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Current Treatment Options in Gastroenterology

, Volume 15, Issue 4, pp 460–474 | Cite as

Diabetes Mellitus and the Colon

  • Marc S. Piper
  • Richard J. SaadEmail author
Motility (H Parkman and R Schey, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Motility

Opinion statement

Diabetes mellitus (DM) can affect the structure and function of the colon promoting commonly encountered lower gastrointestinal symptoms such as constipation, diarrhea, abdominal distention, bloating, and abdominal pain. Specific colonic disorders for which adults with DM are at greater risk include chronic constipation, enteropathic diarrhea, colorectal cancer (CRC), inflammatory bowel disease, microscopic colitis, and Clostridium difficile colitis. Smooth muscle structure and function, density of the interstitial cells of Cajal, and the health and function of the autonomic and enteric nerves of the colon are all potential affected by DM. These effects can in turn lead to alterations in colon motility, visceral sensation, immune function, endothelial function, and the colonic microbiome. The evaluation and treatment for slow transit constipation as well as pelvic floor dysfunction should be considered when constipation symptoms are refractory to initial treatment measures. DM-related medications and small bowel conditions such as celiac disease and small intestinal bowel overgrowth should be considered and excluded before a diagnosis of enteropathic diarrhea is made. Given the higher risk of CRC, adults with DM should be appropriately screened and may require a longer bowel preparation to ensure an adequate evaluation.

Keywords

Diabetes Colon Slow transit constipation Diarrhea 

Notes

Compliance with ethical standards

Conflict of interest

Marc S. Piper declares that he has no conflict of interest.

Richard J. Saad acts as a consultant for Ironwood, Allergan, and Synergy pharmaceuticals.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as • Of importance •• Of major importance

