Skip to main content

Advertisement

SpringerLink
Log in

An update on autonomic neuropathy affecting the gastrointestinal tract

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Gastrointestinal symptoms and disordered gut motility occur frequently in the diabetic population and are generally regarded as manifestations of gastrointestinal "autonomic dysfunction," although the relationships between both symptoms and dysmotility with abnormal cardiovascular autonomic function are weak. It is now recognized that the blood glucose concentration is both a determinant of and determined by gastrointestinal function. An improved de.nition of the underlying pathophysiology should facilitate the development of therapies that are targeted more effectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Forster J, Damjanov I, Lin Z, et al.: Absence of the interstitial cells of Cajal in patients with gastroparesis and correlation with clinical findings. J Gastrointest Surg 2005, 2:588–590. An important study identifying the potential role of the ICC in diabetic gastroparesis. Full-thickness antral wall biopsies were obtained from 14 gastroparetic patients at the time of surgery for gastric electrical stimulation. A reduction or absence in the number of ICC was evident in a subset of patients, which correlated with greater motility disturbance, more symptoms, and a poorer response to therapy.

    Google Scholar 

  2. Smout AJ: Oesophageal function. In Gastrointestinal Function in Diabetes Mellitus. Edited by Horowitz M, Samsom M. Chichester: John Wiley and Sons; 2004:97–116.

    Chapter  Google Scholar 

  3. Horowitz M, Dent J, Fraser R, et al.: Role and integration of mechanisms controlling gastric emptying. Dig Dis Sci 1994, 39:S7-S13.

    Article  Google Scholar 

  4. Horowitz M, Jones KL, Akkermans LMA, Samson M: Gastric function. In Gastrointestinal Function in Diabetes Mellitus. Edited by Horowitz M, Samsom M. Chichester: John Wiley and Sons; 2004:117–176.

    Chapter  Google Scholar 

  5. Horowitz M, Edelbroek M, Wishart JM, Straathof JW: Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia 1993, 36:857–862.

    Article  PubMed  CAS  Google Scholar 

  6. Samson M, Verhagen M: Intestinal function. In Gastrointestinal Function in Diabetes Mellitus. Edited by Horowitz M, Samsom M. Chichester: John Wiley and Sons; 2004:177–217.

    Chapter  Google Scholar 

  7. Sun WS, Read N: Anorectal function. In Gastrointestinal Function in Diabetes Mellitus. Edited by Horowitz M, Samsom M. Chichester: John Wiley and Sons; 2004:219–246.

    Chapter  Google Scholar 

  8. Hammer J, Abell T, Cutts T, Talley NJ. Epidemiology of disordered gastrointestinal function and impact of chronic gastrointestinal symptoms on quality of life. In Gastrointestinal Function in Diabetes Mellitus. Edited by Horowitz M, Samsom M. Chichester: John Wiley and Sons; 2004:1–27.

    Chapter  Google Scholar 

  9. Bytzer PM, Talley NJ, Hammer J, et al.: Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,0000 adults. Arch Intern Med 2000, 161:1989–1996.

    Article  Google Scholar 

  10. Enck P, Rathmann W, Spiekermann M, et al.: Prevalence of gastrointestinal symptoms in diabetic patients and nondiabetic subjects. Z Gastroenterol 1994, 32:637–641.

    PubMed  CAS  Google Scholar 

  11. Low PA, Benrud-Lason LM, Sletten DM, et al.: Autonomic symptoms and diabetic neuropathy. A population-based study. Diabetes Care 2004, 27:2942–2947.

    Article  PubMed  Google Scholar 

  12. Vinik AI, Maser RE, Mitchell BD, Freeman R: Diabetic autonomic neuropathy. Diabetes Care 2003, 26:1553–1579. A comprehensive review of autonomic neuropathy in diabetes, focusing largely on cardiovascular autonomic neuropathy, but with a concise summary of autonomic neuropathy involving the GI tract.

    Article  PubMed  Google Scholar 

  13. Young AA, Edwards GL: Effects of diabetes mellitus on gastrointestinal function in animal models. In Gastrointestinal Function in Diabetes Mellitus. Edited by Horowitz M, Samsom M. Chichester: John Wiley and Sons; 2004:29–95.

