Type 1 Diabetes
Type 1 Diabetes
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DOI：
10.1016/b978-0-12-374279-7.15001-5
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Alshiekh, Shehab
中科院分区：
文献类型：
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作者：
Lernmark, Ake;Alshiekh, Shehab
1 型糖尿病，以前称为青少年糖尿病或胰岛素依赖型糖尿病，是由胰岛 β 细胞的特异性自身免疫破坏引起的。随后缺乏胰岛素会导致血糖和尿糖升高。典型症状是多尿（尿频）、多饮（口渴增加）、多食（饥饿增加）和体重减轻。该疾病可在任何年龄诊断，但仅限于具有某些 HLA-DR-DQ 易感性单倍型的个体。一些非 HLA 遗传因素要么导致遗传病因，要么导致疾病临床发作的进展。胰岛素自身抗体 (IAA) 或 GAD65 (GADA) 的标准化测试已证明这种疾病经常在生命的最初几年引发。病毒等环境因素可能是 IAA 和 GADA 的触发因素，它们的出现方式与人类白细胞抗原 (HLA) 相关。患有 IAA、GADA 或两者的个体可能会产生其他针对 IA-2 (IA-2A)、ZnT8 转运蛋白 (ZnT8A) 或两者的自身抗体。具有两种或两种以上胰岛自身抗体的个体将继续发展为 1 型糖尿病 (100%)，但这可能需要 20 年的时间。发病机制可能是由识别 β 细胞表面表达的 HLA I 类蛋白上的自身抗原肽的 CD8(+) T 细胞控制的。临床发病的进展与 β 细胞的损失有关，并且可以通过 HLA 分型和 IAA、GADA、IA-2A 和 ZnT8A 测试来预测该疾病。预防和干预试验旨在阻止 β 细胞自身免疫过程，但这些试验的结果并没有改变治疗 1 型糖尿病患者的方式。
Type 1 diabetes, formerly known as juvenile diabetes or insulin-dependent diabetes, results from the specific autoimmune destruction of the pancreatic islet beta cells. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss. The disease may be diagnosed at any age but only in individuals who have certain HLA-DR-DQ-susceptibility haplotypes. Several non-HLA genetic factors either contribute to the genetic etiology or to the progression toward the clinical onset of the disease. Standardized tests for insulin autoantibodies (IAA) or GAD65 (GADA) have made it possible to demonstrate that the disease is triggered often during the first years of life. Environmental factors such as virus may be a triggering factor for IAA and GADA, which appear in a way that is associated with human leukocyte antigen (HLA). Individuals, who have developed IAA, GADA, or both, may develop yet other autoantibodies against IA-2 (IA-2A), ZnT8 transporter (ZnT8A), or both. Individuals with two or more islet autoantibodies will go on to develop type 1 diabetes (100%) but it may take 20 years. The pathogenesis is likely to be controlled by CD8(+) T cells recognizing autoantigen-peptides on HLA class I proteins expressed on the beta cell surface. The progression toward clinical onset is associated with a loss of beta cells, and the disease is predictable through HLA typing and test of IAA, GADA, IA-2A, and ZnT8A. Prevention and intervention trials are aiming to halt the beta cell-autoimmune process but the results of these trials have not altered the way in which to treat patients with type 1 diabetes.