Keywords
diabetes mellitus, chronic pancreatitis, type 3c diabetes, pancreatogenic diabetes, pancreatitis
How to Cite
Ewald, N., & Hardt, P. D. (2017). Diagnosis and treatment of diabetes mellitus in chronic pancreatitis. Herald of Pancreatic Club, 37(4), 15-21. https://doi.org/10.33149/vkp.2017.04.02
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Abstract
Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus. It is a clinically relevant condition with a prevalence of 5-10% among all diabetic subjects in Western populations. In nearly 80% of all type 3c diabetes mellitus cases, chronic pancreatitis seems to be the underlying disease. The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far. In contrast to the management of type 1 or type 2 diabetes mellitus, the endocrinopathy in type 3c is very complex. The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition. General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus (up to 90% of all cases) is rather good. However, in a patient first presenting with diabetes mellitus, chronic pancreatitis as a potential causative condition is seldom considered. Thus many patients are misdiagnosed. The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy. In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency, preventing or treating a lack of fat-soluble vitamins (especially vitamin D) and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.
References
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8. Chronic pancreatitis-like changes detected by endoscopic ultrasound in subjects without signs of pancre¬atic disease: do these indicate age-related changes, effects of xenobiotics, or early chronic pancreatitis? / M. C. Petrone, P. G. Arcidiacono, F. Perri [et al.] // Pancreatology. – 2010. – Vol. 10. – P. 597–602.
9. Clinical and genetic characteristics of hereditary pancreatitis in Europe / N. Howes, M. M. Lerch, W. Greenhalf [et al.] // Clin. Gastroenterol. Hepatol. – 2004. – Vol. 2. – P. 252–261.
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11. Detection, evaluation and treatment of diabetes mellitus in chronic pancreatitis : recommendations from PancreasFest 2012 / Rickels MR, Bellin M, Toledo FG [et al.] // Pancreatology. – 2013. – Vol. 13. – P. 336–342.
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13. Ebert R. Reversal of impaired GIP and insulin secretion in patients with pancreatogenic steatorrhea following enzyme substitution / R. Ebert, W. Creutzfeldt // Diabetologia. – 1980. – Vol. 19. – P. 198–204.
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17. Fecal elastase 1 and vitamin D3 in patients with osteoporotic bone fractures / Mann ST, Mann V, Stracke H [et al.] // Eur J Med Res 2008. – Vol. 13. – P. 68–72.
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19. Gastric emptying, incretin hormone secretion, and postprandial glycemia in cystic fibrosis: effects of pancreatic enzyme supplementation / P. Kuo, J. E. Stevens, A. Russo [et al.] // J. Clin. Endocrinol. Metab. – 2011. – Vol. 96. – P. E851–E855.
20. Increased risk of acute pancreatitis and biliary disease observed in pa¬tients with type 2 diabetes : a retrospective cohort study / R. A. Noel, D. K. Braun, R. E. Patterson, G. L. Bloomgren // Dia¬betes Care. – 2009. – Vol. 32. – P. 834–838.
21. Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed? / P. D. Hardt, M. D. Brendel, H. U. Kloer, R. G. Bretzel // Diabetes Care. – 2008. – Vol. 31, Suppl 2. – P. S165–S169.
22. Klapdor S. Vitamin D status and peroral vitamin D supplementation in patients suffering from chronic pancreatitis and pancreatic cancer disease / S. Klapdor, E. Richter, R. Klapdor // Anticancer Res. – 2012. – Vol. 32. – P. 1991–1998.
23. Larsen S. Diabetes mellitus secondary to chronic pancreati¬tis / S. Larsen // Dan. Med. Bull. – 1993. – Vol. 40. – P. 153–162.
24. Magruder J. T. Diabetes and pancre¬atic cancer: chicken or egg? / J. T. Magruder, D. Elahi, D. K. Andersen // Pancreas. – 2011. – Vol. 40. – P. 339–351.
25. 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 / D. M. Nathan, J. B. Buse, M. B. Davidson [et al.] // Diabetes Care. – 2009. – Vol. 32. – P. 193–203.
26. Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis / S. Larsen, J. Hilsted, B. Tronier, H. Worning // Metabolism. – 1987. – Vol. 36. – P. 964–967.
27. Metformin use is associated with better survival of dia¬betic patients with pancreatic cancer / N. Sadeghi, J. L. Abbruzzese, S. C. Yeung [et al.] // Clin. Cancer Res. – 2012. – Vol. 18. – P. 2905–2912.
28. Mohan V. Tropical chronic pancreatitis / V. Mohan, C. Pitchumoni // The Pancreas / Eds. H. G. Beger, A. L. Warshaw, M. W. Buechler [et al.]. – London : Blackwell Science, 1998. – P. 688–697.
