Advertisement

Clinical Manifestations

  • Ayah Oglat
  • Eamonn M. M. Quigley
Chapter
Part of the Clinical Gastroenterology book series (CG)

Abstract

Though a variety of upper gastrointestinal symptoms are common among diabetics, their true prevalence, relationships to diabetes control, and other complications as well as underlying upper gastrointestinal (GI) sensori-motor dysfunction are often unclear. For example, though esophageal dysmotility is common in diabetes, its clinical significance in terms of symptomatology or as an indicator of gastric motor dysfunction remains to be defined. Similarly, studies on the prevalence of gastroesophageal reflux disease among diabetics have arrived at conflicting conclusions regarding the true prevalence of this association; available data, in contrast, suggests that diabetics are at increased risk for the development of Barrett’s esophagus and esophageal cancer. Gastroparesis is the best known and most extensively studied of the upper GI complications of diabetes; here again relationships between symptoms, gastric emptying rate, and glycemia are complex and pose significant clinical challenges. Though traditionally ascribed to the effects of autonomic neuropathy, more recent studies have revealed a variety of morphological, ultrastructural, and functional abnormalities in the enteric neuromuscular apparatus.

Keywords

Diabetes mellitus Esophageal dysmotility Gastroesophageal reflux disease Esophageal candidiasis Gastroparesis Accelerated gastric emptying 

