Table of Contents Author Guidelines Submit a Manuscript
Experimental Diabetes Research
Volume 2011, Article ID 761950, 7 pages
http://dx.doi.org/10.1155/2011/761950
Review Article

Exocrine Pancreatic Insufficiency in Diabetes Mellitus: A Complication of Diabetic Neuropathy or a Different Type of Diabetes?

Third Medical Department, University Hospital Giessen and Marburg, Giessen Site, Klinikstraße 33, 35392 Giessen, Germany

Received 27 March 2011; Accepted 25 May 2011

Academic Editor: Stavros Liatis

Copyright © 2011 Philip D. Hardt and Nils Ewald. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. H. M. Pollard, L. Miller, and W. A. Brewer, “External secretion of the pancreas and diabetes (study of secretin test),” The American Journal of Digestive Diseases, vol. 10, no. 1, pp. 20–23, 1943. View at Publisher · View at Google Scholar · View at Scopus
  2. W. Y. Chey, H. Shay, and C. R. Shuman, “External pancreatic secretion in diabetes mellitus,” Annals of Internal Medicine, vol. 59, pp. 812–821, 1963. View at Google Scholar · View at Scopus
  3. J. B. Vacca, W. J. Henke, and W. A. Knight, “The exocrine pancreas in diabetes mellitus,” Annals of Internal Medicine, vol. 61, pp. 242–247, 1964. View at Google Scholar
  4. B. M. Frier, J. H. B. Saunders, K. G. Wormsley, and I. A. D. Bouchier, “Exocrine pancreatic function in juvenile-onset diabetes mellitus,” Gut, vol. 17, no. 9, pp. 685–691, 1976. View at Google Scholar · View at Scopus
  5. P. G. Lankisch, G. Manthey, J. Otto, M. Talaulicar, B. Willms, and W. Creutzfeldt, “Exocrine pancreatic function in insulin-dependent diabetes mellitus,” Digestion, vol. 25, pp. 210–216, 1982. View at Google Scholar
  6. G. Gröger and P. Layer, “Exocrine pancreatic function in diabetes mellitus,” The European Journal of Gastroenterology and Hepatology, vol. 7, pp. 740–746, 1995. View at Google Scholar
  7. W. Gepts, “Pathologic anatomy of the pancreas in juvenile diabetes mellitus,” Diabetes, vol. 14, no. 10, pp. 619–633, 1965. View at Google Scholar · View at Scopus
  8. N. MacLean and R. F. Ogilvie, “Observations on the pancreatic islet tissue of young diabetic subjects,” Diabetes, vol. 8, no. 2, pp. 83–91, 1959. View at Google Scholar · View at Scopus
  9. P. M. Le Compte and W. Gepts, “The pathology of juvenile diabetes,” in The Diabetic Pancreas, B. W. Volk and K. F. Wellmann, Eds., pp. 325–363, Plenum Press, New York, NY, USA, 1977. View at Google Scholar
  10. U. Scheefers-Borchel, H. Scheefers, R. Arnold, P. Fischer, and A. Sziegoleit, “Pankreatische Elastase 1: Parameter für die chronische und akute Pankreatitis,” Laboratoriumsmedizin, vol. 16, no. 12, pp. 427–432, 1992. View at Google Scholar · View at Scopus
  11. A. Sziegoleit, E. Krause, H. U. Klör, L. Kanacher, and D. Linder, “Elastase 1 and chymotrypsin B in pancreatic juice and feces,” Clinical Biochemistry, vol. 22, no. 2, pp. 85–89, 1989. View at Google Scholar · View at Scopus
  12. C. Löser, A. Möllgaard, and U. R. Fölsch, “Faecal elastase 1: a novel, highly sensitive and specific tubeless pancreatic function test,” Gut, vol. 39, no. 4, pp. 580–586, 1996. View at Google Scholar · View at Scopus
  13. J. Stein, Z. Spirchez, B. Lembcke, and W. F. Caspary, “Investigations to the diagnostic value of elastase 1 test,” Zeitschrift fur Gastroenterologie, supplement 1, pp. 122–129, 1997. View at Google Scholar
  14. J. E. Dominguez-Munoz, C. Hieronymus, T. Sauerbruch, and P. Malfertheiner, “Fecal elastase test: evaluation of a new noninvasive pancreatic function test,” The American Journal of Gastroenterology, vol. 90, no. 10, pp. 1834–1837, 1995. View at Google Scholar · View at Scopus
  15. P. D. Hardt, A. Krauss, L. Bretz et al., “Pancreatic exocrine function in patients with type-1 and type-2 diabetes mellitus,” Acta Diabetologica, vol. 37, no. 3, pp. 105–110, 2000. View at Publisher · View at Google Scholar · View at Scopus
