Gepts W, Lecompte P M
Am J Med. 1981 Jan;70(1):105-15. doi: 10.1016/0002-9343(81)90417-4.
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.
尽管近年来人类糖尿病的异质性越来越明显，但其胰腺病理仍表现为两种不同的类型，大致对应于经典的青少年发病型和成年发病型糖尿病。在青少年发病的胰岛素依赖型糖尿病中，胰岛呈现出严重且具有诊断意义的变化。在临床发病时，B细胞数量就已大幅减少。与传统观点相反，在随后的几年里它们并不总是消失。胰岛炎是近期发病的青少年糖尿病患者胰腺中的常见表现，它与病毒感染以及自身免疫反应导致B细胞破坏均相符。在青少年发病的糖尿病患者的胰腺中，过去被认为萎缩且无活性的胰岛，实际上是由含有胰高血糖素和生长抑素的细胞组成。胰岛组织也存在严重变形，许多内分泌细胞作为单个细胞散在于外分泌组织中。这些发现很可能解释了胰岛素依赖型青少年发病糖尿病中分泌胰高血糖素的A细胞的异常分泌行为。在成年发病的非胰岛素依赖型糖尿病中，胰腺病理变化极大且无诊断特异性。在许多成年发病的糖尿病患者中可证实B细胞数量减少，但这种减少比胰岛素依赖型青少年发病糖尿病患者更为缓和，且不能解释该疾病。在许多无糖尿病临床证据的老年人中也能发现相同程度的B细胞减少。在许多成年发病的糖尿病患者中，B细胞的细胞学特征表明其对高血糖刺激的反应性降低。胰岛纤维化和透明变性（淀粉样变性）虽然常见，但无法解释这种分泌功能障碍。成年发病糖尿病患者B细胞缺陷的确切部位仍有待确定。需要进一步研究以评估胰岛内细胞间关系紊乱在晚发型糖尿病发病机制中的作用。人类糖尿病中胰岛病理的双重模式并不排除该疾病在病因和发病机制上存在更深刻的异质性。
