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Gastrointestinal Manifestations of Diabetes

  • Donald P. Kotler
  • Zheng Lin
  • Il J. Paik
  • Stanley Hsu
Reference work entry

Abstract

Gastrointestinal disorders are common in diabetic patients. While diabetic patients often suffer from the same gastrointestinal disorders as nondiabetic individuals, some conditions are more commonly seen in patients with diabetes. Enteric autonomic neuropathy is believed to be a major contributor to gastrointestinal symptoms as it may affect epithelial cells, muscles, or nerves. Damage and dysfunction may be acute and reversible or chronic and irreversible. There have been advances in the understanding and management of several conditions particularly prevalent in diabetic patients, such as esophageal dysmotility, gastroparesis, and constipation, due mainly to the development of improved techniques to assess and modulate neuromuscular function. Optimal management of a patient with diabetes mellitus includes preventing and treating a wide variety of gastrointestinal complaints beyond the management of glycemia.

Keywords

Motility disorders Gastroesophageal reflux Gastroparesis Intestinal disorders Diarrhea Constipation Incontinence 

References

  1. 1.
    Folwaczny C, Riepl R, Tschöp M, Landgraf R. Gastrointestinal involvement in patients with diabetes mellitus: part I (first of two parts). Epidemiology, pathophysiology, clinical findings. Z Gastroenterol. 1999;37:803–15.PubMedGoogle Scholar
  2. 2.
    Chen P, Zhao J, Gregersen H. Up-regulated expression of advanced glycation end-products and their receptor in the small intestine and colon of diabetic rats. Dig Dis Sci. 2012;57:48–57.CrossRefPubMedGoogle Scholar
  3. 3.
    Nowak TV, Harrington B, Weisbruch JP, Kalbfleisch JH. Structural and functional characteristics of muscle from diabetic rodent small intestine. Am J Physiol. 1990;258:G690–8.PubMedGoogle Scholar
  4. 4.
    Ulrich P, Cerami A. Protein glycation, diabetes, and aging. Recent Prog Horm Res. 2001;56:1–21.CrossRefPubMedGoogle Scholar
  5. 5.
    Sánchez SS, Genta SB, Aybar MJ, Honoré SM, Villecco EI, Sánchez Riera AN. Changes in the expression of small intestine extracellular matrix proteins in streptozotocin-induced diabetic rats. Cell Biol Int. 2000;24:881–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Zoubi SA, Mayhew TM, Sparrow RA. The small intestine in experimental diabetes: cellular adaptation in crypts and villi at different longitudinal sites. Virchows Arch. 1995;426:501–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Zoubi SA, Williams MD, Mayhew TM, Sparrow RA. Number and ultrastructure of epithelial cells in crypts and villi along the streptozotocin-diabetic small intestine: a quantitative study on the effects of insulin and aldose reductase inhibition. Virchows Arch. 1995;427:187–93.CrossRefPubMedGoogle Scholar
  8. 8.
    Talley NJ, Bytzer P, Hammer J, et al. Psychological distress is linked to gastrointestinal symptoms in diabetes mellitus. Am J Gastroenterol. 2001;96:1033–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Frokjaer JB, Andersen SD, Ejskjaer N, Funch-Jensen P, Drewes AM, Gregersen H. Impaired contractility and re-modeling of the upper gastrointestinal tract in diabetes mellitus type-1. World J Gastroenterol. 2007;13:4881–90.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Darwazeh AM, MacFarlane TW, McCuish A, et al. Mixed salivary glucose levels and candidal carriage in patients with diabetes mellitus. J Oral Pathol Med. 1991;20(6):280–3.CrossRefPubMedGoogle Scholar
  11. 11.
    Loo FD, Dodds WJ, Soergel KH, et al. Multipeaked esophageal peristaltic pressure waves in patients with diabetic neuropathy. Gastroenterology. 1985;88:485–91.CrossRefPubMedGoogle Scholar
  12. 12.
    Faraj J, Melander O, Sundkvist G, Olsson R, Thorsson O, Ekberg O, Ohlsson B. Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus. Diabet Med. 2007;24:1235–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Keshavarzian A, Iber FL, Nasrallah S. Radionuclide esophageal emptying and manometric studies in diabetes mellitus. Am J Gastroenterol. 1987;92:625–31.Google Scholar
