Diagnostic Approach

  • Alen Bišćanin
Part of the Clinical Gastroenterology book series (CG)


Diabetic autonomic neuropathy and coexisting histomorphological and biomechanical gastrointestinal tract remodeling lead to impaired gut motility and bacterial overgrowth in diabetics. The whole gastrointestinal tract may be affected, and we can expect motility disorder, abnormal secretion, absorption and transportation. Clinical consequences of colon engagement are diarrhea, constipation, and fecal incontinence (and their alternation or combination) as the most frequent symptoms of enteropathy. In general, diagnosis of diabetic autonomic neuropathy-related diarrhea, constipation, or fecal incontinence will be made by exclusion. There are no strict recommendations about diagnostic workout, and the most usual recommendations for the diagnostic approach to diabetic autonomic neuropathy-related gastrointestinal disorders are based on the experience of individual clinical centers. Diagnostic workout always starts with a detailed patient history, physical examination, and pathological findings, which indicate further specific testing.


Diabetic autonomic neuropathy Gastrointestinal complications of diabetes mellitus Diabetic diarrhea Constipation Fecal incontinence Small-intestine bacterial overgrowth (SIBO) 


  1. 1.
    Drewes AM, Søfteland E, Dimcevski G, Farmer AD, Brock C, Frøkjær JB, et al. Brain changes in diabetes mellitus patients with gastrointestinal symptoms. World J Diabetes. 2016;7:14–26.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    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
  3. 3.
    Sims MA, Hasler WL, Chey WD, Kim MS, Owyang C. Hyperglycemia inhibits mechanoreceptor-mediated gastrocolonic responses and colonic peristaltic reflexes in healthy humans. Gastroenterology. 1995;108:350–9.CrossRefGoogle Scholar
  4. 4.
    Drossman DA, Hasler WL. Rome IV—functional GI disorders: disorders of gut–brain interaction. Gastroenterology. 2016;150(6):1257–61.CrossRefPubMedGoogle Scholar
  5. 5.
    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
  6. 6.
    Eherer AJ, Fordtran JS. Fecal osmotic gap and pH in experimental diarrhea of various causes. Gastroenterology. 1992;103(2):545–51.CrossRefPubMedGoogle Scholar
  7. 7.
    Sweetser S. Evaluating the patient with diarrhea: a case-based approach. Mayo Clin Proc. 2012;87(6):596–602.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Schiller RL, Sellin HJ. Diarrhea. In: Lawrence RS, Sleisenger MH, Feldman M, editors. Sleisenger and Fordtran’s gastrointestinal and liver disease: pathophysiology, diagnosis, management. Philadelphia: Saunders/Elsevier; 2010. p. 211–32.Google Scholar
  9. 9.
    Donowitz M, Kokke FT, Saidi R. Evaluation of patients with chronic diarrhea. N Engl J Med. 1995;332(11):725–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Fine KD, Ogunji F. A new method of quantitative fecal fat microscopy and its correlation with chemically measured fecal fat output. Am J Clin Pathol. 2000;113(4):528–34.CrossRefPubMedGoogle Scholar
  11. 11.
    Gould M, Sellin JH. Diabetic diarrhea. Curr Gastroenterol Rep. 2009;11:354.CrossRefGoogle Scholar
  12. 12.
    Vanner S. The lactulose breath test for diagnosing SIBO in IBS patients: another nail in the coffin. Am J Gastroenterol. 2008;103:96465.CrossRefGoogle Scholar
  13. 13.
    Lysy J, Israeli E, Goldin E. The prevalence of chronic diarrhea among diabetic patients. Am J Gastroenterol. 1999;94:2165–70.CrossRefGoogle Scholar
  14. 14.
    Berchtold P, Dahlqvist A, Gustafson A, Asp NG. Effects of a biguanide (metformin) on vitamin B12 and folic acid absorption and intestinal enzyme activities. Scand J Gastroenterol. 1971;6:751–4.CrossRefPubMedGoogle Scholar
  15. 15.
    Ratnaike RN, Jones TE. Mechanisms of drug-induced diarrhoea in the elderly. Drugs Aging. 1998;13:245–53.CrossRefPubMedGoogle Scholar
  16. 16.
    Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth. Gastroenterol Hepatol. 2007;3(2):112–22.Google Scholar
  17. 17.
    Corazza GR, Menozzi MG, Strocchi A, Rasciti L, Vaira D, Lecchini R, et al. The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing. Gastroenterology. 1990;98(2):302–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Ghoshal UC, Ghoshal U, Das K, Misra A. Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome and its relationship with oro-cecal transit time. Indian J Gastroenterol. 2006;25:6–10.PubMedGoogle Scholar
  19. 19.
    Ghoshal UC, Shukla R, Ghoshal U. Small intestinal bacterial overgrowth and irritable bowel syndrome: a bridge between functional organic dichotomy. Gut Liver. 2017;11(2):196–208.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ghoshal UC. How to interpret hydrogen breath tests. J Neurogastroenterol Motility. 2011;17(3):312–7.CrossRefGoogle Scholar
  21. 21.
    Sellin JH, Chang EB. Therapy insight: gastrointestinal complications of diabetes—pathophysiology and management. Nat Clin Pract Gastroenterol Hepatol. 2008;5(3):162–71.CrossRefPubMedGoogle Scholar
  22. 22.