    Chapter  Google Scholar 

  14. Ordog T, Takayama I, Cheung WK, et al.: Remodelling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis. Diabetes 2000, 49:19731–19739.

    Article  Google Scholar 

  15. Horvath VJ, Vittal H, Lorincz A, et al.: Reduced stem cell factor links smooth myopathy and loss of interstitial cells of Cajal in murine diabetic gastroparesis. Gastroenterology 2006, 130:759–770.

    Article  PubMed  CAS  Google Scholar 

  16. Shotton HR, Lincoln J: Diabetes only affects nitric oxide synthase-containing myenteric neurons that do not contain heme oxygenase 2. Brain Res 2006, 1068:248–256.

    Article  PubMed  CAS  Google Scholar 

  17. Anitha M, Gondha C, Sutliff R, et al.: GDNF rescues hyperglycaemia-induced diabetic enteric neuropathy through activation of the P13/Akt pathway. J Clin Invest 2006, 116:344–356.

    Article  PubMed  CAS  Google Scholar 

  18. Yoshida MM, Schuf.er MD, Sumi SM: There are no morphologic abnormalities of the gastric wall or abdominal vagus in patients with diabetic gastroparesis. Gastroenterology 1988, 94:907–914.

    PubMed  CAS  Google Scholar 

  19. Gilbey SG, Guy RJ, Jones H, et al.: Diabetes and autonomic neuropathy: an immunological association? Diabet Med 1986, 3:241–245.

    Article  PubMed  CAS  Google Scholar 

  20. Granberg V, Ejskjaer N, Peakman M, Sunkvist G: Autoantibodies to autonomic nerves associated with cardiac and peripheral autonomic neuropathy. Diabetes Care 2005, 28:1959–1964.

    Article  PubMed  Google Scholar 

  21. Jackson MW, Gordon TP, Waterman SA: Disruption of intestinal motility by a calcium channel-stimulating autoantibody in type 1 diabetes. Gastroenterology 2004, 126:819–828.

    Article  PubMed  CAS  Google Scholar 

  22. He CL, Soffer EE, Ferris CD, et al.: Loss of interstitial cells of Cajal and inhibitory innervation in insulin-dependent diabetes. Gastroenterology 2001, 121:427–434.

    Article  PubMed  CAS  Google Scholar 

  23. 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 

  24. Rayner CK, Jones KL, Samsom M, Horowitz M: Relationships of upper gastrointestinal motor and sensory function with glycaemic control. Diabetes Care 2001, 24:371–381.

    Article  PubMed  CAS  Google Scholar 

  25. Fraser RJ, Horowitz M, Maddox AF, et al.: Hyperglycaemia slows gastric emptying in type 1 insulin-dependent diabetes mellitus. Diabetologia 1990, 30:675–680.

    Article  Google Scholar 

  26. Schvarcz E, Palmer M, Aman J, et al.: Physiological hyperglycaemia slows gastric emptying in normal subjects and subjects with insulin-dependent diabetes mellitus. Gastroenterology 1997, 113:60–66.

    Article  PubMed  CAS  Google Scholar 

  27. Russo A, Stevens JE, Chen R, et al.: Insulin-induced hypoglycemia accelerates gastric emptying of solids and liquids in long-standing type 1 diabetes. J Clin Endocrinol Metab 2005, 90:4489–4495.

    Article  PubMed  CAS  Google Scholar 

  28. Maximilian B, Barnert J, Wienbeck M: Autonomic dysfunction and gastrointestinal tract. Clin Auton Res 1999, 9:75–81.

    Article  Google Scholar 

  29. Ewing DJ, Martyn CN, Young RJ, Clarke BF: The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 1985, 8:491–498.

    Article  PubMed  CAS  Google Scholar 

  30. Phillips WT, Schwartz JG, McMahan CA: Rapid gastric emptying of an oral glucose solution in type 2 diabetic patients. J Nucl Med 1992, 33:1496–1500.

    PubMed  CAS  Google Scholar 

  31. Jones KL, Horowitz M, Carney BJ, et al.: Gastric emptying in early non insulin-dependent diabetes mellitus. J Nucl Med 1996, 37:1643–1648.

