Skip to main content

Advertisement

SpringerLink
Log in

Diabetes and the Pancreatobiliary Diseases

  • Motility (H Parkman and R Schey, Section Editors)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Abstract

Purpose of Review

The emphasis of this review article is to bring to the forefront the spectrum of pancreatobiliary disorders and their association with diabetes. We hope to systematically discuss the link between diabetes and disorders of the pancreas including acute and chronic pancreatitis, as well as pancreatic cancer. We also hope to review and highlight the literature with respect to other cancers of the biliary tree including gallbladder and cholangiocarcinoma. Lastly, we discuss diabetes and biliary dyskinesia.

Recent Findings

Newer cohort studies suggest the presence of diabetes to increase the severity and worsen outcomes in acute pancreatitis. Post pancreatitis diabetes is a novel disease entity being increasingly recognized. The use of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis may attenuate the risk of endocrine dysfunction. Pancreatic cancer may either be the consequence of diabetes or a presenting manifestation. The use of anti-diabetic medications may confer protection against development of pancreatic cancer. Gallbladder adenocarcinoma and cholangiocarcinoma risks are elevated in those with underlying diabetes.

Summary

Diabetes can directly impact or deteriorate outcome of acute and chronic pancreatitis and well as pancreatobiliary malignancies. It could also occur as a result of loss of endocrine function after pancreatitis. Like many areas of the digestive tract, biliary motility could be impacted by diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References and Recommended Reading

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

  1. Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Localio SA. Objective early identification of severe acute pancreatitis. Am J Gastroenterol. 1974;61(6):443–51.

    CAS  PubMed  Google Scholar 

  2. Kikuta K, Masamune A, Shimosegawa T. Impaired glucose tolerance in acute pancreatitis. World J Gastroenterol. 2015;21(24):7367–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lai SW, Muo CH, Liao KF, Sung FC, Chen PC. Risk of acute pancreatitis in type 2 diabetes and risk reduction on anti-diabetic drugs: a population-based cohort study in Taiwan. Am J Gastroenterol. 2011;106(9):1697–704.

    Article  PubMed  Google Scholar 

  4. Gonzalez-Perez A, Schlienger RG, Rodríguez LA. Acute pancreatitis in association with type 2 diabetes and antidiabetic drugs: a population-based cohort study. Diabetes Care. 2010;33(12):2580–5.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Clemens DL, Schneider KJ, Arkfeld CK, Grode JR, Wells MA, Singh S. Alcoholic pancreatitis: new insights into the pathogenesis and treatment. World J Gastrointest Pathophysiol. 2016;7(1):48–58.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Shalbueva N, Mareninova OA, Gerloff A, et al. Effects of oxidative alcohol metabolism on the mitochondrial permeability transition pore and necrosis in a mouse model of alcoholic pancreatitis. Gastroenterology. 2013;144(2):437–446.e436.

    Article  CAS  PubMed  Google Scholar 

  7. Petrov MS, Shanbhag S, Chakraborty M, Phillips AR, Windsor JA. Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. Gastroenterology. 2010;139(3):813–20.

    Article  PubMed  Google Scholar 

  8. Larvin M, McMahon MJ. APACHE-II score for assessment and monitoring of acute pancreatitis. Lancet (London, England). 1989;2(8656):201–5.

    Article  CAS  Google Scholar 

  9. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–11.

    Article  PubMed  Google Scholar 

  10. Singh VK, Wu BU, Bollen TL, et al. A prospective evaluation of the bedside index for severity in acute pancreatitis score in assessing mortality and intermediate markers of severity in acute pancreatitis. Am J Gastroenterol. 2009;104(4):966–71.

    Article  PubMed  Google Scholar 

  11. •• Huh JH, Jeon H, Park SM, et al. Diabetes mellitus is associated with mortality in acute pancreatitis. J Clin Gastroenterol. 2016. https://doi.org/10.1097/MCG.0000000000000783.Major study showing worse outcomes in diabetic patients with acute pancreatitis

  12. Shen HN, Chang YH, Chen HF, Lu CL, Li CY. Increased risk of severe acute pancreatitis in patients with diabetes. Diabet Med. 2012;29(11):1419–24.

    Article  PubMed  Google Scholar 

  13. Uc A, Andersen DK, Bellin MD, et al. Chronic pancreatitis in the 21st century—research challenges and opportunities: summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop. Pancreas. 2016;45(10):1365–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. •• Das SL, Singh PP, Phillips AR, Murphy R, Windsor JA, Petrov MS. Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis. Gut. 2014;63(5):818–31. Large systematic review highlighting importance of recognizing post pancreatitis diabetes

    Article  PubMed  Google Scholar 

  15. • Nikkola J, Laukkarinen J, Lahtela J, et al. The long-term prospective follow-up of pancreatic function after the first episode of acute alcoholic pancreatitis: recurrence predisposes one to pancreatic dysfunction and pancreatogenic diabetes. J Clin Gastroenterol. 2017;51(2):183–90. Recent prospective study showing increased incidence of diabetes after episode of pancreatitis

    Article  PubMed  Google Scholar 

  16. Hart PA, Bellin MD, Andersen DK, et al. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. Lancet Gastroenterol Hepatol. 2016;1(3):226–37.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ewald N, Hardt PD. Diagnosis and treatment of diabetes mellitus in chronic pancreatitis. World J Gastroenterol. 2013;19(42):7276–81.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Pan J, Xin L, Wang D, et al. Risk factors for diabetes mellitus in chronic pancreatitis: a cohort of 2011 patients. Medicine (Baltimore). 2016;95(14):e3251.