29. Occurrence of and risk factors for diabetes mellitus in Chinese patients with chronic pancreatitis / W. Wang, Y. Guo, Z. Liao // Pancreas. – 2011. – Vol. 40. – P. 206–212.
30. Olsen T. S. Lipomatosis of the pancreas in autopsy material and its relation to age and overweight / T. S. Olsen // Acta Pathol. Microbiol. Scand. A. – 1978. – Vol. 86A. – P. 367–373.
31. Pancreatic exocrine function in patients with type 1 and type diabetes mellitus / P. D. Hardt, A. Krauss, L. Bretz [et al.] // Acta Diabetol. – 2000. – Vol. 37. – P. 105–110.
32. Pancreatic hor¬mone secretion in chronic pancreatitis without residual beta¬cell function / S. Larsen, J. Hilsted, B. Tronier, H. Worning // Acta Endocrinol (Copenh). – 1988. – Vol. 118. – P. 357–364.
33. Pancreatic polypep¬tide response to secretin in obesity: effects of glucose intolerance / B. Glaser, G. Zoghlin, K. Pienta, A. I. Vinik // Horm. Metab. Res. – 1988. – Vol. 20. – P. 288–292.
34. Pancreatitis and pancreatic cancer risk : a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4) / E. J. Duell, E. Lucenteforte, S. H. Olson [et al.] // Ann. Oncol. – 2012. – Vol. 23. – P. 2964–2970.
35. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group / A. B. Lowenfels, P. Maisonneuve, G. Cavallini [et al.] // N. Engl. J. Med. – 1993. – Vol. 328. – P. 1433–1437.
36. Prevalence and determinants of exocrine pan¬creatic insufficiency among older adults : results of a population-based study / D. Rothenbacher, M. Löw, P. D. Hardt [et al.] // Scand. J. Gastroenterol. – 2005. – Vol. 40. – P. 697–704.
37. Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c) / N. Ewald, C. Kaufmann, A. Raspe [et al.] // Diabetes Metab. Res. Rev. – 2012. – Vol. 28. – P. 338–342.
38. Risk factors for diabetes mellitus in chronic pancreatitis / D. Malka, P. Hammel, A. Sauvanet [et al.] // Gastroen¬terology. – 2000. – Vol. 119. – P. 1324–1332.
39. Role of fat hydrolysis in regulating glucagon-like Peptide-1 secretion / S. Beglinger, J. Drewe, J. Schirra [et al.] // J. Clin. Endocrinol. Metab. – 2010. – Vol. 95. – P. 879–886.
40. Sikkens E. C. The prevalence of fat-soluble vitamin deficiencies and a decreased bone mass in patients with chronic pancreatitis / E. C. Sikkens, D. L. Cahen, A. D. Koch // Pancreatology. – 2013. – Vol. 13. – P. 238–242.
41. The Diabetes Control and Complications Trial (DCCT). Design and methodologic considerations for the feasibility phase. The DCCT Research Group // Diabetes. – 1986. – Vol. 35. – P. 530–545.
42. The natural history of hereditary pancreatitis : a national series / V. Rebours, M. C. Boutron-Ruault, M. Schnee [et al.] // Gut. – 2009. – Vol. 58. – P. 97–103.
43. Tropi¬cal or malnutrition-related diabetes: a real syndrome? / A. Abu-Bakare, R. Taylor, G. V. Gill, K. G. Alberti // Lancet. – 1986. – Vol. 1. – P. 1135–1138.
44. Type 1 diabetes mellitus associated with clinical acute pancreatitis in an adult / T. Moriai, Y. Morita, T. Matsui, M. Okada // Pancreas. – 2000. – Vol. 20. – P. 415–416.
45. UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance // Diabetologia. – 1991. – Vol. 34. – P. 877–890.
46. Valenzuela J. E. Pancreatic polypeptide response in patients with chronic pancreatitis / J. E. Valenzuela, I. L. Taylor, J. H. Walsh // Dig. Dis. Sci. – 1979. – Vol. 24. – P. 862–864.
2. Alterations of vitamin D3 metabolism in young women with various grades of chronic pancreatitis / J. Teichmann, S. T. Mann, H. Stracke [et al.] // Eur. J. Med. Res. – 2007. – Vol. 12. – P. 347–350.
3. Alves C. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer / C. Alves, F. Batel-Marques, A. F. Macedo // Diabetes Res. Clin. Pract. – 2012. – Vol. 98. – P. 271–284.
4. American Diabetes Association. Diagnosis and classifica¬tion of diabetes mellitus // Diabetes Care. – 2011. – Vol. 34, Suppl 1. – P. S62–S69.