    PubMed  CAS  Google Scholar 

  32. Rayner C, Horowitz M: New management approaches for gastroparesis. Nat Clin Pract Gastroenterol Hepatol 2005, 2:454–462.

    Article  PubMed  Google Scholar 

  33. Jones KL, Russo A, Stevens JE, et al.: Predictors of delayed gastric emptying in diabetes. Diabetes Care 2001, 24:1264–1269.

    Article  PubMed  CAS  Google Scholar 

  34. Horowitz M, Harding PE, Chatterton BE, et al.: Acute and chronic effect of domperidone on gastric emptying in diabetic autonomic neuropathy. Dig Dis Sci 1985, 30:1–9.

    Article  PubMed  CAS  Google Scholar 

  35. Farup CE, Leidy NY, Murray M, et al.: Effect of domperidone on the health-related quality of life of patients with symptoms of diabetic gastroparesis. Diabetes Care 1998, 21:1699–1706.

    Article  PubMed  CAS  Google Scholar 

  36. Abell TL, Bernstein RK, Cutts T, et al.: Treatment of gastroparesis: a multidisciplinary clinical review. The American Motility Task Force on Gastroparesis. Neurogastroenterol Motil 2006, 18:263–283. An excellent overview of the current approach to the management of gastroparesis, including summaries of new and emerging therapies.

    Article  PubMed  CAS  Google Scholar 

  37. Jones KL, Berry M, Kong MF, et al.: Hyperglycaemia attenuates the gastrokinetic effect of erythromycin and affects the perception of postprandial hunger in normal subjects. Diabetes Care 1999, 22:339–344.

    Article  PubMed  CAS  Google Scholar 

  38. Janssens J, Peeters TL, Vantrappen G, et al.: Erythromycin improves delayed gastric emptying in diabetic gastroparesis. N Engl J Med 1990, 332:1028–1031.

    Article  Google Scholar 

  39. Maganti K, Onyemere K, Jones MP: Oral erythromycin and symptomatic relief of gastroparesis: a systemic review. Am J Gastroenterol 2003, 98:259–263.

    PubMed  CAS  Google Scholar 

  40. McHugh S, Lico S, Diamant NE: Cisapride vs metoclopramide. An acute study in diabetic gastroparesis. Dig Dis Sci 1992, 37:997–1001.

    Article  PubMed  CAS  Google Scholar 

  41. Melga P, Mansi C, Ciuchi E, et al.: Chronic administration of levosulpiride and glycaemic control in IDDM patients with gastroparesis. Diabetes Care 1997, 20:55–58.

    Article  PubMed  CAS  Google Scholar 

  42. Asawaka H, Hayashi I, Fukui T, Tokunga K: Effects of mosapride on glycaemic control and gastric emptying in type 2 diabetes mellitus patients with gastropathy. Diabetes Res Clin Pract 2003, 61:175–182.

    Article  CAS  Google Scholar 

  43. Murray CD, Martin NM, Patterson M, et al.: Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study. Gut 2005, 54:1693–1698. This is a double-blind, placebo-controlled, crossover study in 10 diabetic patients requiring insulin. In response to a 2-hour infusion of ghrelin in the context of a euglycemic clamp, gastric emptying as assessed by ultrasound was accelerated in seven of 10 subjects. Ghrelin-based therapies may potentially represent a novel prokinetic class.

    Article  PubMed  CAS  Google Scholar 

  44. Park MI, Ferber M, Camilleri K, et al.: Effect of atilmotin on gastrointestinal transit in healthy subjects: a randomized, placebo-controlled study. Neurogastroenterol Motil 2006, 18:28–36.

    Article  PubMed  Google Scholar 

  45. McCallum RW, Rogel R, Fang JC, et al.: Mitemacil fumarate (GM-611) provided symptomatic relief of diabetic gastroparesis, especially in type 1 diabetics: results of a 12-week, multi-centre, double-blind, placebo controlled, randomized phase 2b study. Gastroenterology 2005, 128:A467.

    Google Scholar 

  46. Dishy V, Cohen Pour M, Feldman L, et al.: The effect of sildenafil on gastric emptying in patients with end-stage renal failure and symptoms of gastroparesis. Clin Pharm Ther 2004, 76:281–286.