  1. 1.
    National Center for Chronic Disease Prevention and Health Promotion, Division of Diabetes Translation. In: Diabetes Home. Centers for Disease Control and Prevention. 2017. https://www.cdc.gov/diabetes/data/index.html. Last Updated: 12 Jan 2017.
  2. 2.
    Guariguata L, Whiting DR, Hambleton I, et al. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103(2):137–49.CrossRefPubMedGoogle Scholar
  3. 3.
    Horváth VJ, Putz Z, Izbéki F, et al. Diabetes-related dysfunction of the small intestine and the colon: focus on motility. Curr Diab Rep. 2015;15(11):94.CrossRefPubMedGoogle Scholar
  4. 4.
    Bril F, Cusi K. Nonalcoholic fatty liver disease. Endocrinol Metab Clin N Am. 2016;45(4):765–81.CrossRefGoogle Scholar
  5. 5.
    Akirov A. Co-occurrence of type 1 diabetes mellitus and celiac disease. World J Diabetes. 2015;6(5):707.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Feldman M, Schiller LR. Disorders of gastrointestinal motility associated with diabetes mellitus. Ann Intern Med. 1983;98:378–84.CrossRefPubMedGoogle Scholar
  7. 7.
    Bytzer P, Talley NG, Leemon M, et al. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 1500 adults. Arch Intern Med. 2001;161:1989–96.CrossRefPubMedGoogle Scholar
  8. 8.
    Maisey A. A practical approach to gastrointestinal complications of diabetes. Diab Ther. 2016;7:379–86.CrossRefGoogle Scholar
  9. 9.
    Yarandi SS, Srinivasan S. Diabetic gastrointestinal motility disorders and the role of the enteric nervous system: current status and future directions. Neurogastroenterol Motil. 2014;26(5):611–24.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Domènech A, Pasquinelli G, De Giorgio R, et al. Morphofunctional changes underlying intestinal dysmotility in diabetic RIP-I/hIFNβ transgenic mice. Int J Exp Pathol. 2011;92(6):400–12.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Du F, Wang L, Qian W, et al. Loss of enteric neurons accompanied by decreased expression of GDNF and PI3K/Akt pathway in diabetic rats. Neurogastroenterol Motil. 2009;21(11):1229–e114.CrossRefPubMedGoogle Scholar
  12. 12.
    Furlan MMDP, Molinari SL, Neto M, et al. Morphoquantitative effects of acute diabetes on the myenteric neurons of the proximal colon of adults rats. Arq Neuro Psiquiatr. 2002;60(3):576–81.CrossRefGoogle Scholar
  13. 13.
    Nakahara M, Isozaki K, Hirota S, et al. Deficiency of KIT-positive cells in the colon of patients with diabetes mellitus. J Gastroenterol Hepatol. 2002;17(6):666–70.CrossRefPubMedGoogle Scholar
  14. 14.
    Dong L, Liang X, Sun B, et al. Impairments of the primary afferent nerves in a rat model of diabetic visceral hyposensitivity. Mol Pain. 2015;11:74.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhao M, Liao D, Zhao J. Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes. 2017;8(6):249–69.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Azpiroz F, Malagelada C. Diabetic neuropathy in the gut: pathogenesis and diagnosis. Diabetologia. 2016;59(3):404–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Celik AF, Osar Z, Damci T, et al. How important are the disturbances of lower gastrointestinal bowel habits in diabetic outpatients? Am J Gastroenterol. 2001;96(4):1314–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Enck P, Rathmann W, Spiekermann M, et al. Prevalence of gastrointestinal symptoms in diabetic patients and non-diabetic subjects. Z Gastroenterol. 1994;32:637–41.PubMedGoogle Scholar
  19. 19.
    Maleki D, Locke GR, Camilleri M, et al. Gastrointestinal tract symptoms among persons with diabetes mellitus in the community. Arch Intern Med. 2000;160(18):2808–16.CrossRefPubMedGoogle Scholar
  20. 20.
    Maleki D, Camilleri M, Burton DD, et al. Pilot study of pathophysiology of constipation among community diabetics. Dig Dis Sci. 1998;43(11):2373–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Maxton DG, Whorwell PG. Functional bowel symptoms in diabetes: the role of autonomic neuropathy. Postgrad Med J. 1991;67(793):991–3.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    • Prasad VGM, Abraham P. Management of chronic constipation in patients with diabetes mellitus. Indian J Gastroenterol. 2017;36(1):11–22. A recent and comprehensive review that discusses the treatment of constipation in diabeticsCrossRefPubMedGoogle Scholar
