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Diabetic autonomic neuropathy of the gastrointestinal tract

Thomas Frieling, MD
Section Editors
Nicholas J Talley, MD, PhD
David M Nathan, MD
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Diabetic autonomic neuropathy may involve the cardiovascular, genitourinary, and the neuroendocrine systems as well as the upper and lower gastrointestinal (GI) tract. Abnormalities of GI function in diabetics are thought to be related, at least in part, to autonomic neuropathy of the enteric nervous system.

This topic will review the GI manifestations of diabetic autonomic neuropathy. The other manifestations of diabetic autonomic neuropathy are discussed separately. (See "Diabetic autonomic neuropathy".)


Most studies assessing the prevalence of gastrointestinal GI symptoms in patients with diabetes mellitus have suggested that diabetics are more likely to experience GI symptoms as compared with controls [1-12]. Upper GI symptoms may be more common in patients with long-term type 1 diabetes mellitus [13]. However, discordant data have also been reported. The difference among studies may in part be related to the inclusion of patients with varying disease severity and/or glycemic control. Furthermore, studies have not consistently used validated measures of GI symptoms [14].

The true prevalence of gastroparesis in patients with diabetes is unknown, and prevalence estimates have varied widely [15,16]. While in early studies in tertiary medical centers, up to 60 percent of patients with longstanding type 1 diabetes mellitus and GI symptoms had diabetic gastroparesis, these studies predated the use of intensive insulin treatment [17]. In a population-based study, the 10-year incidence of symptomatic gastroparesis in patients with type 1 and 2 diabetes were 5 and 1 percent, respectively [18].

Estimates of the prevalence of diabetic diarrhea have varied widely between 8 and 22 percent [8,19]. It is likely, however, that the true incidence is substantially lower. In a population-based study, for example, no differences in the prevalence of diarrhea were detected among non-insulin-dependent diabetics, insulin-dependent diabetics, and healthy controls [12]. In another study that included 200 diabetic patients attending an outpatient clinic, only two complained of nocturnal diarrhea, both of whom had autonomic neuropathy [11].

