Mechanism and treatment of pancreatic endocrine and exocrine insufficiency in chronic pancreatitis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HOU Shengzhong , LONG Hairuo ,  TIAN Bole

Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

TIAN Bole, Email: hxtbl0338@126.com

Keywords：

chronic pancreatitis; endocrine insufficiency; exocrine insufficiency; mechanism

DOI：

10.7507/1007-9424.201806038

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To summarize current research advances of mechanism and treatment of pancreatic endocrine and exocrine insufficiency in chronic pancreatitis. Method The related literatures about the research progress of the pancreatic endocrine and exocrine insufficiency in the chronic pancreatitis in recent years were retrieved and reviewed. Results In recent years, it had many new studies and discoveries on the pancreatic endocrine and exocrine insufficiency in the chronic pancreatitis. The mechanism of the pancreatic exocrine dysfunction was mainly due to the decrease of the pancreatin secretion in the patients with chronic pancreatitis. The mechanism of the pancreatic endocrine insufficiency was mainly due to the damage of the pancreatic exocrine gland and islet tissue in the chronic pancreas, which leaded to the destruction of the pancreatic endocrine cells, the other endocrine cells, and the disturbance of the intestine-islet axis, followed by the disorder of the various hormones (insulin, glucagon, pancreatic polypeptide, etc.), and eventually manifested the glucose tolerance or dominant diabetes. Conclusions At present, although there is a certain degree understanding for pancreatic endocrine and exocrine insufficiency in chronic pancreatitis, there are no breakthroughs in its mechanism and treatment, and effect is lack of large sample and multicenter clinical control study. Exploring more optimized detection methods and establishing a perfect treatment system is goal of future development and research.

Citation： HOU Shengzhong, LONG Hairuo, TIAN Bole. Mechanism and treatment of pancreatic endocrine and exocrine insufficiency in chronic pancreatitis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(12): 1521-1526. doi: 10.7507/1007-9424.201806038 Copy