Abbreviations

BE

Barrett’s esophagus

GEPG

Gastroesophageal pressure gradient

GERD

Gastroesophageal reflux disease

GI

Gastrointestinal

HAART

Highly active antiretroviral therapy

HIV

Human immunodeficiency virus

ICC

Interstitial cells of Cajal

LES

Lower esophageal sphincter

LPR

Laryngopharyngeal reflux

NSAID

Nonsteroidal anti-inflammatory drug

PUD

Peptic ulcer disease

TNF

Tumor necrosis factor

References

  1. 1.
    Kinekawa F, Kubo F, Matsuda K, Kobayashi M, Furuta Y, Fujita Y, et al. Esophageal function worsens with long duration of diabetes. J Gastroenterol. 2008;43:338–44.PubMedCrossRefGoogle Scholar
  2. 2.
    Boland BS, Edelman SV, Wolosin JD. Gastrointestinal complications of diabetes. Endocrinol Metab Clin N Am. 2013;42:809–32.CrossRefGoogle Scholar
  3. 3.
    Horgan JH, Doyle JS. A comparative study of esophageal motility in diabetics with neuropathy. Chest. 1971;6:170–4.CrossRefGoogle Scholar
  4. 4.
    Faraj J, Melander O, Sundkvist G, Olsson R, Thorsson O, Ekberg O, et al. Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus. Diabet Med. 2007;24:1235–9.PubMedCrossRefGoogle Scholar
  5. 5.
    George NS, Rangan V, Geng Z, Khan F, Kichler A, Gabbard S, et al. Distribution of esophageal motor disorders in diabetic patients with dysphagia. J Clin Gastroenterol. 2017;51:890–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Gatopoulou A, Papanas N, Maltezos E. Diabetic gastrointestinal autonomic neuropathy: current status and new achievements for everyday clinical practice. Eur J Intern Med. 2012;23:499–505.PubMedCrossRefGoogle Scholar
  7. 7.
    Beaumont H, Boeckxstaens G. Recent developments in esophageal motor disorders. Curr Opin Gastroenterol. 2007;23:416–21.PubMedCrossRefGoogle Scholar
  8. 8.
    Zhao J-B, Frøkjær JB, Drewes AM, Ejskjaer N. Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus. World J Gastroenterol. 2006;12:2846–57.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Zeng YJ, Yang J, Zhao JB, Liao DH, Zhang EP, Gregersen HA, et al. Morphologic and biomechanical changes of rat oesophagus in experimental diabetes. World J Gastroenterol. 2004;10:2519–23.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Frøkjaer JB, Brock C, Brun J, Simren M, Dimcevski G, Funch-Jensen P, et al. Esophageal distension parameters as potential biomarkers of impaired gastrointestinal function in diabetes patients. Neurogastroenterol Motil. 2012;24:1016–e544.PubMedCrossRefGoogle Scholar
  11. 11.
    Frokjaer JB, Andersen SD, Ejskjaer N, Funch-Jensen P, Drewes AM, Gregersen H. Impaired contractility and remodeling of the upper gastrointestinal tract in diabetes mellitus type-1. World J Gastroenterol. 2007;13(36):4881–90.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    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 getinopathy. Rev Diabet Stud. 2011;8:268–75.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Holloway RH, Tippett MD, Horowitz M, Maddox AF, Moten J, Russo A. Relationship between esophageal motility and transit in patients with type I diabetes mellitus. Am J Gastroenterol. 1999;94:3150–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Horowitz M, Maddox AF, Wishart JM, Harding PE, Chatterton BE, Shearman DJ. Relationships between oesophageal transit and solid and liquid gastric emptying in diabetes mellitus. Eur J Nucl Med. 1991;18:229–34.PubMedCrossRefGoogle Scholar
  16. 16.
    Jorge JX, Panão EA, Simões MA, Borges CI, Delgado FJ, Coelho AC, et al. Esophageal body motility in people with diabetes: comparison with non-diabetic healthy individuals. Diabetes Res Clin Pract. 2012;97:77–81.PubMedCrossRefGoogle Scholar
  17. 17.
    Loo FD, Dodds WJ, Soergel KH, Arndorfer RC, Helm JF, Hogan WJ. Multipeaked esophageal peristaltic pressure waves in patients with diabetic neuropathy. Gastroenterology. 1985;88:485–91.PubMedCrossRefGoogle Scholar
  18. 18.
