Diabetic autonomic neuropathy of the gastrointestinal tract – etiopathogenesis , diagnosis, treatment and complications

Dorota Kuzemko 1  ,  
Ewa Rymarz 1,  
Chair and Department of Internal Diseases, Medical University, Lublin, Poland / Independent Clinical Hospital No. 1, Lublin, Poland
JPCCR 2017;11(1):6–9
Late complications of diabetes mellitus are a serious challenge for physicians treating diabetic patients. Micro- and macro-angiopathic changes are of the most severe sequels. However, it should be remembered that the effects of long-term diabetes are also associated with changes in the peripheral nervous system. One of the complications most troublesome for patients is diabetic autonomic neuropathy of the gastrointestinal (GI) tract.

The review article presents the pathogenesis of diabetic neuropathy of the autonomous gastrointestinal tract, and advances in the diagnosis and treatment of this disease. The study used materials in the database which demonstrate current standards of conduct, based on the principles of EBM. Brief description of the state of knowledge. Diabetic neuropathy is one of the most common complications of diabetes mellitus. According to epidemiologists, it affects 10% to even 100% of patients with long-standing disease. Damage to the nervous fibres mainly results from hyperglycaemia, which leads to the typical symptoms of dysfunction of GI tract segments. The main additional examinations include abdominal ultrasound (US) and abdominal X-ray. In cases with oesophageal disorders accompanied by dysphagia, gastroscopy is found useful for excluding possible neoplastic lesions. The gold standard for evaluation of gastric emptying is radioisotopic scintigraphy, however it is available only in some specialistic departments. Other recommended methods include: manometry, EGG, insulin tests, NMR and expiratory tests. To date, the problem has been managed symptomatically; in special cases, surgical interventions have been required.

At present, a wide array of treatment options is available, including new forms of drugs and less radical surgical procedures carried out in numerous centres worldwide

Dorota Kuzemko   
Chair and Department of Internal Diseases, Medical University, Lublin, Poland / Independent Clinical Hospital No. 1, Lublin, Poland
1. 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.
2. Janatuinen E, Pikkarainen P, Laakso M, Pyörälä K. Gastrointestinal symptoms in middle-aged diabetic patients. Scand J Gastroenterol. 1993; 28:427.
3. Enck P, Rathmann W, Spiekermann M, et al. Prevalence of gastrointestinal symptoms in diabetic patients and non-diabetic subjects. Z Gastroenterol. 1994; 32:637.
4. Maleki D, Locke GR 3rd, Camilleri M, et al. Gastrointestinal tract symptoms among persons with diabetes mellitus in the community. Arch Intern Med. 2000; 160:2808.
5. Quan C, Talley NJ, Cross S, et al. Development and validation of the Diabetes Bowel Symptom Questionnaire. Aliment Pharmacol Ther. 2003; 17:1179.
6. Sieradzki J, Czupryniak L, Małecki M. Diabetes mellitus. In: Witek P, editor. Diabetic autonomic neuropathy. Ed.2. Gdansk; 2016. p. 635,650.
7. Szelachowska M, Szepietowska. Immune disorders in diabetes. Clinical Diabetology. 2004;5(6):355–364.
8. Legaspi R, Narcisio P. Euglycemic Diabetic Ketoacidosis Due to Gastroparesis, A Local Experience. J Ark Med Soc. 2015; 112(5):62–63.
9. Vassallo M, Camilleri M, Caron BL, Low PA. Gastrointestinal motor dysfunction in acquired selective cholinergic dysautonomia associated with infectious mononucleosis. Gastroenterology. 1991; 100:252.
10. Lobrano A, Blanchard K, Abell TL, et al. Postinfectious gastroparesis related to autonomic failure: a case report. Neurogastroenterol Motil. 2006; 18:162.
11. Ordög T, Takayama I, Cheung WK, et al. Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis. Diabetes. 2000; 49:1731.
12. Horváth VJ, Izbéki F, Lengyel C, Kempler P, Várkonyi T. Diabetic gastroparesis: functional/morphologic background, diagnosis, and treatment options. Curr Diab Rep. 2014;14(9):527. doi: 10.1007/s11892–014–0527–8.