1.	Braganza JM, Lee SH, McCloy RF, et al. Chronic pancreatitis. Lancet, 2011, 377(9772): 1184-1197.
2.	《中华胰腺病杂志》编委会. 中国胰腺外分泌功能不全诊治规范 (草案). 中华胰腺病杂志, 2013, 13(1): 45-48.
3.	Keller J, Aghdassi AA, Lerch MM, et al. Tests of pancreatic exocrine function—clinical significance in pancreatic and non-pancreatic disorders. Best Pract Res Clin Gastroenterol, 2009, 23(3): 425-439.
4.	DiMagno EP, Malagelada JR, Go VL. Relationship between alcoholism and pancreatic insufficiency. Ann N Y Acad Sci, 1975, 252: 200-207.
5.	Keller J, Layer P. Human pancreatic exocrine response to nutrients in health and disease. Gut, 2005, 54(Suppl 6): v1-v28.
6.	Carrière F, Laugier R, Barrowman JA, et al. Gastric and pancreatic lipase levels during a test meal in dogs. Scand J Gastroenterol, 1993, 28(5): 443-454.
7.	Layer P, Go VL, DiMagno EP. Fate of pancreatic enzymes during small intestinal aboral transit in humans. Am J Physiol, 1986, 251(4 Pt 1): G475-G480.
8.	Nakamura T, Takeuchi T, Tando Y. Pancreatic dysfunction and treatment options. Pancreas, 1998, 16(3): 329-336.
9.	Dutta SK, Bustin MP, Russell RM, et al. Deficiency of fat-soluble vitamins in treated patients with pancreatic insufficiency. Ann Intern Med, 1982, 97(4): 549-552.
10.	Johnson EJ, Krasinski SD, Howard LJ, et al. Evaluation of vitamin A absorption by using oil-soluble and water-miscible vitamin A preparations in normal adults and in patients with gastrointestinal disease. Am J Clin Nutr, 1992, 55(4): 857-864.
11.	Nakamura T, Takebe K, Imamura K, et al. Fat-soluble vitamins in patients with chronic pancreatitis (pancreatic insufficiency). Acta Gastroenterol Belg, 1996, 59(1): 10-14.
12.	Teichmann J, Mann ST, Stracke H, et al. Alterations of vitamin D3 metabolism in young women with various grades of chronic pancreatitis. Eur J Med Res, 2007, 12(8): 347-350.
13.	Dujsikova H, Dite P, Tomandl J, et al. Occurrence of metabolic osteopathy in patients with chronic pancreatitis. Pancreatology, 2008, 8(6): 583-586.
14.	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): 226-237.
15.	王瑞星, 吴万春. 继发于慢性胰腺炎的 3c 型糖尿病的诊断与治疗. 国际消化病杂志, 2015, 35(1): 39-41.
16.	Lin YK, Johnston PC, Arce K, et al. Chronic pancreatitis and diabetes mellitus. Curr Treat Options Gastroenterol, 2015, 13(3): 319-331.
17.	Schrader H, Menge BA, Schneider S, et al. Reduced pancreatic volume and beta-cell area in patients with chronic pancreatitis. Gastroenterology, 2009, 136(2): 513-522.
18.	Andersen DK. Mechanisms and emerging treatments of the metabolic complications of chronic pancreatitis. Pancreas, 2007, 35(1): 1-15.
19.	Hennig R, Kekis PB, Friess H, et al. Pancreatic polypeptide in pancreatitis. Peptides, 2002, 23(2): 331-338.
20.	Śliwińska-Mossoń M, Milnerowicz H. Distribution of pancreatic polypeptide-secreting endocrine cells in nondiabetic and diabetic cases. Appl Immunohistochem Mol Morphol, 2017, 25(6): 422-431.
21.	Meier JJ, Giese A. Diabetes associated with pancreatic diseases. Curr Opin Gastroenterol, 2015, 31(5): 400-406.
22.	Gómez-Cerezo J, Garcés MC, Codoceo R, et al. Postprandial glucose-dependent insulinotropic polypeptide and insulin responses in patients with chronic pancreatitis with and without secondary diabetes. Regul Pept, 1996, 67(3): 201-205.
23.	Waljee AK, Dimagno MJ, Wu BU, et al. Systematic review: pancreatic enzyme treatment of malabsorption associated with chronic pancreatitis. Aliment Pharmacol Ther, 2009, 29(3): 235-246.
24.	Taylor JR, Gardner TB, Waljee AK, et al. Systematic review: efficacy and safety of pancreatic enzyme supplements for exocrine pancreatic insufficiency. Aliment Pharmacol Ther, 2010, 31(1): 57-72.
25.	Layer P, Keller J. Lipase supplementation therapy: standards, alternatives, and perspectives. Pancreas, 2003, 26(1): 1-7.
26.	Domínguez-Muñoz JE, Iglesias-García J, Vilariño-Insua M, et al. 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol, 2007, 5(4): 484-488.
27.	Safdi M, Bekal PK, Martin S, et al. The effects of oral pancreatic enzymes (Creon 10 capsule) on steatorrhea: a multicenter, placebo-controlled, parallel group trial in subjects with chronic pancreatitis. Pancreas, 2006, 33(2): 156-162.
28.	Whitcomb DC, Lehman GA, Vasileva G, et al. Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. Am J Gastroenterol, 2010, 105(10): 2276-2286.
29.	Domínguez-Muñoz JE, Iglesias-García J. Oral pancreatic enzyme substitution therapy in chronic pancreatitis: is clinical response an appropriate marker for evaluation of therapeutic efficacy? JOP, 2010, 11(2): 158-162.
30.	Domínguez-Muñoz JE, Iglesias-García J, Iglesias-Rey M, et al. Optimising the therapy of exocrine pancreatic insufficiency by the association of a proton pump inhibitor to enteric coated pancreatic extracts. Gut, 2006, 55(7): 1056-1057.
31.	de la Iglesia-García D, Huang W, Szatmary P, et al. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. Gut, 2017, 66(8): 1354-1355.
32.	Witt H, Apte MV, Keim V, et al. Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology, 2007, 132(4): 1557-1573.
33.	Rodbard D. Continuous glucose monitoring: A review of successes, challenges, and opportunities. Diabetes Technol Ther, 2016, 18(Suppl 2): S3-S13.
34.	Slezak LA, Andersen DK. Pancreatic resection: effects on glucose metabolism. World J Surg, 2001, 25(4): 452-460.
35.	Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 2009, 32(1): 193-203.
36.	Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract, 2009, 15(6): 540-559.
37.	Drucker DJ, Sherman SI, Gorelick FS, et al. Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care, 2010, 33(2): 428-433.
38.	Malka D, Hammel P, Sauvanet A, et al. Risk factors for diabetes mellitus in chronic pancreatitis. Gastroenterology, 2000, 119(5): 1324-1332.
39.	Rebours V, Boutron-Ruault MC, Schnee M, et al. The natural history of hereditary pancreatitis: a national series. Gut, 2009, 58(1): 97-103.
40.	Scheuing N, Berger G, Bergis D, et al. Adherence to clinical care guidelines for cystic fibrosis-related diabetes in 659 German/Austrian patients. J Cyst Fibros, 2014, 13(6): 730-736.
41.	Knop FK, Vilsbøll T, Larsen S, et al. Increased postprandial responses of GLP-1 and GIP in patients with chronic pancreatitis and steatorrhea following pancreatic enzyme substitution. Am J Physiol Endocrinol Metab, 2007, 292(1): E324-E330.
42.	O’Keefe SJ, Cariem AK, Levy M. The exacerbation of pancreatic endocrine dysfunction by potent pancreatic exocrine supplements in patients with chronic pancreatitis. J Clin Gastroenterol, 2001, 32(4): 319-323.
43.	Bellin MD, Freeman ML, Gelrud A, et al. Total pancreatectomy and islet autotransplantation in chronic pancreatitis: recommendations from PancreasFest. Pancreatology, 2014, 14(1): 27-35.
44.	Basevi V, Di Mario S, Morciano C, et al. Comment on: American Diabetes Association. Standards of medical care in diabetes-2011. Diabetes Care 2011; 34(Suppl. 1): S11-S61. Diabetes Care, 2011, 34(5): e53.
45.	Iván G. The principles of the treatment of pancreatic diabetes. Orv Hetil, 2009, 150(6): 273-276.