    Roman S, Marjoux S, Thivolet C, Mion F. Oesophageal function assessed by high-resolution manometry in patients with diabetes and inadequate glycaemic control. Diabet Med. 2014;31:1452–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R, Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–20.PubMedCrossRefGoogle Scholar
  20. 20.
    Revicki DA, Wood M, Maton PN, Sorensen S. The impact of gastroesophageal reflux disease on health-related quality of life. Am J Med. 1998;104:252–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Promberger R, Lenglinger J, Riedl O, Seebacher G, Eilenberg W, Ott J, et al. Gastro-oesophageal reflux disease in type 2 diabetics: symptom load and pathophysiologic aspects—a retro-pro study. BMC Gastroenterol. 2013;13:132.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Punjabi P, Hira A, Prasad S, Wang X, Chokhavatia S. Review of gastroesophageal reflux disease (GERD) in the diabetic patient. J Diabetes. 2015;7:599–609.PubMedCrossRefGoogle Scholar
  23. 23.
    El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014;63:871–80.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Jansson C, Nordenstedt H, Wallander MA, Johansson S, Johnsen R, Hveem K, et al. Severe symptoms of gastro-oesophageal reflux disease are associated with cardiovascular disease and other gastrointestinal symptoms, but not diabetes: a population-based study. Aliment Pharmacol Ther. 2008;27:58–65.PubMedCrossRefGoogle Scholar
  25. 25.
    Ruigómez A, García Rodríguez LA, Wallander MA, Johansson S, Graffner H, Dent J. Natural history of gastro-oesophageal reflux disease diagnosed in general practice. Aliment Pharmacol Ther. 2004;20:751–60.PubMedCrossRefGoogle Scholar
  26. 26.
    Ha JO, Lee TH, Lee CW, Park JY, Choi SH, Lee JS, et al. Prevalence and risk factors of gastroesophageal reflux disease in patients with type 2 diabetes mellitus. Diabetes Metab J. 2016;40:297–307.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Lluch I, Ascaso JF, Mora F, Minguez M, Pena A, Hernandez A, et al. Gastroesophageal reflux in diabetes mellitus. Am J Gastroenterol. 1999;94:919–24.PubMedCrossRefGoogle Scholar
  28. 28.
    Nishida T, Tsuji S, Tsujii M, Arimitsu S, Sato T, Haruna Y, et al. Gastroesophageal reflux disease related to diabetes: analysis of 241 cases with type 2 diabetes mellitus. J Gastroenterol Hepatol. 2004;19:258–65.PubMedCrossRefGoogle Scholar
  29. 29.
    Moraes-Filho JPP, Navarro-Rodriguez T, Eisig JN, Barbuti RC, Chinzon D, et al. Comorbidities are frequent in patients with gastroesophageal reflux disease in a tertiary health care hospital. Clinics. 2009;64:785–90.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Hirata A, Kishida K, Nakatsuji H, Inoue K, Hiuge-Shimizu A, Funahashi T, et al. High prevalence of gastroesophageal reflux symptoms in type 2 diabetics with hypoadiponectinemia and metabolic syndrome. Nutr Metab (Lond). 2012;9:4.CrossRefGoogle Scholar
  31. 31.
    El-Serag HB, Graham DY, Satia JA, Rabeneck L. Obesity is an independent risk factor for GERD symptoms and erosive esophagitis. Am J Gastroenterol. 2005;100:1243–50.PubMedCrossRefGoogle Scholar
  32. 32.
    Ikeda Y, Furukawa S, Sakai T, Niiya T, Miyaoka H, Miyake T, Yamamoto S, et al. Age and prevalence of esophageal reflux disease in Japanese patients with type 2 diabetes mellitus: the Dogo study. Dig Dis Sci. 2016;61:3530–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Sun X-M, Tan JC, Zhu Y, Lin L. Association between diabetes mellitus and gastroesophageal reflux disease: a meta-analysis. World J Gastroenterol. 2015;21:3085–92.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Sun H, Yi L, Wu P, Li Y, Luo B, Xu S. Prevalence of gastroesophageal reflux disease in type II diabetes mellitus. Gastroenterol Res Pract. 2014;2014:601571.PubMedPubMedCentralGoogle Scholar
  35. 35.
    El-Serag H, Hill C, Jones BR. Systematic review: the epidemiology of gastro-oesophageal reflux in primary care, using the UK General Practice Database. Aliment Pharmacol Ther. 2009;29:470–80.PubMedCrossRefGoogle Scholar
  36. 36.
    Natalini J, Palit A, Sankineni A, Friedenberg FK. Diabetes mellitus is an independent risk for gastroesophageal reflux disease among urban African Americans. Dis Esophagus. 2015;28:405–11.PubMedCrossRefGoogle Scholar
