Nokoff Natalie J, Rewers Marian, Cree Green Melanie
Department of Pediatrics and Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
Discov Med. 2012 Feb;13(69):115-22.
Type 1 diabetes (T1D) is a common chronic disease characterized by selective autoimmune destruction of the pancreatic islet beta cells and subsequent dependence on exogenous insulin. Certain alleles including the high-risk HLA genotype, HLA-DR3-DQ2/DR4-DQ8, place individuals at increased risk of developing T1D. Autoantibodies to beta cell antigens are used in the diagnosis of T1D, and studies have shown that they can be used to predict risk of developing T1D in first degree relatives of probands. The annual global incidence of T1D is increasing by 3-5% per year. Many environmental factors have been implicated in the rising incidence of T1D. Proponents of the accelerator hypothesis argue that T1D and type 2 diabetes (T2D) are the same disorder of insulin resistance, although with different genetic backgrounds. While insulin resistance is a recognized hallmark of T2D, it also appears to play a significant role in the pathogenesis of T1D and its vascular complications. In this article, we will review: 1) immunogenetics of T1D, 2) risk factors for the development of islet autoimmunity and T1D, 3) mechanisms of insulin resistance in T1D, and 4) links between insulin resistance and complications in T1D. Further studies are needed to define environmental factors causing T1D as well as the role of insulin resistance in the pathogenesis of T1D and its complications.
1型糖尿病（T1D）是一种常见的慢性疾病，其特征是胰岛β细胞选择性自身免疫性破坏，随后依赖外源性胰岛素。某些等位基因，包括高风险的HLA基因型HLA-DR3-DQ2/DR4-DQ8，会使个体患T1D的风险增加。β细胞抗原自身抗体用于T1D的诊断，研究表明它们可用于预测先证者一级亲属患T1D的风险。全球T1D的年发病率正以每年3%至5%的速度上升。许多环境因素与T1D发病率上升有关。加速假说的支持者认为，T1D和2型糖尿病（T2D）是胰岛素抵抗的同一种疾病，尽管遗传背景不同。虽然胰岛素抵抗是T2D公认的标志，但它似乎在T1D及其血管并发症的发病机制中也起重要作用。在本文中，我们将综述：1）T1D的免疫遗传学，2）胰岛自身免疫和T1D发生的危险因素，3）T1D中胰岛素抵抗的机制，以及4）T1D中胰岛素抵抗与并发症之间的联系。需要进一步研究来确定导致T1D的环境因素以及胰岛素抵抗在T1D及其并发症发病机制中的作用。
