardial infarction. Am Heart J1999;138:32–8.
19.
19. Valensi PSachs RN, Harfouche Bet al.Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. Diabetes Care2001;24:339–43.
20.
20. O'Brien IA, O'Hare JP, Lewin IGet al.The prevalence of autonomic neuropathy in insulin-dependent diabetes mellitus: a controlled study based on heart rate variability. Q J Med1986;61:957–67.
22. Maser REPfeifer MA, Dorman JSet al.Diabetic autonomic neuropathy and cardiovascular risk. Pittsburgh Epidemiology of Diabetes Complications Study III. Arch Intern Med1990;150:1218–22.
23.
23. Cohen JAJeffers BW, Faldut Det al.Risks for sensorimotor peripheral neuropathy and autonomic neuropathy in non-insulin-dependent diabetes mellitus (NIDDM). Muscle Nerve1998;21:72–80.
24.
24. Spallone VMaiello MR, Cicconetti Eet al.Autonomic neuropathy and cardiovascular risk factors in insulin-dependent and non-insulin-dependent diabetes. Diabetes Res Clin Pract1997;34:169–79.
25.
25. Colhoun HMFrancis DP, Rubens MBet al.The association of heart-rate variability with cardiovascular risk factors and coronary artery calcification: A study in type 1 diabetic patients and the general population. Diabetes Care2001;24:1108–14.
26.
26. Simonson DC.Etiology and prevalence of hypertension in diabetic patients. Diabetes Care1988;11:812–27.
27.
27. Muller JETofler GH, Stone HP.Circadian variation and triggers of onset of acute cardiovascular disease. Circulation1989;79:733–43.
28.
28. The Task Force of the European Society of Cardiology and the North American Society of Pacing Electrophysiology [ESC and NASPE].Heart rate variability – standards of measurement, physiological interpretation and clinical use. Circulation1996;93:1043–65.
29.
29. Esperer HD.Physiologische Grundlagen und pathologische Aspekte der Herzfrequenzvariabilität beim Menschen. Herzschr Elektrophys1994;5(suppl 2):1–10.
30.
30. Karemaker JMLie IK.Heart rate variability: a telltale of health or disease. Editorial. Eur Heart J2000;21:435–7.
31.
31. Cheng TO.Decreased heart rate variability as a predictor for sudden death was known in China in the third century A.D. Letter to the editor. Eur Heart J2000;21:2081–2.
32.
32. Scherer P.Parameter der Herzfrequenzvariabilität im Zeitbereich. Herzschr Elektrophys1994;5:15–18.
33.
33. Ewing DJMartyn CN, Young RJet al.The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care1985;8(suppl 2):491–8.
34.
34. Meesmann MBoese J, Scharf R.Vergleich der Methoden zur Bestimmung der Herzfrequenzvariabilität. Herzschr Elektrophys1994;5(suppl 2):25–9.
35.
35. Wegschneider K.Statistische Zeitreihenmodelle und Herzfrequenzvariabilität. Herzschr Elektrophys1994;5(suppl 2):11–14.
36.
36. Walbrecht PCohen JR.Estimation of heart rate power spectrum bands from real-world data: dealing with ectopic beats and noisy data. Comput Cardiol1988;15:311–14.
37.
37. Howorka KPumprla J, Schabmann A.Optimal parameters of short-term heart rate spectrogram for routine evaluation of diabetic cardiovascular autonomic neuropathy. J Auton Nerv Syst1998;69:104–72.
38.
38. Bigger JT Jr, Fleiss JL, Rolnitzky LMet al.Stability over time of heart period variability in patients with previous myocardial infarction and ventricular arrhythmias. The CAPS and ESVEM investigators. Am J Cardiol1992;69:718–23.
39.
39. Akselrod SGordon D, Ubel FAet al.Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science1981;213:220–2.
40.
40. Pomeranz BMacaulay RJ, Caudill MAet al.Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol1985;248:H151–H153.
41.
41. Rimoldi OPierini S, Ferrari Aet al.Analysis of short-term oscillations of R-R and arterial pressure in conscious dogs. Am J Physiol1990;258:H967–H976.
42.
42. Montano NRuscone TG, Porta Aet al.Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. Circulation1994;90:1826–31.
43.
43. Hayano JSakakibara Y, Yamada Aet al.Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am J Cardiol1991;67:199–204.
44.
