Institue of Biomedicine, University of Turku and Clinical Microbiology, Turku University Hospital, Turku, Finland.
Department of Paediatrics, University of Turku and Turku University Hospital, Turku, Finland.
Nat Rev Endocrinol. 2019 Nov;15(11):635-650. doi: 10.1038/s41574-019-0254-y. Epub 2019 Sep 18.
Type 1 diabetes mellitus (T1DM) results from the destruction of pancreatic β-cells that is mediated by the immune system. Multiple genetic and environmental factors found in variable combinations in individual patients are involved in the development of T1DM. Genetic risk is defined by the presence of particular allele combinations, which in the major susceptibility locus (the HLA region) affect T cell recognition and tolerance to foreign and autologous molecules. Multiple other loci also regulate and affect features of specific immune responses and modify the vulnerability of β-cells to inflammatory mediators. Compared with the genetic factors, environmental factors that affect the development of T1DM are less well characterized but contact with particular microorganisms is emerging as an important factor. Certain infections might affect immune regulation, and the role of commensal microorganisms, such as the gut microbiota, are important in the education of the developing immune system. Some evidence also suggests that nutritional factors are important. Multiple islet-specific autoantibodies are found in the circulation from a few weeks to up to 20 years before the onset of clinical disease and this prediabetic phase provides a potential opportunity to manipulate the islet-specific immune response to prevent or postpone β-cell loss. The latest developments in understanding the heterogeneity of T1DM and characterization of major disease subtypes might help in the development of preventive treatments.
1 型糖尿病（T1DM）是由免疫系统介导的胰腺β细胞破坏引起的。在个体患者中，多种遗传和环境因素以不同的组合存在，参与了 T1DM 的发生。遗传风险由特定等位基因组合的存在定义，这些组合在主要易感部位（HLA 区域）影响 T 细胞对外来和自身分子的识别和耐受。其他多个基因座也调节和影响特定免疫反应的特征，并改变β细胞对炎症介质的易感性。与遗传因素相比，影响 T1DM 发展的环境因素的特征尚不明确，但与特定微生物的接触正成为一个重要因素。某些感染可能会影响免疫调节，共生微生物（如肠道微生物群）在发育中的免疫系统的教育中起着重要作用。一些证据还表明，营养因素也很重要。在临床疾病发病前数周至 20 年，循环中就会出现多种胰岛特异性自身抗体，这一糖尿病前期阶段为操纵胰岛特异性免疫反应以预防或延缓β细胞损失提供了潜在机会。对 T1DM 异质性的最新认识和主要疾病亚型的特征描述，可能有助于开发预防治疗方法。
