Dahlquist G
Department of Pediatrics, University Hospital, Umeå, Sweden.
Autoimmunity. 1993;15(1):61-5. doi: 10.3109/08916939309004840.
The mechanism of beta-cell destruction leading to insulin dependent diabetes is probably a cell mediated auto-immune process occurring in genetically susceptible individuals. Since 50-70% of monozygotic twins will not get the disease non-genetic risk factors must play an important role in the etiology of the disease. During the past decade population based epidemiological studies have identified several risk determinants for insulin dependent diabetes. Based on these studies a multifactorial hypothesis of causation is proposed. Some risk determinants (maternal child blood group incompatibility, fetal viral infections, early exposure to cow's milk proteins, a high exposure level of nitrosamines) may independently initiate the autoimmune process by causing the initial damage of the beta-cell, leading to antigen release. Other risk determinants may promote an already ongoing autoimmune destructive process through induction of lymphokine release or by causing an increased work load on the beta-cell. Risk factors that may increase the peripheral need for insulin (infectious diseases, cold environment, a high growth rate and stressful life events) may act as promoters of the beta-cell destruction but also disclose the beta-cell impairment and make the disease clinically overt. Possibilities of different risk profiles in different age groups and of synergism between different risk factors are also discussed.
导致胰岛素依赖型糖尿病的β细胞破坏机制可能是一种发生在遗传易感性个体中的细胞介导的自身免疫过程。由于50%-70%的同卵双胞胎不会患这种疾病，非遗传风险因素在该疾病的病因中必定起着重要作用。在过去十年中，基于人群的流行病学研究已经确定了胰岛素依赖型糖尿病的几个风险决定因素。基于这些研究，提出了一种多因素病因假说。一些风险决定因素（母婴血型不相容、胎儿病毒感染、早期接触牛奶蛋白、高浓度亚硝胺暴露）可能通过引起β细胞的初始损伤，导致抗原释放，从而独立启动自身免疫过程。其他风险决定因素可能通过诱导淋巴因子释放或增加β细胞的工作量，促进已经在进行的自身免疫破坏过程。可能增加外周胰岛素需求的风险因素（传染病、寒冷环境、高生长率和压力性生活事件）可能既是β细胞破坏的促进因素，也会揭示β细胞损伤并使疾病在临床上显现出来。还讨论了不同年龄组不同风险概况以及不同风险因素之间协同作用的可能性。