44. Malliani APagani M, Lombardi Fet al.Cardiovascular neural regulation explored in the frequency domain. Circulation1991;84:1482–92.
45.
45. Hedman AETahvanainen KU, Hartikainen JEet al.Effect of sympathetic modulation and sympatho-vagal interaction on heart rate variability in anaesthetized dogs. Acta Physiol Scand1995;155:205–14.
46.
46. Pagani MLombardi F, Guzzetti Set al.Power spectral density of heart rate variability as an index of sympatho-vagal interaction in normal and hypertensive subjects. J Hypertens1984;2(suppl):S383–S385.
47.
47. Kamath MVGhista DN, Fallen ELet al.Heart rate variability power spectrogram as a potential non-invasive signature of cardiac regulatory system response, mechanisms, and disorders. Heart Vessels1987;3:33–41.
48.
48. Sroka K.Vagale Depression und ischämische Herzkrankheit. Herz Kreisl1998;30:437–43.
49.
49. Brüggemann T, Weiß D, Andresen D.Spektralanalyse zur Beurteilung der Herzfrequenzvariabilität. Herzschr Elektrophys1994;5(suppl 2): 19–24.
50.
50. Bigger JT Jr, Fleiss JL, Steinman RCet al.Frequency domain measures of heart period variability and mortality after myocardial infarction. Circulation1992;85:164–71.
51.
51. Tsuji HVenditti Jr FJ, Manders ESet al.Reduced heart rate variability and mortality risk in an elderly cohort. Circulation1994;90:878–83.
53. Rathmann WZiegler D, Jahnke Met al.Mortality in diabetic patients with cardiovascular autonomic neuropathy. Diabet Med1993;10:664–71.
54.
54. Wolf MMVarigos GA, Hunt Det al.Sinus arrhythmia in acute myocardial infarction. Med J Aust1978;2:52–3.
55.
55. Nolan JBatin PD, Andrews Ret al.Results of the United Kingdom Heart Failure Evaluation and Assessment of Risk Trial (UK-Heart). Circulation1998;98:1510–16.
56.
56. Kleiger REMiller JP, Bigger JT Jret al.Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol1987;59:256–62.
57.
57. Malik MFarrell T, Cripps Tet al.Heart rate variability in relation to prognosis after myocardial infarction: selection of optimal processing techniques. Eur Heart J1989;10:1060–74.
58.
58. Cripps TRMalik M, Farrell TGet al.Prognostic value of reduced heart rate variability after myocardial infarction: clinical evaluation of a new analysis method. Br Heart J1991;65:14–19.
59.
59. La Rovere MT, Bigger JT Jr, Marcus FIet al.Baroreflex sensitivity and heartrate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet1998;351:478–84.
60.
60. Ponikowski PAnker SD, Chua TPet al.Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol1997;79:1645–50.
61.
61. Makikallio THHuikuri HV, Hintze Uet al.Fractal analysis and time and frequency-domain measures of heart rate variability as predictors of mortality in patients with heart failure. Am J Cardiol2001;87:178–82.
62.
62. Klingenheben TCredner S, Grönefeld Get al.Kardialer autonomer Tonus zur Risikostratifikation nach Myokardinfarkt: Ergebnisse einer prospektiven Langzeitstudie bei 411 konsekutiven Patienten. Z Kardiol1999;88:400–09.
63.
63. De Ferrari GM, Vanoli E, Curcuruto Pet al.Prevention of life-threatening arrhythmias by pharmacologic stimulation of the muscarinic receptors with oxotremorine. Am Heart J1992;124:883–90.
64.
64. Gold DRLitonjua A, Schwartz Jet al.Ambient pollution and heart rate variability. Circulation2000;101:1267–73.
65.
65. Roche FGaspoz JM, Court-Fortune Iet al.Screening of obstructive sleep apnea syndrome by heart rate variability analysis. Circulation1999;100:1411–15.
66.
66. Kazuma NOtsuka K, Matsuoka Iet al.Heart rate variability during 24 hours in asthmatic children. Chronobiol Int1997;14:597–606.
67.
67. Coelho LSaraiva S, Guimaraes Het al.Autonomic function in chronic liver disease assessed by Heart Rate Variability Study. Rev Port Cardiol2001;20:25–36.
68.
68. Leicht ASAllen GD, Hoey JA.Influence of intensive cycling training on heart rate variability during rest and exercise. Can J Appl Physiol2003;28:898–909.