  14. 14.
    Gustafsson RJ, Littorin B, Berntorp K, Frid A, Thorsson O, Olsson R, et al. Esophageal dysmotility is more common than gastroparesis in diabetes mellitus and is associated with retinopathy. Rev Diabet Stud. 2011;8:268–75.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Rayner CK, Samsom M, Jones KL, et al. Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care. 2001;224:371–81.CrossRefGoogle Scholar
  16. 16.
    Horowitz M, Edelbroek M, Fraser R, Maddox A, Wishart J. Disordered gastric motor function in diabetes mellitus: recent insights into prevalence, pathophysiology, clinical relevance, and treatment. Scand J Gastroenterol. 1991;26:673–84.CrossRefPubMedGoogle Scholar
  17. 17.
    Choung RS, Locker GR, et al. Risk of gastroparesis in subjects with type 1 and 2 diabetes in the general population. Am J Gastroenterol. 2012;107:34–42.CrossRefGoogle Scholar
  18. 18.
    Rey E, Choung RS, Schleck CD, et al. Prevalence of hidden gastroparesis in the community: the gastroparesis “iceberg’. J Neurogastroenterol Motil. 2012;18:34–42.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Parkman HP, Yates K, Hasler WL, et al. Clinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying and gastroparesis severity. Gastroenterology. 2011;140:101–15.CrossRefPubMedGoogle Scholar
  20. 20.
    Hasler WL, Wilson L, Parkman HP, et al. Importance of abdominal pain as a symptom in gastroparesis: relation to clinical factors, disease severity, quality of life, gastric retention, and medication use. Gastroenterology. 2010;138 Suppl 1:S461.Google Scholar
  21. 21.
    Cherian D, Parkman HP. Nausea and vomiting in diabetic and idiopathic gastroparesis. Neurogastroenterol Motil. 2012;24:217. e103.CrossRefPubMedGoogle Scholar
  22. 22.
    Koch KL. Dyspepsia of unknown origin: pathophysiology, diagnosis and treatment. Dig Dis. 1997;15:316–29.CrossRefPubMedGoogle Scholar
  23. 23.
    Mearin F, Camilleri M, Malagelada J-R. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology. 1986;90:1919–25.CrossRefPubMedGoogle Scholar
  24. 24.
    Khoo J, Rayner CK, Jones KL, et al. Pathophysiology and management of gastroparesis. Expert Rev Gastroenterol Hepatol. 2009;3:167–81.CrossRefPubMedGoogle Scholar
  25. 25.
    Grover M, Bernard CE, Pasricha PJ, et al. Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research consortium. Neurogastroenterol Motil. 2012;24:531–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Abell TL, Camilleri M, Donohoe K, et al. Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear medicine. Am J Gastroenterol. 2008;103:753–63.CrossRefPubMedGoogle Scholar
  27. 27.
    Pathikonda M, Sachdeva P, Malhorta N, Fisher RS, Maeurer AH, Parkmean HP. Gastric emptying scintigraphy: is four hours necessary? J Clin Gastroenterol. 2012;46:209–15.CrossRefPubMedGoogle Scholar
  28. 28.
    Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2008;103:18–37.Google Scholar
  29. 29.
    Richard JS, William LW. A technical review and clinical assessment of the wireless motility capsule. Gastroenterol Hepatol. 2011;7:795–804.Google Scholar
  30. 30.
    Kuo B, McCallum RW, Koch KL, et al. Comparison of gastric emptying of a nondigestible capsule to a radiolabelled meal in healthy and gastroparetic subjects. Aliment Pharmacol Ther. 2008;27:186–96.CrossRefPubMedGoogle Scholar
  31. 31.
    Wang Q, Ito M, Adams K, et al. Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome. Am J Med Genet A. 2004;131:50–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Simonetto DA, Oxentenko AS, Herman ML, Szostek JH. Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin Proc. 2012;87:114–19.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Cervera A, Wajcberg E, Sriwijitkamol A, Fernandez M, Zuo P, Triplitt C, et al. Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes. Am J Physiol Endocrinol Metab. 2008;294:E846–52.CrossRefPubMedGoogle Scholar
  34. 34.
    Vella A, Bock G, Giesler PD, et al. Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. Diabetes. 2007;56:1475–80.CrossRefPubMedGoogle Scholar