  23. 23.
    Bharucha AE, Pemberton JH, Locke GR III. American Gastroenterological Association technical review on constipation. Gastroenterology. 2013;144(1):218–38.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Rao SSC, Bharucha AE, Chiarioni G, et al. Anorectal disorders. Gastroenterology. 2016;150(6):1430–42.CrossRefGoogle Scholar
  25. 25.
    Rao SSC, Camilleri M, Hasler WL, et al. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterol Motil. 2011;23(1):8–23.CrossRefPubMedGoogle Scholar
  26. 26.
    Panesar PS, Kumari S. Lactulose: production, purification and potential applications. Biotechnol Adv. 2001;29(6):940–8.CrossRefGoogle Scholar
  27. 27.
    Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011;365:527–36.CrossRefPubMedGoogle Scholar
  28. 28.
    Miner PB Jr, Koltun WD, Wiener GJ, et al. A randomized phase III clinical trial of plecanatide, a uroguanylin analog, in patients with chronic idiopathic constipation. Am J Gastroenterol. 2017;112(4):613–21.CrossRefPubMedGoogle Scholar
  29. 29.
    •• Christie J, Shroff S, Shahnavaz N, et al. A randomized, double-blind, placebo-controlled trial to examine the effectiveness of lubiprostone on constipation symptoms and colon transit time in diabetic patients. Am J Gastroenterol. 2017;112(2):356–64. Randomized, controlled trial (lubiprostone versus placebo) which demonstrates the effectiveness of lubiprostone in improving colonic transit time and bowel function in diabetic patients.CrossRefPubMedGoogle Scholar
  30. 30.
    Camilleri M, Kerstens R, Rykx A, et al. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008;358:2344–54.CrossRefPubMedGoogle Scholar
  31. 31.
    •• Bharucha AE, Low P, Camilleri M, et al. A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation. Gut. 2013;62(5):708–15. Randomized, controlled trial (pyridostigmine versus placebo) which shows improvement in colonic transit time and bowel function in diabetic patients (without defecatory disorders) on pyridostigmine.CrossRefPubMedGoogle Scholar
  32. 32.
    Lysy J. The prevalence of chronic diarrhea among diabetic patients. Am J Gastroenterol. 1999;94(8):2165–70.CrossRefPubMedGoogle Scholar
  33. 33.
    Schiller LR, Pardi DS, Sellin JH. Chronic diarrhea: diagnosis and management. Clin Gastroenterol Hepatol. 2017;15(2):182–93.CrossRefPubMedGoogle Scholar
  34. 34.
    Fernández-Bañares F, Esteve M, Viver JM. Fructose-sorbitol malabsorption. Curr Gastroenterol Rep. 2009;11(5):368–74.CrossRefPubMedGoogle Scholar
  35. 35.
    Gould M, SellinJH. Diabetic diarrhea. Curr Gastroenterol Rep. 2009;11(5):354–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Halmos EP, Power VA, Shepherd SJ, et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014;146(1):67–75.CrossRefPubMedGoogle Scholar
  37. 37.
    Hansen M, Sonne DP, Mikkelsen KH, et al. Bile acid sequestrants for glycemic control in patients with type 2 diabetes: a systematic review with meta-analysis of randomized controlled trials. J Diabetes Complicat. 2017;31(5):918–27.CrossRefPubMedGoogle Scholar
  38. 38.
    Brandt LJ, Chey WD, Foxx-Orenstein AE, et al. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2008;104:S1–S35.CrossRefGoogle Scholar
  39. 39.
    Fedorak RN. Treatment of diabetic diarrhea with clonidine. Ann Intern Med. 1985;102(2):197–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Fragkos KC, Zárate-Lopez N, Frangos CC. What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans. Ther Adv Gastroenterol. 2016;9(3):282–301.CrossRefGoogle Scholar
  41. 41.
    Bretzke G. Therapy of diarrhea in diabetic enteropathy with clonidine. Z Gesante Inn Med. 1987;42:680–2.Google Scholar
  42. 42.
    Morali GA, Braverman DZ, Lissi J, et al. Effect of clonidine on gallbladder contraction and small bowel transit time in insulin-treated diabetics. Am J Gastroenterol. 1991;86(8):995–9.PubMedGoogle Scholar
  43. 43.
    Mourad FH, Gorard D, Thillainayagam AV, et al. Effective treatment of diabetic diarrhoea with somatostatin analogue, octreotide. Gut. 1992;33(11):1578–80.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Nakabayashi H. Marked improvement of diabetic diarrhea with the somatostatin analogue octreotide. Arch Intern Med. 1994;154(16):1863–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Tsai ST. Diabetic diarrhea and somatostatin. Ann Intern Med. 1986;104(6):894.CrossRefPubMedGoogle Scholar