69.
69. Garet MTournaire N, Roche Fet al.Individual interdependence between nocturnal ANS activity and performance in swimmers. Med Sci Sports Exerc2004;36:2112–18.
70.
70. Agelink MWMalessa R, Baumann Bet al.Standardised tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate. Clin Auton Res2001;11:99–108.
71.
71. Ziegler DLaux G, Dannehl Ket al.Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses. Diabet Med1992;9:166–75.
72.
72. Evans JMZiegler MG, Patwardhan ARet al.Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes. J Appl Physiol2001;91:2611–18.
73.
73. Wawryk AMBates DJ, Couper JJ.Power spectral analysis of heart rate variability in children and adolescents with IDDM. Diabetes Care1997;20:1416–21.
74.
74. Ziegler DGries FA, Spüler Met al.The epidemiology of diabetic neuropathy. Diabetic Cardiovascular Autonomic Neuropathy Multicenter Study Group. J Diabetes Complications1992;6:49–57.
75.
75. Chessa MButera G, Lanza GAet al.Role of heart rate variability in the early diagnosis of diabetic autonomic neuropathy in children. Herz2002;27:785–90.
76.
76. Levitt NSStansberry KB, Wynchank Set al.The natural progression of autonomic neuropathy and autonomic function tests in a cohort of people with IDDM. Diabetes Care1996;19:751–4.
77.
77. Howorka KPumprla J, Haber Pet al.Effects of physical training on heart rate variability in diabetic patients with various degrees of cardiovascular autonomic neuropathy. Cardiovasc Res1997;34:206–14.
78.
78. Singh JPLarson MG, O'Donnell CJet al.Association of hyperglycemia with reduced heart rate variability (The Framingham Heart Study). Am J Cardiol2000;86:309–12.
79.
79. DCCT Research Group.The absence of a glycemic threshold for the development of long-term complications: the perspective of the Diabetes Control and Complications Trial (DCCT). Diabetes1996;45:1289–98.
80.
80. Gaede PVedel P, Larsen Net al.Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med2003;348:383–93.
81.
81. Ziegler DSchatz H, Conrad Fet al.Effects of treatment with the antioxidant α-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Diabetes Care1997;20:369–73.
82.
82. Didangelos TPKaramitsos DT, Athyros VGet al.Effect of aldose reductase inhibition on cardiovascular reflex tests in patients with definite diabetic autonomic neuropathy over a period of 2 years. J Diabetes Complications1998;12:201–07.
83.
83. Okamoto HNomura M, Nakaya Yet al.Effects of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy and gastroparesis. Intern Med2003;42:655–64.
84.
84. Kontopoulos AGAthyros VG, Didangelos TPet al.Effect of chronic quinapril administration on heart rate variability in patients with diabetic autonomic neuropathy. Diabetes Care1997;20:355–61.
85.
85. Malik RAWilliamson S, Abbott Cet al.Effect of angiotensin-converting-enzyme (ACE) inhibitor trandolapril on human diabetic neuropathy: randomised double-blind controlled trial. Lancet1998;352:1978–81.
86.
86. Ebbehoj EPoulsen PL, Hansen KWet al.Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in type I diabetic patients with abnormal albuminuria. Diabetologia2002;45:965–75.
87.
87. Gaede Psecond author, third authoret al.Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med2008;358:580–58.
88.
88. Tesfaye SChaturvedi N, Eaton SEMet al.Vascular risk factors and diabetic neuropathy. N Engl J Med2005;352:341–50.
89.
89. Schönauer M, Schreiner M, Niebauer Jet al.Einfluss der Stoffwechselverbesserung unter Pioglitazon auf die Herzfrequenzvariabilität bei Typ-2-Diabetikern: Ergebnisse der Praxisstudie ETAPP. Dtsch Ärztebl Thüringen2004;15:340–1.
90.
90. Kautz, C, Thomas A.Kardiale autonome diabetische Neuropathie. Diabetologie Stoffwechsel2007;2:175–82.
91.
91. Eiskjar NWeston P J, Bush Get al.A pocket size device to detect autonomic neuropathy. J Diabetes Sci Technol2008;4:692–6.
92.
92. Boulton AJMVinik AI, Arezzo JCet al.Diabetic neuropathies, A statement by the American Diabetes Association. Diabetes Care2005;28:956–62.