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Literature review current through: Nov 2017. | This topic last updated: May 24, 2016.
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  1. Spångéus A, El-Salhy M, Suhr O, et al. Prevalence of gastrointestinal symptoms in young and middle-aged diabetic patients. Scand J Gastroenterol 1999; 34:1196.
  2. Ricci JA, Siddique R, Stewart WF, et al. Upper gastrointestinal symptoms in a U.S. national sample of adults with diabetes. Scand J Gastroenterol 2000; 35:152.
  3. Ko GT, Chan WB, Chan JC, et al. Gastrointestinal symptoms in Chinese patients with Type 2 diabetes mellitus. Diabet Med 1999; 16:670.
  4. Locke GR 3rd. Epidemiology of gastrointestinal complications of diabetes mellitus. Eur J Gastroenterol Hepatol 1995; 7:711.
  5. Bytzer P, Talley NJ, Hammer J, et al. GI symptoms in diabetes mellitus are associated with both poor glycemic control and diabetic complications. Am J Gastroenterol 2002; 97:604.
  6. Bytzer P, Talley NJ, Leemon M, et al. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med 2001; 161:1989.
  7. Lluch I, Ascaso JF, Mora F, et al. Gastroesophageal reflux in diabetes mellitus. Am J Gastroenterol 1999; 94:919.
  8. Feldman M, Schiller LR. Disorders of gastrointestinal motility associated with diabetes mellitus. Ann Intern Med 1983; 98:378.
  9. Clouse RE, Lustman PJ. Gastrointestinal symptoms in diabetic patients: lack of association with neuropathy. Am J Gastroenterol 1989; 84:868.
  10. Maser RE, Pfeifer MA, Dorman JS, et al. Diabetic autonomic neuropathy and cardiovascular risk. Pittsburgh Epidemiology of Diabetes Complications Study III. Arch Intern Med 1990; 150:1218.
  11. Maxton DG, Whorwell PJ. Functional bowel symptoms in diabetes--the role of autonomic neuropathy. Postgrad Med J 1991; 67:991.
  12. Janatuinen E, Pikkarainen P, Laakso M, Pyörälä K. Gastrointestinal symptoms in middle-aged diabetic patients. Scand J Gastroenterol 1993; 28:427.
  13. Schvarcz E, Palmér M, Ingberg CM, et al. Increased prevalence of upper gastrointestinal symptoms in long-term type 1 diabetes mellitus. Diabet Med 1996; 13:478.
  14. Quan C, Talley NJ, Cross S, et al. Development and validation of the Diabetes Bowel Symptom Questionnaire. Aliment Pharmacol Ther 2003; 17:1179.
  15. Parkman HP, Hasler WL, Fisher RS, American Gastroenterological Association. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology 2004; 127:1592.
  16. Parkman HP, Hasler WL, Fisher RS, American Gastroenterological Association. American Gastroenterological Association medical position statement: diagnosis and treatment of gastroparesis. Gastroenterology 2004; 127:1589.
  17. Camilleri M, Bharucha AE, Farrugia G. Epidemiology, mechanisms, and management of diabetic gastroparesis. Clin Gastroenterol Hepatol 2011; 9:5.
  18. Choung RS, Locke GR 3rd, Schleck CD, et al. Risk of gastroparesis in subjects with type 1 and 2 diabetes in the general population. Am J Gastroenterol 2012; 107:82.
  19. Dandona P, Fonseca V, Mier A, Beckett AG. Diarrhea and metformin in a diabetic clinic. Diabetes Care 1983; 6:472.
  20. Rayner CK, Samsom M, Jones KL, Horowitz M. Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care 2001; 24:371.
  21. Horowitz M, Edelbroek M, Fraser R, et al. Disordered gastric motor function in diabetes mellitus. Recent insights into prevalence, pathophysiology, clinical relevance, and treatment. Scand J Gastroenterol 1991; 26:673.
  22. Mearin F, Malagelada JR. Gastroparesis and dyspepsia in patients with diabetes mellitus. Eur J Gastroenterol Hepatol 1995; 7:717.
  23. Buysschaert M, Moulart M, Urbain JL, et al. Impaired gastric emptying in diabetic patients with cardiac autonomic neuropathy. Diabetes Care 1987; 10:448.
  24. Wegener M, Börsch G, Schaffstein J, et al. Gastrointestinal transit disorders in patients with insulin-treated diabetes mellitus. Dig Dis 1990; 8:23.
  25. Rathmann W, Enck P, Frieling T, Gries FA. Visceral afferent neuropathy in diabetic gastroparesis. Diabetes Care 1991; 14:1086.
  26. Barnett JL, Owyang C. Serum glucose concentration as a modulator of interdigestive gastric motility. Gastroenterology 1988; 94:739.
  27. Schvarcz E, Palmér M, Aman J, et al. Physiological hyperglycemia slows gastric emptying in normal subjects and patients with insulin-dependent diabetes mellitus. Gastroenterology 1997; 113:60.
