Follow-up of exocrine pancreatic function in type-1 diabetes mellitus.

In a previous study, mild to moderate exocrine pancreatic insufficiency, as measured by the secretin-pancreozymin test, was found in 23 (43%) of 53 patients with type-1 diabetes mellitus. Of these 53 patients, 20 (7 of whom initially had an abnormal secretin-pancreozymin test) were available for a follow-up examination 11 years later. Of the 7 patients with abnormal exocrine pancreatic function at the first test, 5 remained abnormal and 2 became normal, whereas of the 13 patients with initially normal pancreatic function the test result remained normal in 11 patients and became abnormal in 2. In these 2 groups the test result did not differ significantly between both tests. However, exocrine pancreatic function had returned to normal or had become abnormal in 2 patients, respectively, at the second test. In the 3 patients with exocrine pancreatic insufficiency at the first and second tests, the lipase level had not fallen below 10% or less than the normal level at which steatorrhea occurs and therapy is required. There was no significant correlation between the duration of the diabetes and the test results for both time points of investigation. The data suggest that mild to moderate exocrine pancreatic insufficiency found in type-1 diabetes is due to an early event in the course of the diabetes and does not progress. Therefore, this finding is of minor clinical importance and expensive pancreatic enzyme substitution will not be required.

History of the European pancreatic club: the first 40 years 1965-2005. The development of the European pancreatic club as a scientific society.

The European Pancreatic Club (EPC) was founded during a first symposium on December 9 and 10, 1965 in London (President H.T. Howat). The nine founding members were one biochemist (Jean Christophe, Belgium), one physiologist (Alfred A. Harper, UK), two surgeons (André Delcourt, Belgium, Yngve Edlund, Norway) and five physicians with special interest in the pancreas (Werner Creutzfeldt, Germany, Oliver Fitzgerald, Ireland, Karel Herfort, Czechoslovakia, Henry T. Howat, UK, Henri Sarles, France). It was the first scientific society worldwide which was concerned with the study of the pancreas. The idea was to bring basic scientists and clinicians together in an informal atmosphere to promote friendship and communication on research between them. The 2nd symposium was held in Marseilles in 1967 (President H. Sarles). Until now there have nearly always been annual meetings, the one in 2005 is the 37th. In 1973 the EPC decided to lay down 'Internal Rules' and in 1992 new statutes were introduced. It became a member of the United European Gastroenterology Federation (UEGF) and is coorganizer of the United European Gastroenterology Week (UEGW). The official journal has been Pancreatology since 2001; previously the abstracts had been printed in Digestion since 1982. The officers of the EPC are the President, the Past President, the President Elect, the Secretary, the Treasurer and six Councillors from different European countries, three from basic and three from clinical science. A selection committee (4 basic and 4 clinical scientists) decides on the acceptance of papers. Officers and Presidents are elected by the General Assembly. At the meetings on average 150 contributions are accepted for presentation; the abstracts are printed in Pancreatology. Papers came from nearly all European countries and from overseas. In numbers Germany, France, the UK, Italy and Sweden are at the top. In total 4,837 scientific presentations were made from 1971 to 2004. Fifty-nine symposia and 245 invited lectures informed about the state of the art. Since 1991 a Young Researchers Corner given by international experts is especially designed to give information on new techniques of research. The European Study Group of Pancreatic Cancer (ESPAC) and the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) are affiliated with the EPC. Since 1999 a Newsletter of the EPC has been published. The website of the EPC is www.e-p-c.org.

History of the European pancreatic club: the first 40 years 1965-2005. The scientific profile of the European pancreatic club and what stood the test of time.

The invited lectures, the symposia and panels and the printed abstracts of the meetings are the basis for analysis of the development of pancreatic research over the 40 years from 1965 to 2005. 245 invited lectures and 59 symposia, panels and round tables presented and discussed the latest state of the art at the meetings of the European Pancreatic Club (EPC). We analyze in detail the contributions to physiology and biochemistry of the pancreas, the neurohormonal control of pancreatic secretion, cell biology, stimulus-secretion coupling, and cell receptors. The research on the endocrine-exocrine relationship, nutrition and the pancreas, experimental and clinical acute and chronic pancreatitis, function tests and imaging of the pancreas, pancreatic development and growth, experimental and clinical pancreatic carcinoma, genetics and inherited pancreatic diseases over the years are listed in special sections and discussed. At the center of the EPC meetings there are scientific sessions with either oral or poster presentations. From 1971 to 2004, 4,837 contributions were accepted and printed as abstracts. In the first 30 years papers on basic research usually amounted to around 30-40%, on pathophysiology also 20-40% and the rest were on clinical work. In the years since 1993 the basic contributions became less with 20% and even only 10% of all papers in the last years. Abstracts from pathophysiology and pathology increased in the 1990s, mainly with work on pancreatic carcinoma. Papers on clinical topics also rose to 40-50% of all in the years since 1998. The interest in clinical topics shifted over the years. Chronic pancreatitis was the main topic in the 1970s; in the 1980s until 2000, acute pancreatitis gained more interest, and pancreatic cancer is now an attractive field of study due to new methods of research with cancer cell lines and genetic models. Since 1993 a Young Researchers Corner with international experts is offered at the meetings of the EPC, the programs are analyzed. In the last section the question of 'what stood the test of time?' is asked as reflected in 40 years of meetings of the EPC. Topics are physiology, biochemistry and cell biology in relation to the pancreas, pathogenesis of acute and chronic pancreatitis, methods of diagnosis, treatment of pancreatitis and of carcinoma.

The [pre-] history of the incretin concept.

The discoverers of secretin already thought of the existence of a chemical excitant for the internal secretion of the pancreas. Numerous experiments have been performed and published between 1906 and 1935 testing the effect of injected or ingested duodenal ("secretin") extracts on fasting or elevated blood glucose levels of normal or diabetic animals and humans with contradictory results. In 1940, after a series of negative dog experiments performed by an opinion leader, the existence of an incretin was considered questionable and further research stopped for more than 20 years. However, after the development of the radio-immunoassay, the incretin-concept has been revived in 1964, showing that significantly more insulin was released after ingestion of glucose than after intravenous injection. The possibility that nerves or one of the known gut hormones were responsible for the incretin effect could be ruled out. In 1970, glucose dependent insulinotropic polypeptide (GIP), and finally, in 1985 glucagon-like peptide 1 (GLP-1) and its truncated form GLP-1(7-36) were recognized as true incretins. Thereafter, multiple antidiabetic qualities and the therapeutic perspectives of GLP-1(7-36) and its analogues and mimetics have been demonstratred.

Incretins and their analogues as new antidiabetic drugs.

Glucagon-like peptide 1 (GLP-1) is a gut (incretin) hormone with multiple actions that could potentially contribute to an antidiabetic effect. This includes: (a) glucose-dependent insulinotropic actions; (b) glucagonostatic actions; (c) a reduction in appetite/promotion of satiety leading to reduced food intake and weight reduction; (d) the deceleration of gastric emptying; and (e) the stimulation of islet growth, differentiation and regeneration. Thus, multiple aspects of the type 2 diabetic phenotype can potentially be improved or even corrected by GLP-1. The native gut hormone, however, after intravenous injection or absorption from subcutaneous depots, is proteolytically degraded and eliminated from the circulation too quickly to be useful for the treatment of diabetes. GLP-1 derivatives (receptor agonists) with prolonged pharmacokinetics that promise a potential for clinical use in the near future are being developed.