The pancreatic islets in diabetes.

Despite the fact that heterogeneity of diabetes in man has become more and more evident in recent years, its pancreatic pathology is still represented by two distinct entities, roughly corresponding to the classic juvenile-onset and maturity-onset types of the disease. In juvenile-onset, insulin-dependent diabetes, the pancreatic islets show severe and pathognomonic changes. B cells are greatly reduced in number already at clinical onset. Contrary to classic opinion they do not always disappear in the years to follow. Insulitis, a common finding in the pancreas of recent onset juvenile diabetic subjects, is compatible with a viral infection as well as with an autoimmune reaction as the cause of B cell destruction. In the pancreas of juvenile-onset diabetic subjects the islets, which in the past have been regarded as atrophic and inactive, are actually composed of cells containing glucagon and somatostatin. There is also a profound distortion of islet organization, and many endocrine cells are scattered as single cells in the exocrine tissue. These findings may well account for the abnormal secretory behavior of the glucagon-secreting A cells in insulin-dependent juvenile-onset diabetes. In maturity-onset, noninsulin-dependent diabetes, the pancreatic pathology is extremely variable and not pathognomonic. A numeric reduction of the B cells can be demonstrated in many maturity-onset diabetic subjects, but this reduction is much more moderate than in insulin-dependent juvenile-onset diabetic subjects and does not account for the disease. The same amount of B cell reduction can be found in many elderly subjects without clinical evidence of diabetes. In many maturity-onset diabetic subjects, the cytologic characteristics of the B cells suggest a decreased responsiveness to the stimulus of hyperglycemia. Islet fibrosis and hyalinosis (amyloidosis), although common, cannot explain this secretory dysfunction. The exact site of the defect in the B cells of maturity-onset diabetic subjects remains to be defined. Further investigations are necessary to assess the role of disturbed intraislet intercellular relationships in the pathogenesis of late-onset diabetes. The dual pattern of islet pathology in diabetes in man does not preclude a more profound heterogeneity in the etiology and pathogenesis of the disease.