美国西北太平洋国家实验室William A. Hagopian研究组近日取得一项新成果。经过不懈努力，他们发现综合风险评分可增强对易感儿童患1型糖尿病（T1D）的预测。相关论文发表在2020年8月7日的《自然-医学》杂志上。

为了解决T1D难预测的问题，研究人员密切关注了7798名高危儿童从出生至9.3岁时，其固定和可变因素（遗传、临床和免疫）的综合风险评分，以实现对T1D发病风险准确、高效的预测。与单独自身抗体相比，该组合模型显著改善了≥2岁时T1D的预测并且扩展到≥8岁的水平（≥接收者工作特征曲线下的面积≥0.9的区域），将基于人群新生儿酮酸中毒筛查的评估效率提高了一倍，并可以进行个性化风险评估，以更好地进行预防性试验选择。

据了解，T1D是一种自身免疫性疾病，患者胰岛受损导致胰岛素缺乏。T1D在生命早期阶段发生，这时胰岛自身抗体出现预示着高患病风险。但是，临床糖尿病可能会在几周后或在几十年后出现，并且很难预测。在发病初期酮酸中毒是很常见的并且在年轻的时候最为严重，其中可能危及生命，难以治疗。自身抗体监测程序可有效预防大多数酮酸中毒，但需要经常评估，费用限制了其应用。当存在更大胰岛肿块时，在发病前进行预防性治疗几乎是不可能的，因为很难确定最大T1D患病风险的个体。

附：英文原文

Title: A combined risk score enhances prediction of type 1 diabetes among susceptible children

Author: Lauric A. Ferrat, Kendra Vehik, Seth A. Sharp, ke Lernmark, Marian J. Rewers, Jin-Xiong She, Anette-G. Ziegler, Jorma Toppari, Beena Akolkar, Jeffrey P. Krischer, Michael N. Weedon, Richard A. Oram, William A. Hagopian

Issue&Volume: 2020-08-07

Abstract: Type 1 diabetes (T1D)—an autoimmune disease that destroys the pancreatic islets, resulting in insulin deficiency—often begins early in life when islet autoantibody appearance signals high risk1. However, clinical diabetes can follow in weeks or only after decades, and is very difficult to predict. Ketoacidosis at onset remains common2,3 and is most severe in the very young4,5, in whom it can be life threatening and difficult to treat6,7,8,9. Autoantibody surveillance programs effectively prevent most ketoacidosis10,11,12 but require frequent evaluations whose expense limits public health adoption13. Prevention therapies applied before onset, when greater islet mass remains, have rarely been feasible14 because individuals at greatest risk of impending T1D are difficult to identify. To remedy this, we sought accurate, cost-effective estimation of future T1D risk by developing a combined risk score incorporating both fixed and variable factors (genetic, clinical and immunological) in 7,798 high-risk children followed closely from birth for 9.3years. Compared with autoantibodies alone, the combined model dramatically improves T1D prediction at ≥2years of age over horizons up to 8years of age (area under the receiver operating characteristic curve≥0.9), doubles the estimated efficiency of population-based newborn screening to prevent ketoacidosis, and enables individualized risk estimates for better prevention trial selection.

DOI: 10.1038/s41591-020-0930-4

Source: https://www.nature.com/articles/s41591-020-0930-4