Knip Mikael, Veijola Riitta, Virtanen Suvi M, Hyöty Heikki, Vaarala Outi, Akerblom Hans K
Hospital for Children and Adolescents, University of Helsinki, P.O. Box 281, FI-00029 HUCH, Helsinki, Finland.
Diabetes. 2005 Dec;54 Suppl 2:S125-36. doi: 10.2337/diabetes.54.suppl_2.s125.
Type 1 diabetes is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing beta-cells in the pancreatic islets in genetically susceptible subjects. A series of evidence supports a critical role of exogenous factors in the development of type 1 diabetes, such as 1) the fact that <10% of individuals with HLA-conferred diabetes susceptibility do progress to clinical disease, 2) a pairwise concordance of type 1 diabetes of <40% among monozygotic twins, 3) a more than 10-fold difference in the disease incidence among Caucasians living in Europe, 4) a several-fold increase in the incidence over the last 50 years, and 5) migration studies indicating that the disease incidence has increased in population groups who have moved from a low-incidence to a high-incidence region. This article discusses the trigger-booster hypothesis claiming that the diabetic disease process is triggered by an exogenous factor with definite seasonal variation and driven by one or several other environmental determinants. In addition, there are a series of modifying factors affecting the fate and pace of the process. Accordingly, progression to clinical type 1 diabetes typically requires the unfortunate combination of genetic disease susceptibility, a diabetogenic trigger, and a high exposure to a driving antigen.
1型糖尿病被视为一种慢性免疫介导性疾病，在具有遗传易感性的个体中，其亚临床前驱期的特征是胰岛中产生胰岛素的β细胞选择性丧失。一系列证据支持外源性因素在1型糖尿病发病中起关键作用，例如：1）携带HLA糖尿病易感性的个体中，不到10%会发展为临床疾病；2）同卵双胞胎中1型糖尿病的成对一致性低于40%；3）生活在欧洲的白种人之间疾病发病率相差10倍以上；4）在过去50年中发病率增加了几倍；5）移民研究表明，从低发病率地区迁移到高发病率地区的人群中，该疾病的发病率有所增加。本文讨论了触发-增强假说，该假说认为糖尿病病程由具有明确季节性变化的外源性因素触发，并由一个或几个其他环境决定因素驱动。此外，还有一系列影响病程转归和进展速度的调节因素。因此，进展为临床1型糖尿病通常需要遗传易感性、致糖尿病触发因素以及高暴露于驱动抗原等不幸的组合。
