Harrison L C
Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Australia.
Pediatr Diabetes. 2001 Jun;2(2):71-82. doi: 10.1034/j.1399-5448.2001.002002071.x.
Circulating antibodies to pancreatic beta-cell antigens are markers of islet autoimmunity. In first-degree relatives of persons with type 1 diabetes, the levels and range of antigen specificities of these islet antibodies reflect the risk for clinical diabetes. However, in the general population, in which the disease prevalence is up to 30-fold lower, the predictive value of islet antibodies is correspondingly less. Islet antibody assays are primarily research tools to identify 'prediabetic' individuals for secondary prevention trials, but can also discriminate type 1 diabetes in several clinical situations. Loss of first-phase insulin response (FPIR) to intravenous glucose signifies imminent diabetes, but FPIR is normal in most islet-antibody-positive individuals. The contribution of a single FPIR measurement to risk assessment is therefore limited, but rate of fall of FPIR may be a useful predictor. Although beta cells are destroyed by autoreactive T cells, the assay of islet antigen-reactive T cells is not routine. Genetically, the major histocompatibility complex encoding human leukocyte antigen (HLA) alleles accounts for about 50% of familial clustering of type 1 diabetes. HLA typing is not diagnostic, but can be used to differentiate high- from low-risk individuals, e.g. at birth. While 'preclinical' diagnosis raises important medical and ethical questions, an optimized screening strategy provides a basis for counselling and follow-up. Recent knowledge of disease mechanisms and 'proof-of-principle' in the non-obese diabetic (NOD) mouse model justify expectations that type 1 diabetes is preventable, and even intervention that only delays onset of clinical diabetes is likely to be cost-effective.
循环中针对胰腺β细胞抗原的抗体是胰岛自身免疫的标志物。在1型糖尿病患者的一级亲属中，这些胰岛抗体的抗原特异性水平和范围反映了临床糖尿病的风险。然而，在疾病患病率低至30倍的普通人群中，胰岛抗体的预测价值相应较低。胰岛抗体检测主要是用于识别“糖尿病前期”个体以进行二级预防试验的研究工具，但在几种临床情况下也可用于鉴别1型糖尿病。静脉注射葡萄糖后第一相胰岛素反应（FPIR）丧失预示即将发生糖尿病，但大多数胰岛抗体阳性个体的FPIR正常。因此，单次FPIR测量对风险评估的贡献有限，但FPIR的下降速率可能是一个有用的预测指标。虽然β细胞被自身反应性T细胞破坏，但胰岛抗原反应性T细胞检测并非常规检测项目。从遗传学角度来看，编码人类白细胞抗原（HLA）等位基因的主要组织相容性复合体约占1型糖尿病家族聚集性的50%。HLA分型不能用于诊断，但可用于区分高风险和低风险个体，例如在出生时。虽然“临床前期”诊断引发了重要的医学和伦理问题，但优化的筛查策略为咨询和随访提供了基础。最近对疾病机制的认识以及非肥胖糖尿病（NOD）小鼠模型中的“原理验证”证明了1型糖尿病是可预防的这一期望是合理的，甚至仅延迟临床糖尿病发病的干预措施可能也具有成本效益。