  46. 46.
    Murao S, Hosokawa H. Serotonin 5-HT3 receptor antagonist for treatment of severe diabetic diarrhea. Diabetes Care. 2010;33(3):e38.CrossRefPubMedGoogle Scholar
  47. 47.
    Bossi A, Baresi A, Ballini A, et al. Ondasentron in the treatment of diabetic diarrhea. Diabetes Care. 1994;17(5):453–4.CrossRefPubMedGoogle Scholar
  48. 48.
    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(1):106–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Garsed K, Chernova J, Hastings M, et al. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut. 2014;63(10):1617–25.CrossRefPubMedGoogle Scholar
  50. 50.
    Barone BB, Yeh HC, Snyder CF, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA. 2008;300(23):2754–64.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    de Kort S, Masclee AA, Sanduleanu S, et al. Higher risk of colorectal cancer in patients with newly diagnosed diabetes mellitus before the age of colorectal cancer screening initiation. Sci Rep. 2017;7:46527.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Giovannucci E. Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr. 2007;86(3):836S–42S.Google Scholar
  53. 53.
    González N, Prieto I, del Puerto-Nevado L, et al. 2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications. Oncotarget. 2017;8(11):18456–85.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Tsilidis KK, Kasimis JC, Lopez DS, et al. Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ. 2015;350:g7607.CrossRefPubMedGoogle Scholar
  55. 55.
    Giovannuci E, Harlan DM, Arhcer MC, et al. Diabetes and cancer. A consensus report. CA Cancer J Clin. 2010;60(4):207–21.CrossRefGoogle Scholar
  56. 56.
    Giovannucci E. Insulin and colon cancer. Cancer Causes Control. 1995;6(2):164–79.CrossRefPubMedGoogle Scholar
  57. 57.
    Reinmuth N, Liu W, Fan F, et al. Blockade of insulin-like growth factor I receptor function inhibits growth and angiogensis of colon cancer. Clin Canc Res. 2002;8(10):3259–69.Google Scholar
  58. 58.
    Meyerhardt JA, Catalano PJ, Haller DG, et al. Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol. 2016;21(3):433–40.CrossRefGoogle Scholar
  59. 59.
    Stein KB, Snyder CF, Barone BB, et al. Colorectal cancer outcomes, recurrence, and complications in persons with and without diabetes mellitus: a systematic review and meta-analysis. Dig Dis Sci. 2010;55(7):1839–51.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Fransgaard T, Thygesen LC, Gögenur I. Metformin increases overall survival in patients with diabetes undergoing surgery for colorectal cancer. Ann Surg Oncol. 2016;23(5):1569–75.CrossRefPubMedGoogle Scholar
  61. 61.
    Paulson EC, Thompson E, Mahmoud N. Surgical site infection and colorectal surgical procedures: a prospective analysis of risk factors. Surg Infect. 2017;18(4):520–6.CrossRefGoogle Scholar
  62. 62.
    Franciosi M, Lucisano G, Lapice E, et al. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS One. 2013;8(8):e71583.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Landman GWD, van Hateren KN, et al. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care. 2010;33(2):322–6.CrossRefPubMedGoogle Scholar
  64. 64.
    Wu L, Zhu J, Prokop LG, et al. Pharmacologic therapy of diabetes and overall cancer risk and mortality: a meta-analysis of 265 studies. Sci Rep. 2015;5(1):C15.Google Scholar
  65. 65.
    Higurashi T, Hosono K, Takahashi H, et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 2016;17(4):475–83.CrossRefPubMedGoogle Scholar
  66. 66.
    Dik VK, LMG M, Hyk M, et al. Predicting inadequate bowel preparation for colonoscopy in participants receiving split-dose bowel preparation: development and validation of a prediction score. Gastrointest Endosc. 2015;81(3):665–72.CrossRefPubMedGoogle Scholar
  67. 67.
    Mandolesi D, Frazzoni L, Bazzoli F, et al. The management of “hard-to-prepare” colonoscopy patients. Expert Rev Gastroenterol Hepatol. 2017;93(816):1–10.Google Scholar
  68. 68.
    Ozturk NA, Gokturk HS, Demir M, et al. The effect of autonomous neuropathy on bowel preparation in type 2 diabetes mellitus. Int J Color Dis. 2009;24(12):1407–12.CrossRefGoogle Scholar
