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.

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.

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 [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.

A 25-year follow-up study of glucose tolerance in first-degree relatives of type 2 diabetic patients: association of impaired or diabetic glucose tolerance with other components of the metabolic syndrome.

A follow-up study of first-degree relatives of type 2 diabetic patients presented the opportunity to study the association of components of the metabolic syndrome with oral glucose tolerance in these subjects. In 1992, 25 years after the first analysis of the cohort, we performed 75-g oral glucose tolerance tests and measured anthropometric data (body mass index, waist-hip ratio), insulin and C-peptide concentrations, and parameters of lipoprotein metabolism (free fatty acids, triglycerides, cholesterol, HDL cholesterol). Of 135 participants, 71 had normal glucose tolerance (GT), 22 had impaired GT, and 42 had diabetic GT (WHO 1985 criteria).

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 rise of gastrointestinal endocrinology since 1970 and Jens F. Rehfeld and his group right in the middle of it.

The scientific achievements of Jens F. Rehfeld, and the impact of the contributions of Jens Rehfeld and his coworkers on our knowledge of gut-brain peptides is reviewed, based on almost 30 years of scientific contact and friendship. The identification of the first gut peptides led to the "immunologic era" and subsequently to the "genetic" era, during which cascades of new knowledge have been generated.

The entero-insular axis in type 2 diabetes--incretins as therapeutic agents.

The search for intestinal factors regulating the endocrine secretion of the pancreas started soon after the discovery of secretin, i.e. nearly 100 years ago.

[Chiral switch, a successful way for developing drugs: example of esomeprazole].

About 25% of common drugs are racemates, i.e. mixtures of their optical or spatial isomers (stereoisomers or enantiomers).

Effects of the alpha-glucosidase inhibitor acarbose on the development of long-term complications in diabetic animals: pathophysiological and therapeutic implications.

Short-term studies with acarbose have demonstrated its efficacy in reducing postprandial blood glucose levels and glycated haemoglobin (HbA(1c)) levels. These effects would be expected to translate into improvements in long-term complications of diabetes, but such data are not yet available due to the long follow-up times required. Animal models of diabetes have, however, demonstrated the efficacy of acarbose in combating the long-term complications of the disease.

[Consensus conferences and guidelines in gastroenterology: an illusion].

Evidence-based medicine describes the present-day situation of a rational medicine which has its origins in the 19th century. At present evidence-based medicine is an ideal which is unattainable due to inadequate data from randomised controlled studies. Guidelines and consensus conferences which are not based on clearcut scientific data from controlled prospective and randomised studies fail to meet the requirements of evidence-based medicine and so cannot improve patient management.

Role of circulating gastrin in colorectal adenomas and carcinomas.

Background/aims: A trophic role of gastrin has been convincingly demonstrated in the oxyntic mucosa of the stomach, but is still a matter of debate in the lower gastrointestinal tract.

Methods: In order to examine the role of circulating gastrin in colorectal adenoma and carcinoma fasting serum gastrin concentrations were determined in 351 patients undergoing complete colonoscopy.

Results: In comparison to controls (n = 145) more patients with either polyps (n = 125) or colorectal carcinoma (n = 81) have slightly increased serum gastrin concentrations, leading to an increased mean, but no change in median serum gastrin levels.

Overnight GLP-1 normalizes fasting but not daytime plasma glucose levels in NIDDM patients.

GLP-1 (7-36 amide) normalizes fasting plasma glucose in NIDDM patients. It was the aim to study the effect of overnight intravenous GLP-1 (7-36 amide) on the following 24 h-glucose profiles. Ten NIDDM patients (7 female, 3 male; age 62 +/- 4 y.

Electron-microscopical evidence for heterogeneity of micronodular argyrophil cell growth in man.

Hypergastrinaemia-associated changes of non-antral argyrophil cells in man are of increasing interest, because of the development of potent inhibitors of gastric acid secretion. Using an antibody against chromogranin A, we identified micronodular endocrine cell hyperplasia of the oxyntic mucosa in gastric biopsy specimens of patients with hypergastrinaemia of different backgrounds. Consecutive ultrathin sections were examined at the electron-microscopical level.

A hyperinsulinaemic, sequentially eu- and hypoglycaemic clamp test to characterize autonomous insulin secretion in patients with insulinoma.

To better characterize autonomous insulin secretory behaviour in insulinoma patients and to establish diagnostic criteria with high accuracy, hyper-insulinaemic, sequentially eu- and hypoglycaemic clamp tests were performed in insulinoma patients and control subjects. Ten patients with insulinoma (benign in nine, histologically proven in nine) and 10 patients with suspected episodes of hypoglycaemia, in whom thorough clinical evaluation excluded an insulinoma, were examined. Five insulinoma patients were restudied after successful extirpation of the tumour.

Early ERCP and papillotomy compared with conservative treatment for acute biliary pancreatitis. The German Study Group on Acute Biliary Pancreatitis.

Background: The role of early endoscopic retrograde cholangiopancreatography (ERCP) and papillotomy in the treatment of patients who have acute biliary pancreatitis without obstructive jaundice is uncertain.

Methods: We conducted a prospective, multicenter study in which 126 patients were randomly assigned to early ERCP (within 72 hours after the onset of symptoms) and endoscopic papillotomy for the removal of stones in the common bile duct, when appropriate, and 112 patients were assigned to conservative treatment. In the conservative-treatment group, ERCP was performed within three weeks if signs of biliary obstruction or sepsis developed.

Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM.

Intravenous glucagon-like peptide (GLP)-1 [7-36 amide] can normalize plasma glucose in non-insulin-dependent diabetic (NIDDM) patients. Since this is no form for routine therapeutic administration, effects of subcutaneous GLP-1 at a high dose (1.5 nmol/kg body weight) were examined.