    Article  CAS  Google Scholar 

  47. Stevens JE, Russo A, Delaney CA, et al.: Acute effects of C-peptide on gastric emptying in longstanding type 1 diabetes. Clin Auton Res 2006, 16:55–57.

    Article  PubMed  Google Scholar 

  48. Gaber AO, Oxley D, Karas J, et al.: Changes in gastric emptying in recipients of successful combined pancreaskidney transplants. Dig Dis 1991, 9:437–443.

    Article  PubMed  CAS  Google Scholar 

  49. Lacy BE, Zayat EN, Crowell MD, Schuster MM: Botulinum toxin for the treatment of gastroparesis: a preliminary report. Am J Gastroenterol 2002, 97:1548–1552.

    Article  PubMed  CAS  Google Scholar 

  50. Lacy BE, Weiser K: Gastric motility, gastroparesis, and gastric stimulation. Surg Clin North Am 2005, 85:967–987.

    Article  PubMed  Google Scholar 

  51. Forster J, Sarosiek I, Delcore R, et al.: Gastric pacing is a new surgical treatment for gastroparesis. Am J Surg 2001, 182:676–681.

    Article  PubMed  CAS  Google Scholar 

  52. Forster J, Sarosiek I, Lin Z, et al.: Further experience with gastric stimulation to treat refractory gastroparesis. Am J Surg 2003, 186:690–695.

    Article  PubMed  Google Scholar 

  53. Abell T, McCallum R, Hocking M, et al.: Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology 2003, 125:421–428.

    Article  PubMed  Google Scholar 

  54. Lin Z, Sarosiek I, Forster J, McCallum RW: Symptom responses, long-term outcomes and adverse events beyond 3 years of high-frequency gastric electrical stimulation for gastroparesis. Neurogastroenterol Motil 2006, 18:18–27. This study provides the most comprehensive follow-up of patients receiving gastric electrical stimulation. Data were collected at baseline, 1 year, and beyond 3 years in 55 patients (39 with diabetes). An improvement in symptom score and glycemic control, as well as a reduction in hospitalization and prokinetic medications, was seen. The study was uncontrolled.

    Article  PubMed  CAS  Google Scholar 

  55. Abell T, Al-Juburi A, Bashed H, Miroch A: 13 years, 214 patients and over 5000 patient months: a long term report on gastric electric stimulation. Gastroenterology 2005, 50:1328–1334.

    Google Scholar 

  56. Lin Z, Forster J, Sarosiek I, McCallum RW: Treatment of diabetic gastroparesis by high-frequency nerve stimulation. Diabetes Care 2004, 27:1071–1076.

    Article  PubMed  Google Scholar 

  57. Horowitz M, Jones KL, Rayner CK, Read NW: "Gastric" hypoglycaemia—an important concept in diabetes management. Neurogastroenterol Motil 2006, 18:405–407.

    Article  PubMed  CAS  Google Scholar 

  58. Gallwitz B: Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. Treat Endocrinol 2005, 4:361–370.

    Article  PubMed  CAS  Google Scholar 

  59. Meier JJ, Kemmeries G, Holst JJ, et al.: Erythromycin antagonises the deceleration of gastric emptying by glucagon-like-peptide-1 and unmasks its insulinotropic effect in healthy subjects. Diabetes 2005, 54:2212–2218.

    Article  PubMed  CAS  Google Scholar 

  60. Battle WM, Snape WJ Jr, Alavi A, et al.: Colonic dysfunction in diabetes mellitus. Gastroenterology 1980, 79:1217–1221.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, 5000, North Terrace, Adelaide, South Australia, Australia

    Michael Horowitz MBBS, PhD, FRACP

Authors
  1. Liza K. Phillips MBBS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher K. Rayner MBBS, PhD, FRACP
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karen L. Jones Dip App Sci, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Horowitz MBBS, PhD, FRACP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Horowitz MBBS, PhD, FRACP.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Phillips, L.K., Rayner, C.K., Jones, K.L. et al. An update on autonomic neuropathy affecting the gastrointestinal tract. Curr Diab Rep 6, 417–423 (2006). https://doi.org/10.1007/s11892-006-0073-0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-006-0073-0

Keywords

Search

Navigation