    Article  Google Scholar 

  19. Rickels MR, Bellin M, Toledo FG, et al. Detection, evaluation and treatment of diabetes mellitus in chronic pancreatitis: recommendations from PancreasFest 2012. Pancreatology. 2013;13(4):336–42.

    Article  CAS  PubMed  Google Scholar 

  20. Wu Q, Zhang M, Qin Y, et al. Systematic review and meta-analysis of islet autotransplantation after total pancreatectomy in chronic pancreatitis patients. Endocr J. 2015;62(3):227–34.

    Article  PubMed  Google Scholar 

  21. Garcea G, Pollard CA, Illouz S, Webb M, Metcalfe MS, Dennison AR. Patient satisfaction and cost-effectiveness following total pancreatectomy with islet cell transplantation for chronic pancreatitis. Pancreas. 2013;42(2):322–8.

    Article  PubMed  Google Scholar 

  22. McAuliffe JC, Christein JD. Type 2 diabetes mellitus and pancreatic cancer. Surg Clin North Am. 2013;93(3):619–27.

    Article  PubMed  Google Scholar 

  23. Makhoul I, Yacoub A, Siegel E. Type 2 diabetes mellitus is associated with increased risk of pancreatic cancer: a veteran administration registry study. SAGE Open Med. 2016;4:2050312116682257.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Batabyal P, Vander Hoorn S, Christophi C, Nikfarjam M. Association of diabetes mellitus and pancreatic adenocarcinoma: a meta-analysis of 88 studies. Ann Surg Oncol. 2014;21(7):2453–62.

    Article  PubMed  Google Scholar 

  25. Song S, Wang B, Zhang X, et al. Long-term diabetes mellitus is associated with an increased risk of pancreatic cancer: a meta-analysis. PLoS One. 2015;10(7):e0134321.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lu Y, García Rodríguez LA, Malgerud L, et al. New-onset type 2 diabetes, elevated HbA1c, anti-diabetic medications, and risk of pancreatic cancer. Br J Cancer. 2015;113(11):1607–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Aggarwal G, Ramachandran V, Javeed N, et al. Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice. Gastroenterology. 2012;143(6):1510–1517.e1511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang Z, Lai ST, Xie L, et al. Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2014;106(1):19–26.

    Article  CAS  PubMed  Google Scholar 

  29. • Zhou PT, Li B, Liu FR, et al. Metformin is associated with survival benefit in pancreatic cancer patients with diabetes: a systematic review and meta-analysis. Oncotarget. 2017;8(15):25242–50. Recent cohort study showing preventative role of metformin in diabetics with pancreatic cancer

    PubMed  PubMed Central  Google Scholar 

  30. Zhou DC, Gong H, Tan CQ, Luo JQ. Prognostic significance of anti-diabetic medications in pancreatic cancer: A meta-analysis. Oncotarget. 2017;8(37):62349-57.

  31. Ren HB, Yu T, Liu C, Li YQ. Diabetes mellitus and increased risk of biliary tract cancer: systematic review and meta-analysis. Cancer Causes Control. 2011;22(6):837–47.

    Article  PubMed  Google Scholar 

  32. Schlesinger S, Aleksandrova K, Pischon T, et al. Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort. Ann Oncol. 2013;24(9):2449–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Saengboonmee C, Seubwai W, Wongkham C, Wongkham S. Diabetes mellitus: possible risk and promoting factors of cholangiocarcinoma: association of diabetes mellitus and cholangiocarcinoma. Cancer Epidemiol. 2015;39(3):274–8.

    Article  PubMed  Google Scholar 

  34. Li J, Han T, Xu L, Luan X. Diabetes mellitus and the risk of cholangiocarcinoma: an updated meta-analysis. Prz Gastroenterol. 2015;10(2):108–17.

    PubMed  PubMed Central  Google Scholar 

  35. Huang YJ, Wu AT, Chiou HY, et al. Interactive role of diabetes mellitus and female sex in the risk of cholangiocarcinoma: a population-based nested case-control study. Oncotarget. 2017;8(4):6642–51.

    PubMed  Google Scholar 

  36. Nordenstedt H, Mattsson F, El-Serag H, Lagergren J. Gallstones and cholecystectomy in relation to risk of intra- and extrahepatic cholangiocarcinoma. Br J Cancer. 2012 Feb 28;106(5):1011-5.

  37. Gitelson S, Oppenheim D, Schwartz A. Size of the gallbladder in patients with diabetes mellitus. Diabetes. 1969;18(7):493–8.

    Article  CAS  PubMed  Google Scholar 

  38. De Santis A, Attili AF, Ginanni Corradini S, et al. Gallstones and diabetes: a case-control study in a free-living population sample. Hepatology (Baltimore, Md). 1997;25(4):787–90.

