Hyöty Heikki
JDRF Center for Prevention of Type 1 Diabetes, Tampere, Finland.
Ann Med. 2002;34(3):138-47.
Type 1 (insulin-dependent) diabetes is a typical organ-specific autoimmune disease where insulin-producing beta cells are destroyed by immune mediated mechanisms. The risk of the disease is modulated by genetic factors, mainly genes coding for human leukocyte antigens (HLA), but environmental factors are needed to trigger the process in genetically susceptible individuals. Possible viral triggers of the disease have been sought for years but their identification has been very difficult. Recently, considerable progress has been made by employing new research methods which have supported the idea that the group of enteroviruses may be particularly important in the pathogenesis. An association between enterovirus infections and type 1 diabetes was first reported 30 years ago and since then evaluated in several studies. Recent molecular studies have considerably strengthened this hypothesis by showing that enterovirus genome is present in the blood of diabetic patients. In addition, the first prospective studies have suggested that enterovirus infections may initiate the beta-cell damaging process several years before clinical diabetes is diagnosed. Ecological studies have also indicated similarities in the epidemiology of type 1 diabetes and poliomyelitis - a well-known enterovirus disease. Experimental models, like enterovirus-infected mice or in vitro-cultured beta cells, have provided important information about possible mechanisms, but still it is not known how beta cells are destroyed in human beings. The ongoing prospective studies will answer many open questions, and should the association still hold true, intervention trials will be needed to confirm causality. Even if enterovirus infections were not associated with all diabetes cases but rather with a subgroup of them, this would offer attractive possibilities to prevent the disease or part of it, for example, by an enterovirus vaccine.
1型(胰岛素依赖型)糖尿病是一种典型的器官特异性自身免疫性疾病,其中产生胰岛素的β细胞被免疫介导机制破坏。该疾病的风险受遗传因素调节,主要是编码人类白细胞抗原(HLA)的基因,但需要环境因素来触发遗传易感个体中的这一过程。多年来一直在寻找该疾病可能的病毒触发因素,但其鉴定非常困难。最近,采用新的研究方法取得了相当大的进展,这些方法支持了肠道病毒组在发病机制中可能特别重要的观点。肠道病毒感染与1型糖尿病之间的关联首次报道于30年前,此后在多项研究中进行了评估。最近的分子研究通过显示糖尿病患者血液中存在肠道病毒基因组,大大加强了这一假说。此外,首批前瞻性研究表明,肠道病毒感染可能在临床糖尿病诊断前数年就启动β细胞损伤过程。生态学研究也表明1型糖尿病和脊髓灰质炎(一种著名的肠道病毒疾病)在流行病学上存在相似之处。实验模型,如肠道病毒感染的小鼠或体外培养的β细胞,提供了有关可能机制的重要信息,但仍不清楚人类β细胞是如何被破坏的。正在进行的前瞻性研究将回答许多悬而未决的问题,如果这种关联仍然成立,将需要进行干预试验来证实因果关系。即使肠道病毒感染并非与所有糖尿病病例相关,而只是与其中一个亚组相关,这也将为预防该疾病或其一部分提供有吸引力的可能性,例如通过肠道病毒疫苗。