  16. P. D. Hardt, A. Hauenschild, J. Nalop et al., “High prevalence of exocrine pancreatic insufficiency in diabetes mellitus. A multicenter study screening fecal elastase 1 concentrations in 1,021 diabetic patients,” Pancreatology, vol. 3, no. 5, pp. 395–402, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. W. Rathmann, B. Haastert, A. Icks et al., “Low fecal elastase 1 concentrations in type 2 diabetes,” Scandinavian Journal of Gastroenterology, vol. 36, pp. 1056–1061, 2001. View at Google Scholar
  18. A. Icks, B. Haastert, G. Giani, and W. Rathmann, “Low fecal elastase-1 in type I diabetes mellitus,” Zeitschrift fur Gastroenterologie, vol. 39, no. 10, pp. 823–830, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. F. Cavalot, K. Bonomo, P. Perna et al., “Pancreatic elastase-1 in stools, a marker of exocrine pancreas function, correlates with both residual β-cell secretion and metabolic control in type 1 diabetic subjects,” Diabetes Care, vol. 27, no. 8, pp. 2052–2054, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Harano, C. I. Kim, M. Kang et al., “External pancreatic dysfunction associated with diabetes mellitus,” Journal of Laboratory and Clinical Medicine, vol. 91, pp. 780–790, 1978. View at Google Scholar
  21. G. Bretzke, “Diabetes mellitus und exokrine Pankreas funktion,” Zeitschrift fur die Gesamte Innere Medizin und Ihre Grenzgebiete, vol. 39, no. 16, pp. 388–390, 1984. View at Google Scholar
  22. H. El Newihi, C. P. Dooley, C. Saad, J. Staples, A. Zeidler, and J. E. Valenzuela, “Impaired exocrine pancreatic function in diabetics with diarrhea and peripheral neuropathy,” Digestive Diseases and Sciences, vol. 33, no. 6, pp. 705–710, 1988. View at Google Scholar
  23. P. D. Hardt and H. U. Kloer, “Diabetes mellitus and exocrine pancreatic disease,” in Pancreatic Disease, C. D. Johnson and C. W. Imrie, Eds., pp. 235–241, Springer, London, UK, 2nd edition, 1998. View at Google Scholar
  24. A. C. Nunes, J. M. Pontes, A. Rosa, L. Gomes, M. Carvalheiro, and D. Freitas, “Screening for pancreatic exocrine insufficiency in patients with diabetes mellitus,” The American Journal of Gastroenterology, vol. 98, no. 12, pp. 2672–2675, 2003. View at Publisher · View at Google Scholar · View at PubMed
  25. A. Yilmaztepe, E. Ulukaya, C. Ersoy, M. Yilmaz, and H. A. Tokullugil, “Investigation of fecal pancreatic elastase-1 levels in type 2 diabetic patients,” The Turkish Journal of Gastroenterology, vol. 16, no. 2, pp. 75–80, 2005. View at Google Scholar
  26. P. D. Hardt, A. Hauenschild, C. Jaeger, J. Teichmann, R. G. Bretzel, and H. U. Kloer, “High prevalence of steatorrhea in 101 diabetic patients likely to suffer from exocrine pancreatic insufficiency according to low fecal elastase 1 concentrations a prospective multicenter study,” Digestive Diseases and Sciences, vol. 48, no. 9, pp. 1688–1692, 2003. View at Publisher · View at Google Scholar
  27. F. Cavalot, K. Bonomo, E. Fiora et al., “Does pancreatic elastase-1 in stools predict steatorrhea in type 1 diabetes?” Diabetes Care, vol. 29, no. 3, pp. 719–721, 2006. View at Google Scholar
  28. W. Creutzfeldt, D. Gleichmann, J. Otto, F. Stöckmann, P. Maisonneuve, and P. G. Lankisch, “Follow-up of exocrine pancreatic function in type-1 diabetes mellitus,” Digestion, vol. 72, no. 2-3, pp. 71–75, 2005. View at Publisher · View at Google Scholar · View at PubMed
  29. R. Ebert and W. Creutzfeldt, “Reversal of impaired GIP and insulin secretion in patients with pancreatogenic steatorrhea following enzyme substitution,” Diabetologia, vol. 19, no. 3, pp. 198–204, 1980. View at Google Scholar
  30. C. Herrmann, R. Göke, H. C. Fehmann, G. Richter, R. Arnold, and B. Göke, “Glucagon-like peptide 1 and glucose-dependent insulin-releasing polypeptide secretion in response to nutrients,” Digestion, vol. 56, no. 2, pp. 117–126, 1995. View at Google Scholar