    Article  Google Scholar 

  39. Attili AF, Capocaccia R, Carulli N, et al. Factors associated with gallstone disease in the MICOL experience. Multicenter Italian study on epidemiology of cholelithiasis. Hepatology (Baltimore, Md). 1997;26(4):809–18.

    Article  CAS  Google Scholar 

  40. Stone BG, Gavaler JS, Belle SH, et al. Impairment of gallbladder emptying in diabetes mellitus. Gastroenterology. 1988;95(1):170–6.

    Article  CAS  PubMed  Google Scholar 

  41. Shreiner DP, Sarva RP, Van Thiel D, Yingvorapant N. Gallbladder function in diabetic patients. J nucl med : off pub Soc Nucl Med. 1986;27(3):357–60.

    CAS  Google Scholar 

  42. Meguro T, Shimosegawa T, Satoh A, et al. Gallbladder emptying and cholecystokinin and pancreatic polypeptide responses to a liquid meal in patients with diabetes mellitus. J Gastroenterol. 1997;32(5):628–34.

    Article  CAS  PubMed  Google Scholar 

  43. Chapman BA, Chapman TM, Frampton CM, et al. Gallbladder volume: comparison of diabetics and controls. Dig Dis Sci. 1998;43(2):344–8.

    Article  CAS  PubMed  Google Scholar 

  44. Hahm JS, Park JY, Park KG, Ahn YH, Lee MH, Park KN. Gallbladder motility in diabetes mellitus using real time ultrasonography. Am J Gastroenterol. 1996;91(11):2391–4.

    CAS  PubMed  Google Scholar 

  45. Nakeeb A, Comuzzie AG, Al-Azzawi H, Sonnenberg GE, Kissebah AH, Pitt HA. Insulin resistance causes human gallbladder dysmotility. J gastrointest surg : off j Soc Surg Aliment Tract. 2006;10(7):940–8. discussion 948-949

    Article  Google Scholar 

  46. Kayacetin E, Kisakol G, Kaya A, Akpinar Z. Real-time sonography for screening of gallbladder motility in diabetic patients: relation to autonomic and peripheral neuropathy. Neuro endocrinology letters. 2003;24(1–2):73–6.

    PubMed  Google Scholar 

  47. Braverman DZ. The lack of effect of metoclopramide on gallbladder volume and contraction in diabetic cholecystoparesis. Am J Gastroenterol. 1986;81(10):960–2.

    CAS  PubMed  Google Scholar 

  48. Kronert K, Gotz V, Reuland P, Luft D, Eggstein M. Gallbladder emptying in diabetic patients and control subjects assessed by real-time ultrasonography and cholescintigraphy: a methodological comparison. Ultrasound Med Biol. 1989;15(6):535–9.

    Article  CAS  PubMed  Google Scholar 

  49. Fiorucci S, Scionti L, Bosso R, et al. Effect of erythromycin on gallbladder emptying in diabetic patients with and without autonomic neuropathy and high levels of motilin. Dig Dis Sci. 1992;37(11):1671–7.

    Article  CAS  PubMed  Google Scholar 

  50. Laakso M, Suhonen M, Julkunen R, Pyorala K. Plasma insulin, serum lipids and lipoproteins in gall stone disease in non-insulin dependent diabetic subjects: a case control study. Gut. 1990;31(3):344–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gielkens HA, van Oostayen JA, Frolich M, Biemond I, Lamers CB, Masclee AA. Dose-dependent inhibition of postprandial gallbladder motility and plasma hormone secretion during acute hyperglycemia. Scand J Gastroenterol. 1998;33(10):1074–9.

    Article  CAS  PubMed  Google Scholar 

  52. de Boer SY, Masclee AA, Jebbink MC, et al. Effect of acute hyperglycaemia on gall bladder contraction induced by cholecystokinin in humans. Gut. 1993;34(8):1128–32.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Mitsukawa T, Takemura J, Ohgo S, et al. Gallbladder function and plasma cholecystokinin levels in diabetes mellitus. Am J Gastroenterol. 1990;85(8):981–5.

    CAS  PubMed  Google Scholar 

  54. Arshad F, Laway BA, Rather TA, Kuchay MS, Khan SH. Impaired gallbladder motility in adults with newly detected type 2 diabetes and lack of reversibility after achieving euglycemia. Can J Diabetes. 2015;39(2):101–4.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastroenterology and Hepatology, Temple University Hospital, Philadelphia, PA, USA

    Muhammad Shafqet MD

  2. Division of Gastroenterology and Hepatology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, L461, Portland, OR, 97239, USA

    Kaveh Sharzehi MD, MS

Authors
  1. Muhammad Shafqet MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kaveh Sharzehi MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kaveh Sharzehi MD, MS.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

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.

Additional information

This article is part of the Topical Collection on Motility

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shafqet, M., Sharzehi, K. Diabetes and the Pancreatobiliary Diseases. Curr Treat Options Gastro 15, 508–519 (2017). https://doi.org/10.1007/s11938-017-0163-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11938-017-0163-x

Keywords

Search

Navigation