1. Braganza JM, Lee SH, McCloy RF, et al. Chronic pancreatitis. Lancet, 2011, 377(9772): 1184-1197.
2. 《中华胰腺病杂志》编委会. 中国胰腺外分泌功能不全诊治规范 (草案). 中华胰腺病杂志, 2013, 13(1): 45-48.
3. Keller J, Aghdassi AA, Lerch MM, et al. Tests of pancreatic exocrine function—clinical significance in pancreatic and non-pancreatic disorders. Best Pract Res Clin Gastroenterol, 2009, 23(3): 425-439.
4. DiMagno EP, Malagelada JR, Go VL. Relationship between alcoholism and pancreatic insufficiency. Ann N Y Acad Sci, 1975, 252: 200-207.
5. Keller J, Layer P. Human pancreatic exocrine response to nutrients in health and disease. Gut, 2005, 54(Suppl 6): v1-v28.
6. Carrière F, Laugier R, Barrowman JA, et al. Gastric and pancreatic lipase levels during a test meal in dogs. Scand J Gastroenterol, 1993, 28(5): 443-454.
7. Layer P, Go VL, DiMagno EP. Fate of pancreatic enzymes during small intestinal aboral transit in humans. Am J Physiol, 1986, 251(4 Pt 1): G475-G480.
8. Nakamura T, Takeuchi T, Tando Y. Pancreatic dysfunction and treatment options. Pancreas, 1998, 16(3): 329-336.
9. Dutta SK, Bustin MP, Russell RM, et al. Deficiency of fat-soluble vitamins in treated patients with pancreatic insufficiency. Ann Intern Med, 1982, 97(4): 549-552.
10. Johnson EJ, Krasinski SD, Howard LJ, et al. Evaluation of vitamin A absorption by using oil-soluble and water-miscible vitamin A preparations in normal adults and in patients with gastrointestinal disease. Am J Clin Nutr, 1992, 55(4): 857-864.
11. Nakamura T, Takebe K, Imamura K, et al. Fat-soluble vitamins in patients with chronic pancreatitis (pancreatic insufficiency). Acta Gastroenterol Belg, 1996, 59(1): 10-14.
12. Teichmann J, Mann ST, Stracke H, et al. Alterations of vitamin D3 metabolism in young women with various grades of chronic pancreatitis. Eur J Med Res, 2007, 12(8): 347-350.
13. Dujsikova H, Dite P, Tomandl J, et al. Occurrence of metabolic osteopathy in patients with chronic pancreatitis. Pancreatology, 2008, 8(6): 583-586.
14. 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): 226-237.
15. 王瑞星, 吴万春. 继发于慢性胰腺炎的 3c 型糖尿病的诊断与治疗. 国际消化病杂志, 2015, 35(1): 39-41.
16. Lin YK, Johnston PC, Arce K, et al. Chronic pancreatitis and diabetes mellitus. Curr Treat Options Gastroenterol, 2015, 13(3): 319-331.
17. Schrader H, Menge BA, Schneider S, et al. Reduced pancreatic volume and beta-cell area in patients with chronic pancreatitis. Gastroenterology, 2009, 136(2): 513-522.
18. Andersen DK. Mechanisms and emerging treatments of the metabolic complications of chronic pancreatitis. Pancreas, 2007, 35(1): 1-15.
19. Hennig R, Kekis PB, Friess H, et al. Pancreatic polypeptide in pancreatitis. Peptides, 2002, 23(2): 331-338.
20. Śliwińska-Mossoń M, Milnerowicz H. Distribution of pancreatic polypeptide-secreting endocrine cells in nondiabetic and diabetic cases. Appl Immunohistochem Mol Morphol, 2017, 25(6): 422-431.
21. Meier JJ, Giese A. Diabetes associated with pancreatic diseases. Curr Opin Gastroenterol, 2015, 31(5): 400-406.
22. Gómez-Cerezo J, Garcés MC, Codoceo R, et al. Postprandial glucose-dependent insulinotropic polypeptide and insulin responses in patients with chronic pancreatitis with and without secondary diabetes. Regul Pept, 1996, 67(3): 201-205.
23. Waljee AK, Dimagno MJ, Wu BU, et al. Systematic review: pancreatic enzyme treatment of malabsorption associated with chronic pancreatitis. Aliment Pharmacol Ther, 2009, 29(3): 235-246.
24. Taylor JR, Gardner TB, Waljee AK, et al. Systematic review: efficacy and safety of pancreatic enzyme supplements for exocrine pancreatic insufficiency. Aliment Pharmacol Ther, 2010, 31(1): 57-72.
25. Layer P, Keller J. Lipase supplementation therapy: standards, alternatives, and perspectives. Pancreas, 2003, 26(1): 1-7.
