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Diagnosis and treatment of diabetic autonomic neuropathy

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Abstract

Diabetic autonomic neuropathy (DAN) is associated with a markedly reduced quality of life and poor prognosis. The manifestations of DAN cause multiple symptoms and involve the 1) cardiovascular system: resting tachycardia, reduced heart rate variability and circadian rhythm of heart rate and blood pressure, painless myocardial ischemia/ infarction, orthostatic hypotension, exercise intolerance, perioperative instability, sudden death; 2) respiratory system: reduced ventilatory drive to hypercapnia/ hypoxemia, sleep apnea; 3) gastrointestinal tract: esophageal motor dysfunction, diabetic gastroparesis, gallbladder atony, diabetic enteropathy, colonic hypomotility, anorectal dysfunction; and 4) genitourinary tract: diabetic cystopathy, erectile dysfunction.

Treatment is based on four cornerstones: 1) causal treatment aimed at near-normoglycemia; 2) treatment based on pathogenetic mechanisms; 3) symptomatic treatment; and 4) avoidance of risk factors and complications. Pharmacologic treatment of symptomatic DAN may be difficult, due to limited efficacy and frequent adverse reactions. First-line treatments include midodrine for orthostatic hypotension, prokinetic drugs for gastroparesis, broad-spectrum antibiotics for diabetic diarrhea, and sildenafil for erectile dysfunction. Prior to an adequate symptomatic treatment a thorough risk-benefit estimate, aimed at maintaining the patient’s quality of life, is required.

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References and Recommended Reading

  1. Rundles RW: Diabetic neuropathy. General review with report of 125 cases. Medicine (Baltimore) 1945, 24:111–160.

    Google Scholar 

  2. Ewing DJ, Clarke BF: Diabetic autonomic neuropathy: present insights and future prospects. Diabetes Care 1986, 9:648–665.

    PubMed  CAS  Google Scholar 

  3. Consensus statement: Report and recommendations of the San Antonio conference on diabetic neuropathy. American Diabetes Association American Academy of Neurology [no authors listed]. Diabetes Care 1988, 11:592–597.

  4. Kahn R: Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Autonomic nervous system testing. Diabetes Care 1992, 15(suppl 3):1095–1103.

    PubMed  CAS  Google Scholar 

  5. Ziegler D: Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis, and treatment. Diab Metab Rev 1994, 10:339–383.

    CAS  Google Scholar 

  6. Hendrickse MT, Thuluvath PJ, Triger DR: Natural history of autonomic neuropathy in chronic liver disease. Lancet 1992, 339:1462–1464.

    Article  PubMed  CAS  Google Scholar 

  7. Whitsel EA, Boyko EJ, Siscovick DS: Reassessing the role of QTc in the diagnosis of autonomic failure among patients with diabetes. A meta-analysis. Diabetes Care 2000, 23:241–247.

    Article  PubMed  CAS  Google Scholar 

  8. Veglio M, Sivieri R, Chinaglia A, et al.: QT interval prolongation and mortality in type 1 diabetic patients. A 5-year cohort prospective study. Diabetes Care 2000, 23:1381–1383. This is the first cohort-based prospective study indicating that QTc prolongation is an important predictor of mortality in type 1 diabetic patients. Measurement of the QTc interval is an easy, simple, and inexpensive test that could be used to stratify the risk of mortality in diabetic patients.

    Article  PubMed  CAS  Google Scholar 

  9. Neil HAW, Thompson AV, John S, et al.: Diabetic autonomic neuropathy: the prevalence of impaired heart rate variability in a geographically defined population. Diabet Med 1989, 6:20–24.

    Article  PubMed  CAS  Google Scholar 

  10. Ziegler D, Gries FA, Mühlen H, et al., and the DiaCAN Multicenter Study Group: Prevalence of cardiovascular autonomic and peripheral diabetic neuropathy in patients attending diabetes centers. Diabet Metab 1993, 19:143–151.

    CAS  Google Scholar 

  11. Stephenson J, Fuller JH, EURODIAB IDDM Complications Study Group: Microvascular and acute complications in IDDM patients: the EURODIAB IDDM Complications Study. Diabetologia 1994, 37:278–285.

    Article  Google Scholar 

  12. Colhoun HM, Francis DP, Rubens MB, et al.: The association of heart-rate variability with cardiovascular risk factors and coronary artery calcification. Diabetes Care 2001, 24:1108–1114. Shows that in type 1 diabetic patients without a history of cardiovascular disease, reduced HRV clusters with other cardiovascular risk factors, particularly those that are more common in the insulin resistance syndrome.

