Type 1 diabetes pathogenesis - Prevention???
Type 1 diabetes pathogenesis - Prevention???
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DOI：
10.4103/2230-8210.155404
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发表时间：
2015-04
影响因子：
--
通讯作者：
Srikanta S
中科院分区：
文献类型：
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作者：
Krishna CS;Srikanta S
1型糖尿病的发病机制是多方面的，包括自身免疫、遗传和环境。针对胰岛细胞的自身免疫导致缓慢进行性选择性β细胞破坏（“原发性自身免疫性胰岛炎”），多年来最终临床表现为胰岛素依赖性糖尿病（IDDM）。针对胰岛内分泌细胞的循环血清自身抗体（胰岛细胞自身抗体- ICAb）是这种疾病的重要标志。胰岛细胞自身抗体的测定促进了自身免疫性糖尿病发病机制中几个方面的研究和理解。它们的应用已扩展到临床实践，并为早期临床前预测和预防性预防IDDM/1型DM开辟了新的途径。最近，令人惊讶的是，已经描述了T1 DM胰岛之间的胰岛素含量的差异，以及胰岛的“斑片状”或“小叶状”破坏。这些独特的病理生物学现象表明，β细胞破坏可能并不总是不可阻挡的和不可避免的完全/全部，因此提高了对β细胞自身免疫的可能治疗中断-破坏和治愈1型糖尿病的希望。“复发性或继发性自身免疫性胰岛炎”是指胰腺移植后胰岛细胞自身抗体的快速再现，以及在不存在任何移植胰腺排斥[单卵双胞胎对双胞胎移植]的情况下，移植胰腺中的选择性胰岛β细胞破坏[永不遗忘或“回忆性”β细胞破坏性记忆]。一个明确的环境因素是先天性风疹，因为它的一个子集的儿童随后发展为1型糖尿病。假定的诱发因素是病毒、麸质和牛奶。假定的保护因素包括肠道植物群、蠕虫、病毒感染和维生素D。T1 DM的预防可包括：自身抗体产生前的一级预防策略和自身抗体产生后的二级预防方案。一旦胰岛细胞自身抗体产生，目标是建立一种治疗方案，以保留至少90%的β细胞，并防止高血糖症的发展。T1 DM逆转的靶点应包括自身免疫、β细胞再生和β细胞群保护。抗-CD 3 teplizumab和抗-CD 3 otelixizumab已显示可提供C肽保护。糖尿病研究中尚未回答的问题包括自身免疫记忆反应的消除，免疫自身耐受的重建以及疾病启动的机制。
Pathogenesis of type 1 diabetes is multi-faceted, including, autoimmunity, genetics and environment. Autoimmunity directed against pancreatic islet cells results in slowly progressive selective beta-cell destruction (“Primary autoimmune insulitis”), culminating over years in clinically manifested insulin-dependent diabetes mellitus (IDDM). Circulating serum autoantibodies directed against the endocrine cells of the islets of Langerhans (Islet cell autoantibodies - ICAb) are an important hallmark of this disease. Assays for islet cell autoantibodies have facilitated the investigation and understanding of several facets in the pathogenesis of autoimmune diabetes. Their applications have extended into clinical practice and have opened new avenues for early preclinical prediction and preventive prophylaxis in IDDM/type 1 DM. Recently, surprisingly, differences in insulin content between T1DM islets, as well as, ‘patchy’ or ‘lobular’ destruction of islets have been described. These unique pathobiological phenomena, suggest that beta cell destruction may not always be inexorable and inevitably complete/total, and thus raise hopes for possible therapeutic interruption of beta cell autoimmunity – destruction and cure of type 1 diabetes. “Recurrent or secondary autoimmune insulitis” refers to the rapid reappearance of islet cell autoantibodies post pancreas transplant, and selective islet beta cell destruction in the grafted pancreas [never forgetting or “anamnestic” beta cell destructive memory], in the absence of any graft pancreas rejection [monozygotic twin to twin transplantation]. The one definite environmental factor is congenital rubella, because of which a subset of children subsequently develop type 1 diabetes. The putative predisposing factors are viruses, gluten and cow's milk. The putative protective factors include gut flora, helminths, viral infections, and Vitamin D. Prevention of T1DM can include: Primary prevention strategies before the development of autoantibodies and Secondary prevention regimens after autoantibody development. Once islet cell autoantibodies have developed, the goal is to establish a therapeutic regimen to preserve at least 90% of the beta cells, and prevent the development of hyperglycaemia. The targets for T1DM reversal should include autoimmunity, beta cell regeneration and protection of beta cell mass. Anti-CD3 teplizumab and anti-CD3 otelixizumab have been shown to provide C-peptide preservation. The unanswered questions in diabetes research include elimination of autoimmune memory responses, reestablishment of immune self-tolerance, and mechanisms of disease initiation.