  35. 35.
    FDA requires boxed warning and risk mitigation strategy for metoclopramide-containing drugs. FDA 26 February 2009. Available at: http://www.fda.gov/newevents/newsroom/pressan-nouncements/ucm149533.htm.
  36. 36.
    Rossi M, Giorgi G. Domperidone and long QT syndromes. Curr Drug Saf. 2010;5:257–62.CrossRefPubMedGoogle Scholar
  37. 37.
    Asakawa A, Ueno N, Katagi M, Ijuin Y, Morita Y, Mizuno S, Inui T, Sakamaki R, Shinfuku N, Uemoto M. Mosapride improves food intake, while not worsening glycemic control and obesity, in ob/ob obese mice with decreased gastric emptying. J Diabetes Complications. 2006;20:56–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Kawamura E, Enomoto M, Kotani K, Hagihara A, Fujii H, Kobayashi S, Iwai S, Morikawa H, Kawabe J, Tominaga K, Tamori A, Shiomi S, Kawada N. Effect of mosapride citrate on gastric emptying in interferon-induced gastroparesis. Dig Dis Sci. 2012;57:1510–6.CrossRefPubMedGoogle Scholar
  39. 39.
    Barrett TW, DiPersio DM, Jenkins CA, et al. A randomized, placebo-controlled trial of ondansetron, metoclopramide, and promethazine in adults. Am J Emerg Med. 2011;29:247–55.CrossRefPubMedGoogle Scholar
  40. 40.
    Chong K, Dhatariya K. A case of severe, refractory diabetic gastroparesis managed by prolonged use of aprepitant. Nat Rev Endocrinol. 2009;5:285–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Allen JH, de Moore GM, Heddle R, et al. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut. 2004;53:1566–70.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Prakash C, Lustman PJ, Freedland KE, et al. Tricyclic antidepressants for functional nausea and vomiting: clinical outcome in 37 patients. Dig Dis Sci. 1998;43:1951–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Sawhney MS, Prakash C, Lustman PJ, et al. Tricyclic antidepressants for chronic vomiting in diabetic patients. Dig Dis Sci. 2007;52:418–24.CrossRefPubMedGoogle Scholar
  44. 44.
    Lustman PJ, Griffith LS, Clouse RE, et al. Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial. Psychosom Med. 1997;59:241–50.CrossRefPubMedGoogle Scholar
  45. 45.
    Kim SW, Shin IS, Kim JM, et al. Mirtazapine for severe gastroparesis unresponsive to conventional prokinetic treatment. Psychosomatics. 2006;47:440–2.CrossRefPubMedGoogle Scholar
  46. 46.
    Sarosiek I, Davis B, Eichler E, McCallum RW. Surgical approaches to treatment of gastroparesis: gastric electrical stimulation, pyloroplasty, total gastrectomy and enteral feeding tubes. Gastroenterol Clin North Am. 2015;44:151–67.CrossRefPubMedGoogle Scholar
  47. 47.
    Hirata A, Kishida K, Nakatsuji H, Inoue K, Hiuge-Shimizu A, Funahashi T, Shimomura I. High prevalence of gastroesophageal reflux symptoms in type 2 diabetics with hypoadiponectinemia and metabolic syndrome. Nutr Metab (Lond). 2012;9:4.CrossRefGoogle Scholar
  48. 48.
    Sharma P, McQuaid KR, Dent J, et al. A critical review of the diagnosis and management of Barrett’s esophagus: the AGA Chicago workshop. Gastroenterology. 2004;127:310–30.CrossRefPubMedGoogle Scholar
  49. 49.
    Labenz J, Malfertheiner P. Treatment of uncomplicated reflux disease. World J Gastroenterol. 2005;11:4291–9.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Wilson JA, Vela MF. New esophageal function testing (impedance, Bravo pH monitoring, and high-resolution manometry): clinical relevance. Curr Gastroenterol Rep. 2008;10:222–30.CrossRefPubMedGoogle Scholar
  51. 51.
    del Genio G, Tolone S, del Genio F, et al. Prospective assessment of patient selection for antireflux surgery by combined multichannel intraluminal impedance pH monitoring. J Gastrointest Surg. 2008;12:1491–6.CrossRefPubMedGoogle Scholar
  52. 52.
    Everhart J, Wright D. Diabetes mellitus as a risk factor for pancreatic cancer a meta-analysis. J Am Med Assoc. 1995;273:1605–9.CrossRefGoogle Scholar
  53. 53.
    Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A, et al. Type-II diabetes and pancreatic cancer a meta-analysis of 36 studies. Br J Cancer. 2005;92:2076–83.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Fisher WE, Boros LG, Schirmer WJ. Insulin promotes pancreatic cancer evidence for endocrine influence on exocrine pancreatic tumors. J Surg Res. 1996;63:310–3.CrossRefPubMedGoogle Scholar