  28. Jebbink HJ, Bruijs PP, Bravenboer B, et al. Gastric myoelectrical activity in patients with type I diabetes mellitus and autonomic neuropathy. Dig Dis Sci 1994; 39:2376.
  29. Jebbink RJ, Samsom M, Bruijs PP, et al. Hyperglycemia induces abnormalities of gastric myoelectrical activity in patients with type I diabetes mellitus. Gastroenterology 1994; 107:1390.
  30. Rayner CK, Horowitz M. Gastrointestinal motility and glycemic control in diabetes: the chicken and the egg revisited? J Clin Invest 2006; 116:299.
  31. Fraser RJ, Horowitz M, Maddox AF, et al. Hyperglycaemia slows gastric emptying in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1990; 33:675.
  32. Fraser R, Horowitz M, Dent J. Hyperglycaemia stimulates pyloric motility in normal subjects. Gut 1991; 32:475.
  33. 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.
  34. Horowitz M, Harding PE, Maddox AF, et al. Gastric and oesophageal emptying in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1989; 32:151.
  35. Horowitz M, Maddox AF, Wishart JM, et al. Relationships between oesophageal transit and solid and liquid gastric emptying in diabetes mellitus. Eur J Nucl Med 1991; 18:229.
  36. Chang J, Russo A, Bound M, et al. A 25-year longitudinal evaluation of gastric emptying in diabetes. Diabetes Care 2012; 35:2594.
  37. Bharucha AE, Batey-Schaefer B, Cleary PA, et al. Delayed Gastric Emptying Is Associated With Early and Long-term Hyperglycemia in Type 1 Diabetes Mellitus. Gastroenterology 2015; 149:330.
  38. Groop LC, Luzi L, DeFronzo RA, Melander A. Hyperglycaemia and absorption of sulphonylurea drugs. Lancet 1989; 2:129.
  39. Kong MF, Horowitz M, Jones KL, et al. Natural history of diabetic gastroparesis. Diabetes Care 1999; 22:503.
  40. Jones KL, Russo A, Berry MK, et al. A longitudinal study of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus. Am J Med 2002; 113:449.
  41. von der Ohe MR. Diarrhoea in patients with diabetes mellitus. Eur J Gastroenterol Hepatol 1995; 7:730.
  42. 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.
  43. Duchen LW, Anjorin A, Watkins PJ, Mackay JD. Pathology of autonomic neuropathy in diabetes mellitus. Ann Intern Med 1980; 92:301.
  44. Low PA, Walsh JC, Huang CY, McLeod JG. The sympathetic nervous system in alcoholic neuropathy. A clinical and pathological study. Brain 1975; 98:357.
  45. Wald A. Incontinence and anorectal dysfunction in patients with diabetes mellitus. Eur J Gastroenterol Hepatol 1995; 7:737.
  46. Bytzer P, Talley NJ, Jones MP, Horowitz M. Oral hypoglycaemic drugs and gastrointestinal symptoms in diabetes mellitus. Aliment Pharmacol Ther 2001; 15:137.
  47. Badiga MS, Jain NK, Casanova C, Pitchumoni CS. Diarrhea in diabetics: the role of sorbitol. J Am Coll Nutr 1990; 9:578.
  48. el Newihi H, Dooley CP, Saad C, et al. Impaired exocrine pancreatic function in diabetics with diarrhea and peripheral neuropathy. Dig Dis Sci 1988; 33:705.
  49. Shanahan F, McKenna R, McCarthy CF, Drury MI. Coeliac disease and diabetes mellitus: a study of 24 patients with HLA typing. Q J Med 1982; 51:329.
  50. Cudworth AG, Woodrow JC. Genetic susceptibility in diabetes mellitus: analysis of the HLA association. Br Med J 1976; 2:846.
  51. 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.
  52. Frieling T. [Diagnostic in anorectal disorders]. Praxis (Bern 1994) 2007; 96:243.
  53. Wald A, Tunuguntla AK. Anorectal sensorimotor dysfunction in fecal incontinence and diabetes mellitus. Modification with biofeedback therapy. N Engl J Med 1984; 310:1282.
  54. Schiller LR, Santa Ana CA, Morawski SG, Fordtran JS. Studies of the antidiarrheal action of clonidine. Effects on motility and intestinal absorption. Gastroenterology 1985; 89:982.
  55. Fedorak RN, Field M, Chang EB. Treatment of diabetic diarrhea with clonidine. Ann Intern Med 1985; 102:197.
  56. Soudah HC, Hasler WL, Owyang C. Effect of octreotide on intestinal motility and bacterial overgrowth in scleroderma. N Engl J Med 1991; 325:1461.
  57. Dudl RJ, Anderson DS, Forsythe AB, et al. Treatment of diabetic diarrhea and orthostatic hypotension with somatostatin analogue SMS 201-995. Am J Med 1987; 83:584.
  58. Mourad FH, Gorard D, Thillainayagam AV, et al. Effective treatment of diabetic diarrhoea with somatostatin analogue, octreotide. Gut 1992; 33:1578.
  59. Walker JJ, Kaplan DS. Efficacy of the somatostatin analog octreotide in the treatment of two patients with refractory diabetic diarrhea. Am J Gastroenterol 1993; 88:765.