  31. H. T. Blumenthal, J. G. Probstein, and A. W. Berns, “Interrelationship of diabetes mellitus and pancreatitis,” Archives of Surgery, vol. 87, pp. 844–850, 1963. View at Google Scholar
  32. R. S. Olsen, “The incidence and clinical relevance of chronic inflammation in the pancreas in autopsy material,” Acta Pathologica et Microbiologica Scandinavica—Section A, vol. 86, no. 5, pp. 361–364, 1978. View at Google Scholar
  33. A. K. Foulis and J. A. Stewart, “The pancreas in recent-onset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue,” Diabetologia, vol. 26, no. 6, pp. 456–461, 1984. View at Google Scholar
  34. J. Rahier, R. M. Goebbels, and J. C. Henquin, “Cellular composition of the human diabetic pancreas,” Diabetologia, vol. 24, no. 5, pp. 366–371, 1983. View at Google Scholar
  35. K. Nakanishi, T. Kobayashi, H. Miyashita et al., “Exocrine pancreatic ductograms in insulin-dependent diabetes mellitus,” The American Journal of Gastroenterology, vol. 89, no. 5, pp. 762–766, 1994. View at Google Scholar
  36. P. D. Hardt, A. Killinger, J. Nalop, H. Schnell-Kretschmer, T. Zekorn, and H. U. Klör, “Chronic pancreatitis and diabetes mellitus. A retrospective analysis of 156 ERCP investigations in patients with insulin-dependent and non-insulin-dependent diabetes mellitus,” Pancreatology, vol. 2, no. 1, pp. 30–32, 2002. View at Publisher · View at Google Scholar
  37. F. Chiarelli, A. Verrotti, E. Altobelli, A. Blasetti, and G. Morgese, “Size of the pancreas in type I diabetic children and adolescents,” Diabetes Care, vol. 18, no. 11, pp. 1505–1506, 1995. View at Google Scholar
  38. V. Fonseca, L. A. Berger, A. G. Beckett, and P. Dandona, “Size of pancreas in diabetes mellitus: a study based on ultrasound,” The British Medical Journal—Clinical Research, vol. 291, no. 6504, pp. 1240–1241, 1985. View at Google Scholar
  39. J. P. Gilbeau, V. Poncelet, E. Libon, G. Derue, and F. R. Heller, “The density, contour and thickness of the pancreas in diabetics,” The American Journal of Roentgenology, vol. 159, no. 3, pp. 527–531, 1992. View at Google Scholar
  40. M. Bilgin, N. C. Balci, A. J. Momtahen, Y. Bilgin, H. U. Klör, and W. S. Rau, “MRI and MRCP findings of the pancreas in patients with diabetes mellitus: compared analysis with pancreatic exocrine function determined by fecal elastase 1,” Journal of Clinical Gastroenterology, vol. 43, no. 2, pp. 165–170, 2009. View at Publisher · View at Google Scholar · View at PubMed
  41. J. A. Williams and I. D. Goldfine, “The insulin-pancreatic acinar axis,” Diabetes, vol. 34, no. 10, pp. 980–986, 1985. View at Google Scholar
  42. G. Adler and H. F. Kern, “Regulation of exocrine pancreatic secretory process by insulin,” Hormone and Metabolic Research, vol. 7, no. 4, pp. 290–296, 1975. View at Google Scholar
  43. M. Korc, D. Owerbach, C. Quinto, and W. J. Rutter, “Pancreatic islet-acinar cell interaction: amylase messenger RNA levels are determined by insulin,” Science, vol. 213, no. 4505, pp. 351–353, 1981. View at Google Scholar
  44. M. Löhr and G. Klöppel, “Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type i (insulin dependent) diabetes mellitus and microangiopathy,” Diabetologia, vol. 30, no. 10, pp. 757–762, 1987. View at Google Scholar
  45. J. R. Henderson, “Why are the islets of Langerhans?” The Lancet, vol. 2, no. 7618, pp. 469–470, 1969. View at Google Scholar
  46. R. H. Unger, E. Aguilar-Parada, W. A. Müller, and A. M. Eisentraut, “Studies of pancreatic alpha cell function in normal and diabetic subjects,” The Journal of Clinical Investigation, vol. 49, no. 4, pp. 837–848, 1970. View at Google Scholar
  47. W. P. Dyck, J. Rudick, B. Hoexter, and H. D. Janowitz, “Influence of glucagon on pancreatic exocrine secretion,” Gastroenterology, vol. 56, no. 3, pp. 531–537, 1969. View at Google Scholar