    Article  PubMed  CAS  Google Scholar 

  13. Canto JG, Shlipak MG, Rogers WJ, et al.: Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. JAMA 2000, 283:3223–3229. This large prospective observational study shows that the frequency of patients presenting without chest pain at the time of diagnosis of myocardial infarction is relatively high, being even higher in diabetic patients. The lack of chest pain in diabetic patients with myocardial infarction may be due to autonomic neuropathy, which might be responsible for an increased risk for delays in seeking medical attention, less aggressive treatment, and in-hospital mortality.

    Article  PubMed  CAS  Google Scholar 

  14. Valensi P, Sachs R-N, Harfouche B, et al.: Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. Diabetes Care 2001, 24:339–343. Emphasizes the importance of CAN as a predictor of major cardiac events in asymptomatic diabetic patients. Hence, to detect asymptomatic myocardial ischemia at an early stage, screening for CAN should include as many diabetic patients with cardiovascular risk factors as possible.

    Article  PubMed  CAS  Google Scholar 

  15. Ambepityia G, Kopelman PG, Ingram D, et al.: Exertional myocardial ischemia in diabetes: a quantitative analysis of anginal perceptual threshold and the influence of autonomic function. J Am Coll Cardiol 1990, 15:72–77.

    Article  PubMed  CAS  Google Scholar 

  16. Airaksinen KEJ: Silent coronary artery disease in diabetes— a feature of autonomic neuropathy or accelerated atherosclerosis? Diabetologia 2001, 44:259–266. In this provocative review the role of CAN in asymptomatic coronary artery disease is being questioned. It is argued that there is no convincing clinical or epidemiologic evidence that CAN plays a major part in the lack of ischemic chest pain.

    Article  PubMed  CAS  Google Scholar 

  17. Kitamura A, Hoshino T, Kon T, Ogawa R: Patients with diabetic neuropathy are of risk of a greater intraoperative reduction in core temperature. Anesthesiology 2000, 92:1311–1218.

    Article  PubMed  CAS  Google Scholar 

  18. Genovely H, Pfeifer MA: RR-variation: the autonomic test of choice in diabetes. Diabetes Metab Rev 1988, 3:255–271.

    Google Scholar 

  19. Ziegler D, Piolot R: Evaluation of statistical, geometric, frequency domain, and nonlinear measures of 24-hour heart rate variability in diabetic patients with various degrees of cardiovascular autonomic neuropathy. Clin Auton Res 1998, 8:282–283.

    Google Scholar 

  20. Cameron NE, Cotter MA: The relationship of vascular changes to metabolic factors in diabetes mellitus and their role in the development of peripheral nerve complications. Diab Metab Rev 1994, 10:189–224.

    CAS  Google Scholar 

  21. Ziegler D, Schatz H, Conrad F, et al., the DEKAN Study Group: Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Diabetes Care 1997, 20:369–373.

    Article  PubMed  CAS  Google Scholar 

  22. Kontopoulos AG, Athyros VG, Didangelos TP, et al.: Effect of chronic quinapril administration on heart rate variability in patients with diabetic autonomic neuropathy. Diabetes Care 1997, 20:355–361.

    Article  PubMed  CAS  Google Scholar 

  23. Aronson D: Pharmacologic modulation of autonomic tone: implications for the diabetic patient. Diabetologia 1997, 40:476–481.

    Article  PubMed  CAS  Google Scholar 

  24. Jankovic J, Gilden JL, Hiner BC, et al.: Neurogenic orthostatic hypotension: a double blind, placebo-controlled study with midodrine. Am J Med 1993, 95:38–48.

    Article  PubMed  CAS  Google Scholar 

  25. Campbell IW, Ewing DJ, Clarke BF: 9-alpha-fluorohydrocortisone in the treatment of postural hypotension in diabetic autonomic neuropathy. Diabetes 1975, 24:381–384.

    Article  PubMed  CAS  Google Scholar 

  26. Watkins PJ: Facial sweating after food: a new sign of diabetic autonomic neuropathy. BMJ 1973, 1:583–587.

    Article  PubMed  CAS  Google Scholar 

  27. Shaw JE, Parker R, Hollis S, et al.: Gustatory sweating in diabetes mellitus. Diabet Med 1996, 13:1033–1037.

    Article  PubMed  CAS  Google Scholar 

  28. Shaw JE, Abbott CA, Tindle K, et al.: A randomized controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweating. Diabetologia 1997, 40:299–301.