  37. 37.
    Iyer PG, Borah BJ, Heien HC, Das A, Cooper GS, Chak A. Association of Barrett’s esophagus with type II diabetes mellitus: results from a large population-based case-control study. Clin Gastroenterol Hepatol. 2013;11:1108–14.PubMedCrossRefGoogle Scholar
  38. 38.
    Drahos J, Li L, Jick SS, Cook MB. Metabolic syndrome in relation to Barrett’s esophagus and esophageal adenocarcinoma: results from a large population-based case-control study in the Clinical Practice Research Data link. Cancer Epidemiol. 2016;42:9–14.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Rubenstein JH, Morgenstern H, McConell D, Scheiman JM, Schoenfeld P, Appelman H, et al. Associations of diabetes mellitus, insulin, leptin, and ghrelin with gastroesophageal reflux and Barrett’s esophagus. Gastroenterology. 2013;145:1237–44.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Cheng KC, Chen YL, Lai SW, Tsai PY, Sung FC. Risk of esophagus cancer in diabetes mellitus: a population-based case-control study in Taiwan. BMC Gastroenterol. 2012;12:177.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Dixon JL, Copeland LA, Zeber JE, MacCarthy AA, Reznik SI, Smythe WR, et al. Association between diabetes and esophageal cancer, independent of obesity, in the United States Veterans Affairs population. Dis Esophagus. 2016;29:747–51.PubMedCrossRefGoogle Scholar
  42. 42.
    Hamdan AL, Jabbour J, Barazi R, Korban Z, Azar ST. Prevalence of laryngopharyngeal reflux disease in patients with diabetes mellitus. J Voice. 2013;27:495–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Lee Y, McColl KEL. Pathophysiology of gastroesophageal reflux disease. Best Pract Res Clin Gastroenterol. 2013;27:339–51.PubMedCrossRefGoogle Scholar
  44. 44.
    Fornari F, Madalosso CA, Farré R, Gurski RR, Thiesen V, Callegari-Jacques SM. The role of gastro-oesophageal pressure gradient and sliding hiatal hernia on pathological gastro-oesophageal reflux in severely obese patients. Eur J Gastroenterol Hepatol. 2010;22:404–11.PubMedCrossRefGoogle Scholar
  45. 45.
    Zhao J, Gregersen H. Diabetes-induced mechanophysiological changes in the esophagus. Ann N Y Acad Sci. 2016;1380:139–54.PubMedCrossRefGoogle Scholar
  46. 46.
    Lauffer A, Forcelini CM, Ruas LO, Madalosso CA, Fornari F. Gastroesophageal reflux disease is inversely related with glycemic control in morbidly obese patients. Obes Surg. 2011;21:864–70.PubMedCrossRefGoogle Scholar
  47. 47.
    Uysal S, Kerur B, Shapiro JM, Snelling LK, Quintos JB. Acute erosive esophagitis as a rare complication of severe pediatric diabetes ketoacidosis. J Pediatr Gastroenterol Nutr. 2016;62:e38–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Asayama N, Nagata N, Shimbo T, Nishimura S, Igari T, Akiyama J, et al. Relationship between clinical factors and severity of esophageal candidiasis according to Kodsis classification. Dis Esophagus. 2013;27:214–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Takahashi Y, Nagata N, Shimbo T, Nishijima T, Watanabe K, Aoki T, et al. Long-term trends in esophageal candidiasis prevalence and associated risk factors with or without HIV infection: lessons from an endoscopic study of 80,219 patients. PLoS One. 2015;10:e0133589.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L, American College of Gastroenterology. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2012;108:18–37.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Khoo J, Rayner CK, Jones KL, Horowitz M. Pathophysiology and management of gastroparesis. Expert Rev Gastroenterol Hepatol. 2009;3:167–81.PubMedCrossRefGoogle Scholar
  52. 52.
    Heetun Z, Quigley EMM. Gastroparesis and Parkinson’s disease: a systematic review. Parkinsonism Relat Disord. 2012;18:433–40.PubMedCrossRefGoogle Scholar
  53. 53.
    Quigley EM. Other forms of gastroparesis: postsurgical, Parkinson, other neurologic diseases, connective tissue disorders. Gastroenterol Clin N Am. 2015;44:69–81.CrossRefGoogle Scholar