  55. 55.
    Schneider MB, Matsuzaki H, Haorah J, et al. Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology. 2001;120:1263–70.CrossRefPubMedGoogle Scholar
  56. 56.
    Bell ET. Carcinoma of the pancreas. I. A. clinical and pathological study of 609 necropsied cases II. The relation of carcinoma of the pancreas to diabetes. Am J Pathol. 1957;33:499.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Stone BG, Gavaler JS, Belle SH, et al. Impairment of gallbladder emptying in diabetes mellitus. Gastroenterology. 1988;95:170–6.CrossRefPubMedGoogle Scholar
  58. 58.
    Upp JR, Nealon WH, Singh P, et al. Correlation of cholecystokinin receptors with gallbladder contractility in patients with gallstones. Ann Surg. 1987;205:641–8.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Keshavarzian A, Iber FL. Intestinal transit in insulin-requiring diabetics. Am J Gastroenterol. 1986;81:257–60.PubMedGoogle Scholar
  60. 60.
    Cuzick J, Babiker AG. Pancreatic cancer, alcohol, diabetes mellitus, and gallbladder disease. Int J Cancer. 1989;43:415–21.CrossRefPubMedGoogle Scholar
  61. 61.
    Saslow SB, Camilleri M. Diabetic diarrhea. Semin Gastrointest Dis. 1995;6:187.PubMedGoogle Scholar
  62. 62.
    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.CrossRefPubMedGoogle Scholar
  63. 63.
    Fedorak RN, Field M, Chang EB. Treatment of diabetic diarrhea with clonidine. Ann Intern Med. 1985;102:197–9.CrossRefPubMedGoogle Scholar
  64. 64.
    Von der Ohe MR, Camilleri M, Thomforde GM, et al. Differential regional effects of octreotide on human gastrointestinal motor function. Gut. 1995;36:743–8.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Lee TH, Lee JS. Ramosetron might be useful for treating diabetic diarrhea with a rapid small bowel transit time. Korean J Intern Med. 2013;28:106–7.CrossRefPubMedGoogle Scholar
  66. 66.
    Krishnan B, Babu S, Walker J, Walker AB, Pappachan JM. Gastrointestinal complications of diabetes mellitus. World J Diabetes. 2013;4:51–63.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Battle WM, Snape WR, Alavi A, et al. Colonic dysfunction in diabetes mellitus. Gastroenterology. 1980;79:1217–21.PubMedGoogle Scholar
  68. 68.
    Lysy J, Karmeli F, Sestieri M, et al. Decreased substance P content in the rectal mucosa of diabetics with diarrhea and constipation. Metabolism. 1997;46:730–34.CrossRefPubMedGoogle Scholar
  69. 69.
    Russo A, Botten R, Kong MF, Chapman IM, Fraser RJ, Horowitz M, Sun WM. Effects of acute hyperglycaemia on anorectal motor and sensory function in diabetes mellitus. Diabet Med. 2004;21:176–82.CrossRefPubMedGoogle Scholar
  70. 70.
    Whitehead WE, Rao SS, Lowry A, Nagle D, Varma M, Bitar KN, Bharucha AE, Hamilton FA. Treatment of fecal incontinence: state of the science summary for the National Institute of Diabetes and Digestive and Kidney Diseases workshop. Am J Gastroenterol. 2015;110:138–46.CrossRefPubMedGoogle Scholar
  71. 71.
    Wald A, Tunuguntla K. Anorectal sensorimotor dysfunction, fecal incontinence and diabetes mellitus. N Engl J Med. 1984;310:1282–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Carrington EV, Evers J, Grossi U, Dinning PG, Scott SM, O'Connell PR, et al. A systematic review of sacral nerve stimulation mechanisms in the treatment of fecal incontinence and constipation. Neurogastroenterol Motil. 2014;26:1222–37.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Donald P. Kotler
    • 1
  • Zheng Lin
    • 2
  • Il J. Paik
    • 3
  • Stanley Hsu
    • 4
  1. 1.Division of Gastroenterology and Liver DiseasesMount Sinai St. Luke’s and Mount Sinai West Hospitals, Icahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.EastonUSA
  3. 3.Division of Gastroenterology and Liver DiseasesMount Sinai St. Luke’s and Mount Sinai West HospitalsNew YorkUSA
  4. 4.GastroenterologyPrinceton HealthCare SystemPrincetonUSA

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