13. Gustafsson R, Littorin B, Berntorp K, Frid A, Thorsson O, Olsson R, Ekberg O, Ohlsson B. Esophageal Dysmotility is More Common Than Gastroparesis in Diabetes Mellitus and is Associated With Retinopathy. Rev Diabet Stud. 2011; 8(2): 268–275.
14. Rayner CK, Samsom M, Jones KL, Horowitz M. Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care. 2001; 24:371.
15. Koch KL, Calles-Escandón J. Diabetic gastroparesis. Gastroenterol Clin North Am. 2015;44(1):39–57. doi: 10.1016/j.gtc.2014.11.005.
16. Adar T, Lysy J. Pseudodyslipidemia: are we over-treating dyslipidemia in diabetic patients with undiagnosed gastroparesis?. Endocrine. 2014;45(1):26–27. doi: 10.1007/s12020–013–0064–2. Epub 2013 Oct 3.
17. Vinik AI, Erbes T. Recognizing and treating diabetic autonomic neuropathy. Cleve Clin J Med. 2001;68:928944.
18. Schiller LR, Santa Ana CA, Schmulen AC, et al. Pathogenesis of fecal incontinence in diabetes mellitus: evidence for international sphincter dysfunction. NEJM. 1982;307:16661671.
19. Hasler WL. Gastroparesis: pathogenesis, diagnosis and management. Nat. Rev. Gastroenterol. Hepatol. 2011; 8: 438–453.
20. Olausson EA, Grundin H, Isaksson M, Brock C, Drewes AM, Attvall S, Simrén M. Postprandial Plasma Glucose Response and Gastrointestinal Symptom Severity in Patients With Diabetic Gastroparesis. J Diabetes Sci Technol. 2014;8(4):881–888. doi: 10.1177/1932296814531098. Epub 2014 May 6.
21. Ramzan Z, Duffy F, Gomez J, Fisher RS, Parkman HP. Continuous glucose monitoring in gastroparesis. Dig Dis Sci. 2011;56(9):2646–2655. doi: 10.1007/s10620–011–1810-z. Epub 2011 Jul 7.
22. Phillips LK, Rayner CK, Jones KL, Horowitz M. Measurement of gastric emptying in diabetes. J Diabetes Complications. 2014;28(6):894–903. doi: 10.1016/j.jdiacomp.2014.06.005. Epub 2014 Jun 17.
23. Somasundaram VH, Subramanyam P, Palaniswamy SS. A gluten-free vegan meal for gastric emptying scintigraphy: establishment of reference values and its utilization in the evaluation of diabetic gastroparesis. Clin Nucl Med. 2014;39(11):960–965.doi:10.1097/RLU.0000000000000549.
24. Sieradzki J, Czupryniak L, Małecki M. Diabetes mellitus. In: Witek P, editor. Diabetic autonomic neuropathy. Ed.2. Gdansk; 2016. p. 665.
25. Sieradzki J, Czupryniak L, Małecki M. Diabetes mellitus. In: Witek P, editor. Diabetic autonomic neuropathy. Ed.2. Gdansk; 2016. p. 666.
26. Wytiaz V, Homko C, Duffy F, et al. Foods provoking and alleviating symptoms in gastroparesis: patient experiences. Dig Dis Sci.2015; 60:1052.
27. Homko CJ, Duffy F, Friedenberg FK, et al. Effect of dietary fat and food consistency on gastroparesis symptoms in patients with gastroparesis. Neurogastroenterol Motil. 2015; 27:501.
28. Parkman HP, Yates KP, Hasler WL, et al. Dietary intake and nutritional deficiencies in patients with diabetic or idiopathic gastroparesis. Gastroenterology.2011; 141:486.
29. Olausson EA, Störsrud S, Grundin H, et al. A small particle size diet reduces upper gastrointestinal symptoms in patients with diabetic gastroparesis: a randomized controlled trial. Am J Gastroenterol. 2014; 109:375.
