Textbook of Diabetes I. [antikvár]

Foreword The diabetic state commands more attention now than ever before. At a time when in all branches of medicine, indeed in all branches of science, the engagement generally with the problem becomes increasingly demanding and technologically complex, understanding diabetes occupies a con-tinuingly prominent place. Diabetes has always stood out in the history of medicine and science. The graphic descriptions by ancient observers must put the severe, insulin-deficient diabetic state among the earliest of the readily recognized clinical conditions, the paradigm of the 'clinical syndrome'. Exploration of the nature of diabetes claimed the attention of the father of experimental medicine, the great Claude Bernard, so much of whose thought and perception remains with us today. He understood the importance of the balance between glucose production and glucose consumption in determining the level of glucose concenh-ation though he had little conception of the factors which regulated them. He saw diabetes essentially as the outcome of a disturbance of relationships, a distortion of a homeostatic system, a disorder of adaptation. Bernard shared the scientific stage with the other giant of 19th century biomedical science, Louis Pasteur, whose discoveries promoted a quite different model of disease, one that was more direct and simple. The disease process resulted from a single, well-defined causal agency — a germ. If the germ was not present, the disease could not occur, though having the germ did not guarantee the appearance of the disease. The Pasteurian notion of disease in the present day context can be extended to include the abnormal gene or a toxic substance as the causal agency of disease. Had Pasteur ever pronounced upon diabetes, he might well have wondered about some specific enzymatic abnormality in the pathways of glucose metabolism, an area not unfamiliar to him. In the contemporary world of diabetes, the Bernardian and the Pasteurian views contend. A pure Bernardian would regard the diabetic state as a disorder of adaptation, a breakdown in the interrelation and regulation of the balance of factors determining glucose production and disposal. It is perhaps best exemplified in the debates in the 1990s by the Reaven concept of glucose intolerance and non-insulin-dependent diabetes mellitus (NIDDM). His construct of the conditions resulting in the diabetic state introduces the interaction of regulatory mechanisms unknown in their nature to Bernard and Pasteur. This construct is compatible with the observed 'continuous distribution' of glucose tolerance/intolerance in most populations, showing no clear break between the normal and the abnormal. The scientific advances of recent decades might seem to promote the Pasteurian view of the diabetic state. We have witnessed an explosive expansion of knowledge and understanding of the genetic control of cell sh-uctiire and function, and its role in the causation of disease. The search for a diabetes (susceptibility) gene has exdted much research interest and is best established in the insulin-dependent variety of diabetes. An environmental trigger which initiates a process culnunating in the destruction of the pancreatic B cell is also sought and fulfils the Pasteurian expectation of a single causal factor of major effect operating in a genetically susceptible setting. It becomes likely that these two major views of the causation of the diabetic state are not mutually incompatible and indeed both operate to explain the occurrence of diabetes in man. Thus, genetic XVll