  48. K. Gyr, C. Beglinger, E. Kohler, U. Trautzl, U. Keller, and S. R. Bloom, “Circulating somatostatin. Physiological regulator of pancreatic function?” The Journal of Clinical Investigation, vol. 79, pp. 1595–1600, 1987. View at Google Scholar
  49. J. Y. Patel and G. C. Weir, “Increased somatostatin content of islets from streptozotocin-diabetic rats,” Clinical Endocrinology, vol. 5, no. 2, pp. 191–194, 1976. View at Google Scholar
  50. S. Tanaka, T. Kobayashi, K. Nakanishi et al., “Corticosteroid-responsive diabetes mellitus associated with autoimmune pancreatitis: pathological examinations of the endocrine and exocrine pancreas,” Annals of the New York Academy of Sciences, vol. 958, pp. 152–159, 2002. View at Google Scholar
  51. G. Klöppel, J. Lüttges, M. Löhr, G. Zamboni, and D. Longnecker, “Autoimmune pancreatitis: pathological, clinical and immunological features,” Pancreas, vol. 27, no. 1, pp. 14–19, 2003. View at Publisher · View at Google Scholar
  52. T. Kobayashi, K. Nakanishi, H. Kajio et al., “Pancreatic cytokeratin: an antigen of pancreatic exocrine cell autoantibodies in type 1 (insulin-dependent) diabetes mellitus,” Diabetologia, vol. 33, no. 6, pp. 363–370, 1990. View at Publisher · View at Google Scholar
  53. L. Panicot, E. Mas, C. Thivolet, and D. Lombardo, “Circulating antibodies against an exocrine pancreatic enzyme in type 1 diabetes,” Diabetes, vol. 48, no. 12, pp. 2316–2323, 1999. View at Google Scholar
  54. A. Imagawa, T. Hanafusa, J. I. Miyagawa, and Y. Matsuzawa, “A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies,” The New England Journal of Medicine, vol. 342, no. 5, pp. 301–307, 2000. View at Publisher · View at Google Scholar · View at PubMed
  55. T. Taniguchi, K. Okazaki, M. Okamoto et al., “High prevalence of autoantibodies against carbonic anhydrase II and lactoferrin in type 1 diabetes: concept of autoimmune exocrinopathy and endocrinopathy of the pancreas,” Pancreas, vol. 27, no. 1, pp. 26–30, 2003. View at Publisher · View at Google Scholar
  56. O. Günther, Zur Ätiologie des Diabetes Mellitus, Akademie-Verlag, Berlin, Germany, 1961.
  57. K. G. M. M. Alberti, “Diabetes secondary to pancreatopathy: an example of brittle diabetes,” in Diabetes Secondary to Pancreatopathy. International Congress Series 762, A. Tiengo, K. G. M. M. Alberti, S. DelPrato, and M. Vranic, Eds., pp. 7–20, Excerpta Medica, Amsterdam, The Netherlands, 1988. View at Google Scholar
  58. P. D. Hardt, M. D. Brendel, H. U. Kloer, and R. G. Bretzel, “Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed?” Diabetes Care, vol. 31, pp. S165–S169, 2008. View at Google Scholar
  59. J. Pirart, “Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973,” Diabetes Care, vol. 1, no. 4, pp. 252–263, 1978. View at Google Scholar
  60. F. Strian and M. Halsbeck, “Neurologische Erkrankungen,” in Diabetologie in Klinik und Praxis, H. Mehnert, E. Standl, K. H. Usadel, and H. U. Häring, Eds., pp. 802–805, Thieme, Stuttgart, Germany, 2003. View at Google Scholar
  61. N. Ewald, A. Raspe, C. Kaufmann, R. G. Bretzel, H. U. Kloer, and P. D. Hardt, “Determinants of exocrine pancreatic function as measured by fecal elastase-1 concentrations (FEC) in patients with diabetes mellitus,” The European Journal of Medical Research, vol. 14, no. 3, pp. 118–122, 2009. View at Google Scholar
  62. M. Vesterhus, H. Ræder, H. Aurlien et al., “Neurological features and enzyme therapy in patients with endocrine and exocrine pancreas dysfunction due to CEL mutations,” Diabetes Care, vol. 31, no. 9, pp. 1738–1740, 2008. View at Publisher · View at Google Scholar · View at PubMed
  63. G. Davidai, T. Zakaria, R. Goldstein, A. Gilai, and S. Freier, “Hypovitaminosis E induced neuropathy in exocrine pancreatic failure,” Archives of Disease in Childhood, vol. 61, pp. 901–903, 1986. View at Google Scholar