  54. 54.
    Jones KL, Russo A, Berry MK, Stevens JE, Wishart JM, Horowitz M. A longitudinal study of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus. Am J Med. 2002;113:449–55.PubMedCrossRefGoogle Scholar
  55. 55.
    Chang J, Rayner CK, Jones KL, Horowitz M. Prognosis of diabetic gastroparesis—a 25-year evaluation. Diabet Med. 2013;30:e185–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Koch KL, Hasler WL, Yates KP, Parkman HP, Pasricha PJ, Calles-Escandon J, et al. Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes. Neurogastroenterol Motil. 2016;28:1001–15.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Vanormelingen C, Tack J, Andrews CN. Diabetic gastroparesis. Br Med Bull. 2013;105:213–30.PubMedCrossRefGoogle Scholar
  58. 58.
    Bouras EP, Vazquez Roque MI, Aranda-Michel J. Gastroparesis. Nutr Clin Pract. 2013;28:437–47.PubMedCrossRefGoogle Scholar
  59. 59.
    Parkman HP, Hallinan EK, Hasler WL, Farrugia G, Koch KL, Calles J, et al. Nausea and vomiting in gastroparesis: similarities and differences in idiopathic and diabetic gastroparesis. Neurogastroenterol Motil. 2016;28:1902–14.PubMedCrossRefGoogle Scholar
  60. 60.
    Koduru P, Irani M, Quigley EMM. Definition, pathogenesis and management of that cursed dyspepsia. Clin Gastroenterol Hepatol. 2017.  https://doi.org/10.1016/j.cgh.2017.09.002. [epub ahead of print].
  61. 61.
    Talley NJ, 3rd Locke GR, Lahr BD, Zinsmeister AR, Tougas G, Ligozio G, et al. Functional dyspepsia, delayed gastric emptying, and impaired quality of life. Gut. 2006;55:933–9.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Chang J, Rayner CK, Jones KL, Horowitz M. Diabetic gastroparesis-backwards and forwards. J Gastroenterol Hepatol. 2011;26:46–57.PubMedCrossRefGoogle Scholar
  63. 63.
    Stanghellini V, Tack J. Gastroparesis: separate entity or just a part of dyspepsia? Gut. 2014;63:1972–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Shin AS, Camilleri M. Diagnostic assessment of diabetic gastroparesis. Diabetes. 2013;62:2667–73.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Parkman HP, Hallinan EK, Hasler WL, Farrugia G, Koch KL, Nguyen L, et al. Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing. Neurogastroenterol Motil. 2017;29.  https://doi.org/10.1111/nmo.12981. [epub ahead of print].
  66. 66.
    Hasler WL, Parkman HP, Wilson LA, Pasricha PJ, Koch KL, Abell TL, et al. Psychological dysfunction is associated with symptom severity but not disease etiology or degree of gastric retention in patients with gastroparesis. Am J Gastroenterol. 2010;105:2357–67.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Pasricha PJ, Yates KP, Nguyen L, Clarke J, Abell TL, Farrugia G, et al. Outcomes and factors associated with reduced symptoms in patients with gastroparesis. Gastroenterology. 2015;149:1762–74.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Chang J, Rayner CK, Jones KL, Horowitz M. Diabetic gastroparesis and its impact on glycemia. Endocrinol Metab Clin N Am. 2010;39:745–62.CrossRefGoogle Scholar
  69. 69.
    Homko C, Siraj ES, Parkman HP. The impact of gastroparesis on diabetes control: patient perceptions. J Diabetes Complicat. 2016;30:826–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Parkman HP, Yates KP, Hasler WL, Nguyan L, Pasricha PJ, Snape WJ, et al. Dietary intake and nutritional deficiencies in patients with diabetic or idiopathic gastroparesis. Gastroenterology. 2011;141:486–98.PubMedCrossRefGoogle Scholar
  71. 71.
    Jung HK, Choung RS, 3rd Locke GR, Schleck CD, Zinsmeister AR, Szarka LA, et al. The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology. 2009;136:1225–33.PubMedCrossRefGoogle Scholar
  72. 72.
    Camilleri M, Bharucha AE, Farrugia G. Epidemiology, mechanisms, and management of diabeticgastroparesis. Clin Gastroenterol Hepatol. 2011;9:5–12.PubMedCrossRefGoogle Scholar
  73. 73.
