photo-creutzfeldt2The field of gastrointestinal Endocrinology has gained widespread attention over the last decades, as the importance of gut hormones in the regulation of glucose homeostasis, gastrointestinal functions and energy homeostasis has now become more and more evident. One of the fathers of this concept was Professor Werner Creutzfeldt, whose landmark research contributions pioneered this field for the past 50 years. His foresighted research activities have led to the detailed investigation of the incretin effect, i.e. the augmentation of insulin secretion by gut hormones, which has now been accepted as a key mechanism for postprandial glucose control. On August 30th, 2006, Werner Creutzfeldt passed away after a long and heroic struggle against a series of chronic illnesses. Perhaps as a small solace, he could see the emerging fruits of his long-standing and visionary research one year prior to his death, when the first member of the new drug class of incretin mimetics was launched for the treatment of type 2 diabetes, which for certain would not have been available at this time without the invaluable contributions made by him personally and the Goettingen research group.

Werner Creutzfeldt was born on May 11th, 1924 in Kiel,Germany, and attended Medical School at the Universities of Freiburg, Kiel, and Tübingen. In his early research projects – carried out at the University of Freiburg where he worked as a resident and later as a senior consultant – he provided a detailed description of the morphology and function of the islets of Langerhans and their abnormalities in various experimental models of diabetes. These studies still impress with their detailedness, accuracy and innovative methodology. In subsequent research projects, Werner Creutzfeldt examined the morphological and biochemical features of neuroendocrine tumours, the pharmacokinetics and pharmacodynamics of oral antidiabetic agents and the pathophysiology of “post-transfusion” hepatitis. These contributions soon became classic landmarks in the field. In 1964, Werner Creutzfeldt was appointed full professor and chairman of the Department of Medicine at the University of Göttingen, where he soon formed one of the most recognized groups in the fields of Gastroenterology and Endocrinology, from which numerous highly successful scientists emerged, many of which have subsequently taken over leading academic positions in Internal Medicine themselves.

Werner Creutzfeldt served in many national and international positions, including as President of the European Association for the Study of Diabetes (1971–1974), President of the European Pancreatic Club (1969), President of the German Diabetes Association (1967–1968), and President of the German Association for Gastroenterology (1976–1977). He was also Editor-in-Chief of the journals “Diabetologia” (1973–1976) and “Digestion” (1978–1992).

During his most impressive career, Werner Creutzfeldt has received many honours including the Claude-Bernard-Medal of the European Association for the Study of Diabetes, the Ludwig-Heilmeyer-Medal of the German Association for Internal Medicine, the Paul-Langerhans-Medal of the German Diabetes Association, the Ismar-Boas-Medal and the Thannhauser-Medal of the German Gastroenterological Society and the most prestigious Ernst-Jung-Medal for Medicine in Gold of the Hamburg Ernst-Jung-Foundation.

With more than 700 published original articles, reviews and book chapters, Werner Creutzfeldt’s scientific merits are too numerous to be described in detail. Perhaps the most important contributions made by the Göttingen research group directed and inspired by him include the characterisation of Gastric Inhibitory Polypeptide (GIP) in the physiology of postprandial glucose homeostasis, the uncovering of defects in the entero-insular axis in the pathophysiology of type 2 diabetes and the first description of the biological activity and antidiabetic effects of glucagon-like peptide-1 (GLP-1). In many ways, the development of dipeptidyl peptidase-4 (DPP-4) inhibitors and incretin mimetics as a novel concept in the pharmacotherapy of type 2 diabetes would be unthinkable without his fundamental contributions to the field.

Werner Creutzfeldt’s broad range of interests not only covered several aspects of Gastroenterology and Endocrinology, but also questions of ethics in Medicine, the brutal abuse and misconduct of medical research by the nazi-regime in Germany, as well as the history of diabetes and gastrointestinal research. Having experienced the crimes of the nazi-regime as a young man (his mother was imprisoned by the nazis during the war), he actively fought against antisemitism and the discrimination of minorities throughout his life. As chairman of the Ethics Committee of the Medical Faculty of the University of Göttingen, he was a thoughtful and critical defender of the boundaries for medical research in human subjects.

It was Werner Creutzfeldt’s vision that Gastroenterology, Endocrinology and Diabetology/Metabolism are one inseparable unit that should not be sub-divided into separate entities. He was one of the first scientists to realize the clinical importance of the gut as an endocrine organ and to uncover the close interaction between gastrointestinal motility, secretion and the regulation of energy balance. Today, his foresighted visions and ideas have become accepted doctrines in Internal Medicine, and his fundamental studies have paved the way towards new principles in our understanding of the pathophysiology and treatment of various diseases. Beside his research activities Werner Creutzfeldt was a brilliant physician who personally cared for his patients. His grand rounds on the ward were exceptional examples for his sophisticated clinical skills, his sharp intellect and his ability to dissect and analyse the clinical picture of a patient. One of this outstanding clinical lecture series was “Differential diagnosis in internal medicine” where he demonstrated that the physician should be able to deduce a diagnosis just from the patient’s history and examination. This demonstration of the “Art of Medicine” excited his medical students who regularly overcrowded his lecture halls.

Wolfgang E. Schmidt
Juris J. Meier
(Excerpt from Regulatory Peptides, 137, 2006, 105-106)