26. Domínguez-Muñoz JE, Iglesias-García J, Vilariño-Insua M, et al. 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol, 2007, 5(4): 484-488.
27. Safdi M, Bekal PK, Martin S, et al. The effects of oral pancreatic enzymes (Creon 10 capsule) on steatorrhea: a multicenter, placebo-controlled, parallel group trial in subjects with chronic pancreatitis. Pancreas, 2006, 33(2): 156-162.
28. Whitcomb DC, Lehman GA, Vasileva G, et al. Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial. Am J Gastroenterol, 2010, 105(10): 2276-2286.
29. Domínguez-Muñoz JE, Iglesias-García J. Oral pancreatic enzyme substitution therapy in chronic pancreatitis: is clinical response an appropriate marker for evaluation of therapeutic efficacy? JOP, 2010, 11(2): 158-162.
30. Domínguez-Muñoz JE, Iglesias-García J, Iglesias-Rey M, et al. Optimising the therapy of exocrine pancreatic insufficiency by the association of a proton pump inhibitor to enteric coated pancreatic extracts. Gut, 2006, 55(7): 1056-1057.
31. de la Iglesia-García D, Huang W, Szatmary P, et al. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. Gut, 2017, 66(8): 1354-1355.
32. Witt H, Apte MV, Keim V, et al. Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology, 2007, 132(4): 1557-1573.
33. Rodbard D. Continuous glucose monitoring: A review of successes, challenges, and opportunities. Diabetes Technol Ther, 2016, 18(Suppl 2): S3-S13.
34. Slezak LA, Andersen DK. Pancreatic resection: effects on glucose metabolism. World J Surg, 2001, 25(4): 452-460.
35. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 2009, 32(1): 193-203.
36. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract, 2009, 15(6): 540-559.
37. Drucker DJ, Sherman SI, Gorelick FS, et al. Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care, 2010, 33(2): 428-433.
38. Malka D, Hammel P, Sauvanet A, et al. Risk factors for diabetes mellitus in chronic pancreatitis. Gastroenterology, 2000, 119(5): 1324-1332.
39. Rebours V, Boutron-Ruault MC, Schnee M, et al. The natural history of hereditary pancreatitis: a national series. Gut, 2009, 58(1): 97-103.
40. Scheuing N, Berger G, Bergis D, et al. Adherence to clinical care guidelines for cystic fibrosis-related diabetes in 659 German/Austrian patients. J Cyst Fibros, 2014, 13(6): 730-736.
41. Knop FK, Vilsbøll T, Larsen S, et al. Increased postprandial responses of GLP-1 and GIP in patients with chronic pancreatitis and steatorrhea following pancreatic enzyme substitution. Am J Physiol Endocrinol Metab, 2007, 292(1): E324-E330.
42. O’Keefe SJ, Cariem AK, Levy M. The exacerbation of pancreatic endocrine dysfunction by potent pancreatic exocrine supplements in patients with chronic pancreatitis. J Clin Gastroenterol, 2001, 32(4): 319-323.
43. Bellin MD, Freeman ML, Gelrud A, et al. Total pancreatectomy and islet autotransplantation in chronic pancreatitis: recommendations from PancreasFest. Pancreatology, 2014, 14(1): 27-35.
44. Basevi V, Di Mario S, Morciano C, et al. Comment on: American Diabetes Association. Standards of medical care in diabetes-2011. Diabetes Care 2011; 34(Suppl. 1): S11-S61. Diabetes Care, 2011, 34(5): e53.
45. Iván G. The principles of the treatment of pancreatic diabetes. Orv Hetil, 2009, 150(6): 273-276.

Previous Article
Animal models for ALPPS: achievements and research development
Next Article
Research progress on relationship between galectin-1 and invasion and metastasis of gastric cancer

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Mechanism and treatment of pancreatic endocrine and exocrine insufficiency in chronic pancreatitis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content