    Parkman HP, Yates K, Hasler WL, Nguyen L, Pasricha PJ, Snape WJ, et al. Clinical features of idiopathic gastroparesis vary with sex, bodymass, symptom onset, delay in gastric emptying, and gastroparesis severity. Gastroenterology. 2011;140:101–15.PubMedCrossRefGoogle Scholar
  74. 74.
    Gangula PR, Maner WL, Micci MA, Garfield RE, Pasricha PJ. Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. Am J Physiol Gastrointest Liver Physiol. 2007;292:G725–33.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Choung RS, 3rd Locke GR, Schleck CD, Zinsmeister AR, 3rd Melton LJ, Talley NJ. Risk of gastroparesis in subjects with type 1 and 2 diabetes in the general population. Am J Gastroenterol. 2012;107:82–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Wang YR, Fisher RS, Parkman HP. Gastroparesis-related hospitalizations in the United States: trends, characteristics, and outcomes, 1995-2004. Am J Gastroenterol. 2008;103:313–22.PubMedCrossRefGoogle Scholar
  77. 77.
    Rajan E, Gostout CJ, Wong Kee Song LM, Szarka LA, Kashyap PC, Smyrk TC, et al. Innovative gastric endoscopic muscle biopsy to identify all cell types, including myenteric neurons and interstitial cells of Cajal in patients with idiopathic gastroparesis: a feasibility study (with video). Gastrointest Endosc. 2016;84:512–7.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Grover M, Farrugia G, Lurken MS, Bernard CE, Faussone-Pellegrini MS, Smyrk TC, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011;140:1575–85.PubMedCrossRefGoogle Scholar
  79. 79.
    Grover M, Bernard CE, Pasricha PJ, Parkman HP, Gibbons SJ, Tonascia J, et al. Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum. Neurogastroenterol Motil. 2017;29.  https://doi.org/10.1111/nmo.13018. [epub ahead of print].
  80. 80.
    Eisenman ST, Gibbons SJ, Verhulst PJ, Cipriani G, Saur D, Farrugia G. Tumor necrosis factor alpha derived from classically activated “M1” macrophages reduces interstitial cell of Cajal numbers. Neurogastroenterol Motil. 2017;29.  https://doi.org/10.1111/nmo.12984. [epub ahead of print].
  81. 81.
    Faussone-Pellegrini MS, Grover M, Pasricha PJ, Bernard CE, Lurken MS, Smyrk TC, et al. Ultrastructural differences between diabetic and idiopathic gastroparesis. J Cell Mol Med. 2012;16:1573–81.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Grover M, Bernard CE, Pasricha PJ, Lurken MS, Faussone-Pellegrini MS, Smyrk TC, et al. Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium. Neurogastroenterol Motil. 2012;24:531–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Rivera LR, Poole DP, Thacker M, Furness JB. The involvement of nitric oxide synthase neurons in enteric neuropathies. Neurogastroenterol Motil. 2011;23:980–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Ordog T, Takayama I, Cheung WK. Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis. Diabetes. 2000;49:1731–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Watkins CC, Sawa A, Jaffrey S. Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy. J Clin Invest. 2000;106:373–84.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Gibbons SJ, Grover M, Choi KM, Wadhwa A, Zubair A, Wilson LA, Wu Y, et al. Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and idiopathic gastroparesis. PLoS One. 2017;12:e0187772.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Choi KM, Gibbons SJ, Sha L, Beyder A, Verhulst PJ, Cipriani G, et al. Interleukin 10 restores gastric emptying, electrical activity, and interstitial cells of Cajal networks in diabetic mice. Cell Mol Gastroenterol Hepatol. 2016;2:454–67.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Balan K, Sonoda LI, Seshadri N, Solanki C, Middleton S. Clinical significance of scintigraphic rapid gastric emptying. Nucl Med Commun. 2011;32:1185–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Phillips WT, Schwartz JG, McMahan CA. Rapid gastric emptying of an oral glucose solution in type 2 diabetic patients. J Nucl Med. 1992;33:1496–500.PubMedGoogle Scholar
  90. 90.
    Frank JW, Saslow SB, Camilleri M, Thomforde GM, Dinneen S, Rizza RA. Mechanism of accelerated gastric emptying of liquids and hyperglycemia in patients with type II diabetes mellitus. Gastroenterology. 1995;109:755–65.PubMedCrossRefGoogle Scholar
