The Pathogenesis of Diabetes Mellitus *

It was originally maintained by Naunyn that, with very rare exceptions, the underlying cause of diabetes was an inborn biologic inferiori-ty, primarily of the pancreatic reserve. Recently, Joslin27 has written, "Ever increasing evidence points strongly to the validity of the Naunyn conception of the unilty of diabetes with heredity as the common bond." Wilder41 opens his discussion of the pathogenesis with the heading: "The primary cause of diabetes; inadequate insular reserve." Today most authorities accept this unitary pancreatic hypothesis. It is assumed that upon this inherited tendency there must be superimposed factors which at a given time in the individual's life become prominent enough to precipitate the disease. The development of diabetes in the predisposed is due to a variety of causes. In the first place there are hereditary or acquired conditions which reduce the insular reserve. Secondly, there are hereditary or acquired disorders of metabolism which, by creating a greater demand for insulin, impose an added strain on the island cells. As Long30 has said, the sum of all this is that insulin deficiency, either relative or absolute, appears to play the central role in this disease. In order to define the extent to which the generally accepted theory of dia!betes is supported, I shall discuss the inheritance of diabetes and the factors precipitating the disease. It is well to recall that much is still unknown about diabetes, that favorite facts can still be challenged, and that deduction from laboratory experiment has certain limitations. This presentation will, therefore, attempt to draw a picture, which is by no means the final one, of the pathogenesis of this disease. How is the inheritance of an inadequate insulin reserve manifested? In descrilbing this I shall adopt the view that the knowledge of diabetes must be examined for its relation to the theory of inherited inferiority. In addition to the direct evidence that diabetes is inherited, physiology and pathology will be sea-ched for facts having a possible bearing on the relationship of heredity to pancreatic or pituitary dysfunction.