30. Petrakis IE, Kogerakis N, Vrachassotakis N, et al. Hyperglycemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in healthy subjects. Abdom Imaging. 2002; 27:309.
31. Dudekula A, Rahim S, Bielefeldt K.Time trends in gastroparesis treatment. Dig Dis Sci. 2014; 59: 2656. doi:10.1007/s10620–014–3369-y.
32. McCallum RW, Valenzuela G, Polepalle S, Spyker D. Subcutaneous metoclopramide in the treatment of symptomatic gastroparesis: clinical efficacy and pharmacokinetics. J Pharmacol Exp Ther. 1991; 258:136.
33. Parkman HP, Carlson MR, Gonyer D.Metoclopramide nasal spray is effective in symptoms of gastroparesis in diabetics compared to conventional oral tablet. Neurogastroenterol Motil. 2014;26(4):521–528. doi: 10.1111/nmo.12296. Epub 2013 Dec 25.
34. Parkman HP, Carlson MR, Gonyer D.Metoclopramide Nasal Spray Reduces Symptoms of Gastroparesis in Women, but not Men, With Diabetes: Results of a Phase 2B Randomized Study. Clin Gastroenterol Hepatol. 2015;13(7):1256–1263.e1. doi: 10.1016/j.cgh.2014.12.030. Epub 2015 Jan 7.
35. Sugumar A, Singh A, Pasricha PJ. A systematic review of the efficacy of domperidone for the treatment of diabetic gastroparesis. Clin Gastroenterol Hepatol. 2008; 6:726.
36. Sieradzki J, Czupryniak L, Małecki M. Diabetes mellitus. In: Witek P, editor. Diabetic autonomic neuropathy. Ed.2. Gdansk; 2016. p. 667.
37. Feldman M, Smith HJ. Effect of cisapride on gastric emptying of indigestible solids in patients with gastroparesis diabeticorum. A comparison with metoclopramide and placebo. Gastroenterology. 1987; 92:171.
38. Chen L, Zhang XF, Ku BQ, Wang XC, Ma C, Liang JY, Liu J.Effects of acupoint injection of autologous blood on symptoms and plasma motilin and gastrin levels of diabetic gastroparesis patients. Zhen Ci Yan Jiu. 2012;37(3):229–232, 246.
39. Gumaste V, Baum J. Treatment of gastroparesis: an update. Digestion. 2008;78: 173–179.
40. Guerci B, Bourgeois C, Bresler L, Scherrer ML, Böhme P. Gastric electrical stimulation for the treatment of diabetic gastroparesis. Diabetes Metab. 2012 Nov;38(5):393–402. doi: 10.1016/j.diabet.2012.05.001. Epub 2012 Jun 27.
41. Heckert J, Sankineni A, Hughes WB, Harbison S, Parkman H.Gastric Electric Stimulation for Refractory Gastroparesis: A Prospective Analysis of 151 Patients at a Single Center. Dig Dis Sci. 2016;61(1):168– 175. doi: 10.1007/s10620–015–3837-z. Epub 2015 Aug 18.
42. Chiu JD, Soffer E. Gastric electrical stimulation for obesity. Curr Gastroenterol Rep. 2015; 17: 424.
43. Khashab MA, Besharati S, Ngamruengphong S, et al. Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation (with video). Gastrointest Endosc. 2015; 82:1106.
44. Bhayani NH, Sharata AM, Dunst CM, Kurian AA, Reavis KM, Swanstrom LL.End of the road for a dysfunctional end organ: laparoscopic gastrectomy for refractory gastroparesis. J Gastrointest Surg. 2015;19(3):411–417. doi: 10.1007/s11605–014–2609-y. Epub 2015 Jan 10.
45. Wang CP, Kao CH, Chen WK, et al. A single-blinded, randomized pilot study evaluating effects of electroacupuncture in diabetic patients with symptoms suggestive of gastroparesis. J Altern Complement Med. 2008; 14:833.
46. Sieradzki J, Czupryniak L, Małecki M. Diabetes mellitus. In: Witek P, editor. Diabetic autonomic neuropathy. Ed.2. Gdansk; 2016. p. 674–677.