  91. 91.
    Bharucha AE, Kudva Y, Basu A, Camilleri M, Low PA, Vella A, et al. Relationship between glycemic control and gastric emptying in poorly controlled type 2 diabetes. Clin Gastroenterol Hepatol. 2015;13:466–76.PubMedCrossRefGoogle Scholar
  92. 92.
    Hayashi Y, Toyomasu Y, Saravanaperumal SA, Bardsley MR, Smestad JA, Lorincz A, et al. Hyperglycemia increases interstitial cells of Cajal via MAPK1 and MAPK3 signaling to ETV1 and KIT, leading to rapid gastric emptying. Gastroenterology. 2017;153:521–35.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Bytzer P, Talley NJ, Leemon M, Young LJ, Jones MP, Horowitz M. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med. 2001;161:1989–96.PubMedCrossRefGoogle Scholar
  94. 94.
    Hammer J, Howell S, Bytzer P, Horowitz M, Talley NJ. Symptom clustering in subjects with and without diabetes mellitus: a population-based study of 15,000 Australian adults. Am J Gastroenterol. 2003;98:391–8.PubMedGoogle Scholar
  95. 95.
    Bytzer P, Talley NJ, Hammer J, Young LJ, Jones MP, Horowitz M. GI symptoms in diabetes mellitus are associated with both poor glycemic control and diabetic complications. Am J Gastroenterol. 2002;97:604–11.PubMedCrossRefGoogle Scholar
  96. 96.
    Yarandi SS, Srinivasan S. Diabetic gastrointestinal motility disorders and the role of enteric nervous system: current status and future directions. Neurogastroenterol Motil. 2014;26:611–24.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Lanas A, Chan FKL. Peptic ulcer disease. Lancet. 2017;390:613–24.PubMedCrossRefGoogle Scholar
  98. 98.
    Huang JQ, Sridhar S, Hunt RH. Role of helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet. 2002;359:14–22.PubMedCrossRefGoogle Scholar
  99. 99.
    Sato T, Kitahara F, Nakamura T, Kojima Y, Fujino MA. Peptic ulcer in patients with diabetes mellitus. Nihon Rinsho. 2002;60:1580–4.PubMedGoogle Scholar
  100. 100.
    Peng YL, Leu HB, Luo JC, et al. Diabetes is an independent risk factor for peptic ulcer bleeding: a nationwide population-based cohort study. J Gastroenterol Hepatol. 2013;28:1295–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Wei F, Lin X. Diabetes increases morbidity and mortality rates in peptic ulcer bleeding: an updated systematic review and meta-analysis. Turk J Gastroenterol. 2016;27:304–11.PubMedCrossRefGoogle Scholar
  102. 102.
    Leontiadis GI, Molloy-Bland M, Moayyedi P, Howden CW. Effect of comorbidity on mortality in patients with peptic ulcer bleeding: systematic review and meta-analysis. Am J Gastroenterol. 2013;108:331–45.PubMedCrossRefGoogle Scholar
  103. 103.
    Thomsen RW, Riis A, Christensen S, Nørgaard M, Sørensen HT. Diabetes and 30-day mortality from peptic ulcer bleeding and perforation: a Danish population-based cohort study. Diabetes Care. 2006;29:805–10.PubMedCrossRefGoogle Scholar
  104. 104.
    Li J-Z, Li J-Y, Wu T-F, Xu J-H, Huang C-Z, Chen D, et al. Helicobacter pylori infection is associated with type 2 diabetes, not type 1 diabetes: an updated meta-analysis. Gastroenterol Res Pract. 2017;2017:5715403.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Harsch IA, Brzozowski T, Bazela K, Konturek SJ, Kuharsky V, Pawlik T, et al. Impaired gastric ulcer healing in diabetic rats: role of heat shock protein, growth factors, prostaglandins and proinflammatory cytokines. Eur J Pharmacol. 2003;481:249–60.PubMedCrossRefGoogle Scholar
  106. 106.
    Brzozowska I, Targosz A, Sliwowski Z, Kwiecien S, Drozdowicz D, Pajdo R, et al. Healing of chronic gastric ulcers in diabetic rats treated with native aspirin, nitric oxide (NO)-derivative of aspirin and cyclooxygenase (COX)-2 inhibitor. J Physiol Pharmacol. 2004;55:773–90.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Lynda K. and David M. Underwood Center for Digestive Disorders, Division of Gastroenterology and HepatologyHouston Methodist HospitalHoustonUSA

Personalised recommendations