Diabetes Research Group, Cardiff University School of Medicine, Cardiff, UK.
Departments of Immunobiology and Internal Medicine, Yale University, New Haven, CT, USA.
Lancet. 2019 Oct 5;394(10205):1286-1296. doi: 10.1016/S0140-6736(19)32127-0. Epub 2019 Sep 15.
Over several decades, studies have described the progression of autoimmune diabetes, from the first appearance of autoantibodies until, and after, the diagnosis of clinical disease with hyperglycaemia and insulin dependence. Despite the improved management of type 1 diabetes with exogenous insulin, most patients do not meet clinical glycaemic goals, and diabetes remains an important medical problem that affects children and adults. Clinical and preclinical studies have suggested strategies to prevent the diagnosis of type 1 diabetes in people at risk, but the outcomes of previous clinical trials have not met their primary endpoints of disease prevention or delay. The results from the TN-10 teplizumab prevention trial show that the diagnosis of type 1 diabetes can be delayed by treatment with a FcR non-binding monoclonal antibody to CD3 in people at high risk for disease. This Series paper discusses how this clinical achievement raises new questions about for whom, and when, immunological strategies might be developed to prevent type 1 diabetes, and how to achieve this goal.
几十年来，研究已经描述了自身免疫性糖尿病的进展，从最初出现自身抗体到临床疾病的诊断，包括高血糖和胰岛素依赖。尽管使用外源性胰岛素改善了 1 型糖尿病的管理，但大多数患者仍未达到临床血糖目标，糖尿病仍然是一个重要的医学问题，影响儿童和成人。临床和临床前研究已经提出了预防高危人群发生 1 型糖尿病的策略，但以前的临床试验结果并未达到其预防或延迟疾病的主要终点。TN-10 特普利珠单抗预防试验的结果表明，在疾病高危人群中使用 FcR 非结合单克隆抗体治疗 CD3 可以延迟 1 型糖尿病的诊断。本系列文章讨论了这一临床成就提出了哪些新问题，即免疫策略可能针对哪些人群以及何时开发以预防 1 型糖尿病，以及如何实现这一目标。