    Article  PubMed  CAS  Google Scholar 

  29. Fraser R, Michell G, Horowitz M: Gastrointestinal motor dysfunction in diabetes mellitus. Diabetes Rev Int 1994, 3:9–12.

    Google Scholar 

  30. Kong MS, Macdonald IA, Tattersall RB: Gastric emptying in diabetes mellitus. Diabet Med 1996, 13:112–119.

    Article  PubMed  CAS  Google Scholar 

  31. Rathmann W, Enck P, Ziegler D: Gastrointestinale Funktionsstörungen bei autonomer Neuropathie: Aktuelle Aspekte zur Diagnostik und Therapie. Nervenheilkunde 1996, 15:414–419.

    Google Scholar 

  32. Ziegler D, Schadewaldt P, Pour Mirza A, et al.: [13C] octanoic acid breath test for non-invasive assessment of gastric emptying in diabetic patients: validation and relationship to gastric symptoms and cardiovascular autonomic function. Diabetologia 1996, 39:823–830.

    Article  PubMed  CAS  Google Scholar 

  33. Ejskjaer NT, Bradley JL, Buxton-Thomas MS, et al.: Novel surgical treatment and gastric pathology in diabetic gastroparesis. Diabet Med 1999, 16:488–495.

    Article  PubMed  CAS  Google Scholar 

  34. Ogbonnaya KI, Arem R: Diabetic diarrhea. Pathophysiology, diagnosis, and management. Arch Intern Med 1990, 150:262–267.

    Article  PubMed  CAS  Google Scholar 

  35. Valdovinos MA, Camilleri M, Zimmerman BR: Chronic diarrhea in diabetes mellitus: mechanisms and an approach to diagnosis and treatment. Mayo Clin Proc 1993, 68:691–702.

    PubMed  CAS  Google Scholar 

  36. Battle WM, Cohen JD, Snape WJ: Disorders of colonic motility in patients with diabetes mellitus. Yale J Biol Med 1983, 56:277–283.

    PubMed  CAS  Google Scholar 

  37. DePonti F, Fealey RD, Malagelada J-R: Gastrointestinal syndromes due to diabetes mellitus. In Diabetic Neuropathy. Edited by Dyck PJ et al. Philadelphia: W.B. Saunders; 1987:155–161.

    Google Scholar 

  38. Bradley WE: Diagnosis of urinary bladder dysfunction in diabetes mellitus. Ann Intern Med 1980, 92:323–326.

    PubMed  CAS  Google Scholar 

  39. Kirby RS, Pryor JP: Bladder dysfunction and impotence. In Diabetic Neuropathy. Edited by Dyck PJ et al. Philadelphia: W.B. Saunders; 1987:204–207.

    Google Scholar 

  40. Frimodt-Moller C, Mortensen S: Treatment of diabetic cystopathy. Ann Intern Med 1980, 92:327–328.

    PubMed  CAS  Google Scholar 

  41. NIH Consensus Conference. Impotence. NIH development panel on impotence [no authors listed]. JAMA 1993, 270:83–90.

  42. Wagner G, Saenz de Tejada I: Update on male erectile dysfunction. BMJ 1998, 316:678–682.

    PubMed  CAS  Google Scholar 

  43. Feldman HA, Goldstein I, Hatzichristou DG, et al.: Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study. J Urol 1994, 151:54–61.

    PubMed  CAS  Google Scholar 

  44. Fedele D, Coscelli C, Santeusanio F, et al.: Erectile dysfunction in diabetic subjects in Italy. Diabetes Care 1998, 21:1973- 1977.

    Article  PubMed  CAS  Google Scholar 

  45. European Society for Impotence Research: Erectile Dysfunction: A Physicians’ Guide to the Management of Erectile Dysfunction. European Society for Impotence Research; 1998. This document gives comprehensive guidelines on how to diagnose and manage ED of various causes, including diabetes.

  46. Jovanovic L: Sex and the woman with diabetes: desire versus dysfunction. IDF Bull 1998, 43:23–28. Highlights the largely neglected area of female sexual dysfunction in diabetes.

    Google Scholar 

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  1. German Diabetes Clinic, German Diabetes Research Institute at the Heinrich Heine University, Auf’m Hennekamp 65, 40225, Düsseldorf, Germany

    Dan Ziegler MD

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  1. Dan Ziegler MD
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Ziegler, D. Diagnosis and treatment of diabetic autonomic neuropathy. Curr Diab Rep 1, 216–227 (2001). https://doi.org/10.1007/s11892-001-0037-3

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  • DOI: https://doi.org/10.1007/s11892-001-0037-3

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