5. Associations between concentrations of vitamin D and concentrations of insulin, glucose, and HbA1c among adolescents in the United States / E. S. Ford, G. Zhao, J. Tsai, C. Li // Diabetes Care. – 2011. – Vol. 34. – P. 646–648.
6. Blumenthal H. T. Interrelationship of diabetes mellitus and pancreatitis / H. T. Blumenthal, J. G. Probstein, A.W. Berns // Arch. Surg. – 1963. – Vol. 87. – P. 844–850.
7. Boucher B. J. Vitamin D insufficiency and diabetes risks / B. J. Boucher // Curr. Drug. Targets. – 2011. – Vol. 12. – P. 61–87.
8. Chronic pancreatitis-like changes detected by endoscopic ultrasound in subjects without signs of pancre¬atic disease: do these indicate age-related changes, effects of xenobiotics, or early chronic pancreatitis? / M. C. Petrone, P. G. Arcidiacono, F. Perri [et al.] // Pancreatology. – 2010. – Vol. 10. – P. 597–602.
9. Clinical and genetic characteristics of hereditary pancreatitis in Europe / N. Howes, M. M. Lerch, W. Greenhalf [et al.] // Clin. Gastroenterol. Hepatol. – 2004. – Vol. 2. – P. 252–261.
10. Cui Y. Pancreatogenic diabetes: special con¬siderations for management / Y. Cui, D. K. Andersen // Pancreatology. – 2011. – Vol. 11. – P. 279–294.
11. Detection, evaluation and treatment of diabetes mellitus in chronic pancreatitis : recommendations from PancreasFest 2012 / Rickels MR, Bellin M, Toledo FG [et al.] // Pancreatology. – 2013. – Vol. 13. – P. 336–342.
12. Doerr W. Pathogenesis of acute and chronic pancreatitis / W. Doerr // Verh. Dtsch. Ges. Inn. Med. – 1964. – Vol. 70. – P. 718–758.
13. Ebert R. Reversal of impaired GIP and insulin secretion in patients with pancreatogenic steatorrhea following enzyme substitution / R. Ebert, W. Creutzfeldt // Diabetologia. – 1980. – Vol. 19. – P. 198–204.
14. Etemad B. Chronic pancreatitis: diagnosis, classification, and new genetic developments / B. Etemad, D. C. Whitcomb // Gastroenter¬ology. – 2001. – Vol. 120. – P. 682–707.
15. Ewald N. Diabetes mellitus secondary to pan¬creatic diseases (Type 3c): are we neglecting an important disease? / N. Ewald, R. G. Bretzel // Eur. J. Intern. Med. – 2013. – Vol. 24. – P. 203–206.
16. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the di¬agnosis and classification of diabetes mellitus // Diabetes Care 2003. – Vol. 26, Suppl 1. – P. S5–S20.
17. Fecal elastase 1 and vitamin D3 in patients with osteoporotic bone fractures / Mann ST, Mann V, Stracke H [et al.] // Eur J Med Res 2008. – Vol. 13. – P. 68–72.
18. Ganda O. Secondary forms of diabetes / O. Ganda // Joslin’s Diabetes Mellitus // Eds. C. R. Kahn, G. C. Weir. – New York : Lea & Febiger, 1994.
19. Gastric emptying, incretin hormone secretion, and postprandial glycemia in cystic fibrosis: effects of pancreatic enzyme supplementation / P. Kuo, J. E. Stevens, A. Russo [et al.] // J. Clin. Endocrinol. Metab. – 2011. – Vol. 96. – P. E851–E855.
20. Increased risk of acute pancreatitis and biliary disease observed in pa¬tients with type 2 diabetes : a retrospective cohort study / R. A. Noel, D. K. Braun, R. E. Patterson, G. L. Bloomgren // Dia¬betes Care. – 2009. – Vol. 32. – P. 834–838.
21. Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed? / P. D. Hardt, M. D. Brendel, H. U. Kloer, R. G. Bretzel // Diabetes Care. – 2008. – Vol. 31, Suppl 2. – P. S165–S169.
22. Klapdor S. Vitamin D status and peroral vitamin D supplementation in patients suffering from chronic pancreatitis and pancreatic cancer disease / S. Klapdor, E. Richter, R. Klapdor // Anticancer Res. – 2012. – Vol. 32. – P. 1991–1998.
23. Larsen S. Diabetes mellitus secondary to chronic pancreati¬tis / S. Larsen // Dan. Med. Bull. – 1993. – Vol. 40. – P. 153–162.
24. Magruder J. T. Diabetes and pancre¬atic cancer: chicken or egg? / J. T. Magruder, D. Elahi, D. K. Andersen // Pancreas. – 2011. – Vol. 40. – P. 339–351.
25. 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 / D. M. Nathan, J. B. Buse, M. B. Davidson [et al.] // Diabetes Care. – 2009. – Vol. 32. – P. 193–203.
26. Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis / S. Larsen, J. Hilsted, B. Tronier, H. Worning // Metabolism. – 1987. – Vol. 36. – P. 964–967.
27. Metformin use is associated with better survival of dia¬betic patients with pancreatic cancer / N. Sadeghi, J. L. Abbruzzese, S. C. Yeung [et al.] // Clin. Cancer Res. – 2012. – Vol. 18. – P. 2905–2912.
28. Mohan V. Tropical chronic pancreatitis / V. Mohan, C. Pitchumoni // The Pancreas / Eds. H. G. Beger, A. L. Warshaw, M. W. Buechler [et al.]. – London : Blackwell Science, 1998. – P. 688–697.
29. Occurrence of and risk factors for diabetes mellitus in Chinese patients with chronic pancreatitis / W. Wang, Y. Guo, Z. Liao // Pancreas. – 2011. – Vol. 40. – P. 206–212.
30. Olsen T. S. Lipomatosis of the pancreas in autopsy material and its relation to age and overweight / T. S. Olsen // Acta Pathol. Microbiol. Scand. A. – 1978. – Vol. 86A. – P. 367–373.
31. Pancreatic exocrine function in patients with type 1 and type diabetes mellitus / P. D. Hardt, A. Krauss, L. Bretz [et al.] // Acta Diabetol. – 2000. – Vol. 37. – P. 105–110.
32. Pancreatic hor¬mone secretion in chronic pancreatitis without residual beta¬cell function / S. Larsen, J. Hilsted, B. Tronier, H. Worning // Acta Endocrinol (Copenh). – 1988. – Vol. 118. – P. 357–364.
33. Pancreatic polypep¬tide response to secretin in obesity: effects of glucose intolerance / B. Glaser, G. Zoghlin, K. Pienta, A. I. Vinik // Horm. Metab. Res. – 1988. – Vol. 20. – P. 288–292.
34. Pancreatitis and pancreatic cancer risk : a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4) / E. J. Duell, E. Lucenteforte, S. H. Olson [et al.] // Ann. Oncol. – 2012. – Vol. 23. – P. 2964–2970.
35. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group / A. B. Lowenfels, P. Maisonneuve, G. Cavallini [et al.] // N. Engl. J. Med. – 1993. – Vol. 328. – P. 1433–1437.
36. Prevalence and determinants of exocrine pan¬creatic insufficiency among older adults : results of a population-based study / D. Rothenbacher, M. Löw, P. D. Hardt [et al.] // Scand. J. Gastroenterol. – 2005. – Vol. 40. – P. 697–704.
37. Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c) / N. Ewald, C. Kaufmann, A. Raspe [et al.] // Diabetes Metab. Res. Rev. – 2012. – Vol. 28. – P. 338–342.
38. Risk factors for diabetes mellitus in chronic pancreatitis / D. Malka, P. Hammel, A. Sauvanet [et al.] // Gastroen¬terology. – 2000. – Vol. 119. – P. 1324–1332.
39. Role of fat hydrolysis in regulating glucagon-like Peptide-1 secretion / S. Beglinger, J. Drewe, J. Schirra [et al.] // J. Clin. Endocrinol. Metab. – 2010. – Vol. 95. – P. 879–886.
40. Sikkens E. C. The prevalence of fat-soluble vitamin deficiencies and a decreased bone mass in patients with chronic pancreatitis / E. C. Sikkens, D. L. Cahen, A. D. Koch // Pancreatology. – 2013. – Vol. 13. – P. 238–242.
41. The Diabetes Control and Complications Trial (DCCT). Design and methodologic considerations for the feasibility phase. The DCCT Research Group // Diabetes. – 1986. – Vol. 35. – P. 530–545.
42. The natural history of hereditary pancreatitis : a national series / V. Rebours, M. C. Boutron-Ruault, M. Schnee [et al.] // Gut. – 2009. – Vol. 58. – P. 97–103.
43. Tropi¬cal or malnutrition-related diabetes: a real syndrome? / A. Abu-Bakare, R. Taylor, G. V. Gill, K. G. Alberti // Lancet. – 1986. – Vol. 1. – P. 1135–1138.
44. Type 1 diabetes mellitus associated with clinical acute pancreatitis in an adult / T. Moriai, Y. Morita, T. Matsui, M. Okada // Pancreas. – 2000. – Vol. 20. – P. 415–416.
45. UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance // Diabetologia. – 1991. – Vol. 34. – P. 877–890.
46. Valenzuela J. E. Pancreatic polypeptide response in patients with chronic pancreatitis / J. E. Valenzuela, I. L. Taylor, J. H. Walsh // Dig. Dis. Sci. – 1979. – Vol. 24. – P. 862–864.