  69. 69.
    Porter NR, Eberth JM, Samson ME, et al. Peer reviewed: diabetes status and being up-to-date on colorectal cancer screening, 2012 behavioral risk factor surveillance system. Prev Chronic Dis. 2016;13:150391.CrossRefGoogle Scholar
  70. 70.
    Hayes A, Buffum M, Hughes J. Diabetic colon preparation comparison study. Gastroenterol Nurs. 2001;34(5):377–82.CrossRefGoogle Scholar
  71. 71.
    Kim YH, Seo EH, Lee JS, et al. Inadequate bowel cleansing efficacy of split-dose polyethylene glycol for colonoscopy in type 2 diabetic patients: a prospective and blinded study. J Clin Gastroenterol. 2017;51(3):240–6.PubMedGoogle Scholar
  72. 72.
    Alvarez-Gonzalez MA, Flores-Le Roux JA. Bowel preparation for colonoscopy in diabetic patients. Dis Colon Rectum. 2017;49(2):203–4.Google Scholar
  73. 73.
    Panarese A. Bowel preparation in diabetic patients undergoing colonoscopy. Dis Colon Rectum. 2017;49(2):202.Google Scholar
  74. 74.
    Pardi DS. Diagnosis and management of microscopic colitis. Am J Gastroenterol. 2016;112(1):78–85.CrossRefPubMedGoogle Scholar
  75. 75.
    Pardi DS, Tremaine WJ, Carrasco-Labra A. American Gastroenterological Association institute technical review on the medical management of microscopic colitis. Gastroenterology. 2016;150(1):247–74.CrossRefPubMedGoogle Scholar
  76. 76.
    Vigren L, Tysk C, Ström M, et al. Celiac disease and other autoimmune diseases in patients with collagenous colitis. Scand J Gastroenterol. 2013;48(8):944–50.CrossRefPubMedGoogle Scholar
  77. 77.
    Fernández-Bañares F, de Sousa MR, Salas A, et al. Epidemiological risk factors in microscopic colitis: a prospective case–control study. Inflamm Bowel Dis. 2013;19(2):411.PubMedGoogle Scholar
  78. 78.
    Nguyen GC, Smalley WE, Vege SS, et al. American Gastroenterological Association Institute guideline on the medical management of microscopic colitis. Gastroenterology. 2016;150(1):242–6.CrossRefPubMedGoogle Scholar
  79. 79.
    Park T. Microscopic colitis: a review of etiology, treatment and refractory disease. World J Gastroenterol. 2015;21(29):8804.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Leeds JS, Hopper AD, Hadjivassiliou M, et al. Inflammatory bowel disease is more common in type 1 diabetes mellitus. Gut. 2011;60(S1):A208.CrossRefGoogle Scholar
  81. 81.
    Maconi G, Furfaro F, Sciurti R, et al. Glucose intolerance and diabetes mellitus in ulcerative colitis: pathogenetic and therapeutic implications. World J Gastroenterol. 2014;20(13):3507–15.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Sehgal R, Berg A, Figueroa R, et al. Risk factors for surgical site infections after colorectal resection in diabetic patients. J Am Coll Surg. 2011;212(1):29–34.CrossRefPubMedGoogle Scholar
  83. 83.
    Teslova T, Kim M, Lukin D. Diabetes is associated with worse outcomes in inflammatory bowel disease. Inflamm Bowel Dis. 2017;23:S19.Google Scholar
  84. 84.
    Coakley BA, Divino CM. Identifying factors predictive of surgical-site infections after colectomy for fulminant ulcerative colitis. Am Surg. 2012;78(4):481–4.PubMedGoogle Scholar
  85. 85.
    Eliakim-Raz N, Fishman G, Yahav D, et al. Predicting Clostridium difficile infection in diabetic patients and the effect of metformin therapy: a retrospective, case–control study. Eur J Clin Microbiol Infect Dis. 2015;34(6):1201–5.CrossRefPubMedGoogle Scholar
  86. 86.
    Luca MC, Rosu F, Hurmuzache M, et al. Updates in the assessment of risk factors in clostridium difficile infection in patients with infectious diseases. Farmacia. 2016;64(1):112–5.Google Scholar
  87. 87.
    Shakov R, Salazar RS, Kagunye SK, et al. Diabetes mellitus as a risk factor for recurrence of Clostridium difficile infection in the acute care hospital setting. Am J Infect Control. 2011;39(3):194–8.CrossRefPubMedGoogle Scholar
  88. 88.
    Debast SB, Bauer MP, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20(S2):1–26.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Providence-Park HospitalMichigan State University College of Human MedicineLansingUSA
  2. 2.Michigan Medicine at the University of MichiganAnn ArborUSA

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