    Rosa-e-Silva L, Troncon LE, Oliveira RB, Foss MC, Braga FJ, Gallo Júnior L, et al. Rapid distal small bowel transit associated with sympathetic denervation in type I diabetes mellitus. Gut. 1996;39:748–56.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Taniguchi T, Okazaki K, Okamoto M, Seko S, Tanaka J, Uchida K, et al. High prevalence of autoantibodies against carbonic anhydrase II and lactoferrin in type 1 diabetes: concept of autoimmune exocrinopathy and endocrinopathy of the pancreas. Pancreas. 2003;27:26–30.CrossRefPubMedGoogle Scholar
  24. 24.
    Schrader H, Menge BA, Schneider S, Belyaev O, Tannapfel A, Uhl W, et al. Reduced pancreatic volume and beta-cell area in patients with chronic pancreatitis. Gastroenterology. 2009;136:513–22.CrossRefPubMedGoogle Scholar
  25. 25.
    Hardt PD, Ewald N, Bröckling K, Tanaka S, Endo T, Kloer HU, et al. Distinct autoantibodies against exocrine pancreatic antigens in European patients with type 1 diabetes mellitus and non-alcoholic chronic pancreatitis. JOP. 2008;9:683–9.PubMedGoogle Scholar
  26. 26.
    Nunes AC, Pontes JM, Rosa A, Gomes L, Carvalheiro M, Freitas D. Screening for pancreatic exocrine insufficiency in patients with diabetes mellitus. Am J Gastroenterol. 2003;98:2672–5.CrossRefPubMedGoogle Scholar
  27. 27.
    K T, Rao P, Attaluri A, Rao SS. Digital rectal examination is a useful tool for identifying patients with dyssynergia. Clin Gastroenterol Hepatol. 2010;8(11):955–60.CrossRefGoogle Scholar
  28. 28.
    Davila RE, Rajan E, Baron TH, et al. Standards of practice committee, American Society for Gastrointestinal Endoscopy ASGE guideline: colorectal cancer screening and surveillance. Gastrointest Endosc. 2006;63(4):546–57.CrossRefPubMedGoogle Scholar
  29. 29.
    Andrews CN, Storr M. The pathophysiology of chronic constipation. Can J Gastroenterol. 2011;25(Suppl B):16B–21B.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Wald A. Etiology and evaluation of chronic constipation in adults. Talley NJ, ed. UpToDate Inc. Accessed May 2016.
  31. 31.
    Eun Ran K, Poong-Lyul R. How to interpret a functional or motility test - colon transit study. J Neurogastroenterol Motil. 2012;18(1):94–9.CrossRefGoogle Scholar
  32. 32.
    Jung HK, Kim DY, Moon IH. Effects of gender and menstrual cycle on colonic transit time in healthy subjects. Korean J Intern Med. 2003;18:181–6.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Stivland T, Camilleri M, Vassallo M, Proano M, Rath D, Brown M, et al. Scintigraphic measurement of regional gut transit in idiopathic constipation. Gastroenterology. 1991;101:107–15.CrossRefPubMedGoogle Scholar
  34. 34.
    Camilleri M. Scintigraphic biomarkers for colonic dysmotility. Clin Pharmacol Ther. 2010;87:748–53.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Maqbool S, Parkman HP, Friedenberg FK. Wireless capsule motility: comparison of the SmartPill GI monitoring system with scintigraphy for measuring whole gut transit. Dig Dis Sci. 2009;54:2167–74.CrossRefPubMedGoogle Scholar
  36. 36.
    Lee YY, Erdogan A, Rao SSC. How to perform and assess colonic manometry and barostat study in chronic constipation. J Neurogastroenterol Motility. 2014;20(4):547–52.CrossRefGoogle Scholar
  37. 37.
    Bampton PA, Dinning PG. High resolution colonic manometry—what have we learnt?—a review of the literature 2012. Curr Gastroenterol Rep. 2013;15:328.CrossRefPubMedGoogle Scholar
  38. 38.
    Dinning PG, Wiklendt L, Gibbins I, Patton V, Bampton P, Lubowski DZ, et al. Low-resolution colonic manometry leads to a gross misinterpretation of the frequency and polarity of propagating sequences: initial results from fiber-optic high-resolution manometry studies. Neurogastroenterol Motil. 2013;25:640–9.Google Scholar
  39. 39.
    Shafik A, El-Sibai O. Role of rectosigmoid junction in fecal continence: an experimental study. Front Biosci. 1999;4:B9–13.CrossRefPubMedGoogle Scholar
  40. 40.
    Robson KM, Lembo AJ. Fecal incontinence in adults: etiology and evaluation. Talley NJ, ed. UpToDate Inc. Accessed 6 Sept 2017.
  41. 41.
    Sagar PM, Pemberton JH. Anorectal and pelvic floor function. Relevance of continence, incontinence, and constipation. Gastroenterol Clin N Am. 1996;25(1):163–82.CrossRefGoogle Scholar
  42. 42.
    Coller JA. Clinical application of anorectal manometry. Gastroenterol Clin N Am. 1987;16(1):17–33.Google Scholar
  43. 43.
    Lee TH, Bharucha AE. How to perform and interpret a high-resolution anorectal manometry test. J Neurogastroenterol Motil. 2016;22(1):46–59.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Kim AY. How to interpret a functional or motility test — defecography. J Neurogastroenterol Motil. 2011;17(4):416–20.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Lee BE, Kim GH. How to perform and interpret balloon expulsion test. J Neurogastroenterol Motil. 2014;20(3):407–9.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Minguez M, Herreros B, Sanchiz V, Hernandez V, Almela P, Añon R, et al. Predictive value of the balloon expulsion test for excluding the diagnosis of pelvic floor dyssynergia in constipation. Gastroenterology. 2004;126(1):57–62.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Alen Bišćanin
    • 1
    • 2
  1. 1.Department of Gastroenterology and HepatologySestre milosrdnice University Hospital CenterZagrebCroatia
  2. 2.School of MedicineUniversity of ZagrebZagrebCroatia

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