Center for Computational Health, IBM Research, Cambridge, MA, USA.
Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
Nat Commun. 2022 Mar 21;13(1):1514. doi: 10.1038/s41467-022-28909-1.
Development of islet autoimmunity precedes the onset of type 1 diabetes in children, however, the presence of autoantibodies does not necessarily lead to manifest disease and the onset of clinical symptoms is hard to predict. Here we show, by longitudinal sampling of islet autoantibodies (IAb) to insulin, glutamic acid decarboxylase and islet antigen-2 that disease progression follows distinct trajectories. Of the combined Type 1 Data Intelligence cohort of 24662 participants, 2172 individuals fulfill the criteria of two or more follow-up visits and IAb positivity at least once, with 652 progressing to type 1 diabetes during the 15 years course of the study. Our Continuous-Time Hidden Markov Models, that are developed to discover and visualize latent states based on the collected data and clinical characteristics of the patients, show that the health state of participants progresses from 11 distinct latent states as per three trajectories (TR1, TR2 and TR3), with associated 5-year cumulative diabetes-free survival of 40% (95% confidence interval [CI], 35% to 47%), 62% (95% CI, 57% to 67%), and 88% (95% CI, 85% to 91%), respectively (p < 0.0001). Age, sex, and HLA-DR status further refine the progression rates within trajectories, enabling clinically useful prediction of disease onset.
胰岛自身免疫的发展先于 1 型糖尿病的发生,但自身抗体的存在并不一定会导致明显的疾病,临床症状的出现也难以预测。在这里,我们通过对胰岛素、谷氨酸脱羧酶和胰岛抗原-2的胰岛自身抗体(IAb)进行纵向采样,表明疾病的进展遵循不同的轨迹。在 24662 名参与者的 1 型数据智能联合队列中,有 2172 人符合至少两次随访和 IAb 阳性的标准,其中 652 人在研究的 15 年期间进展为 1 型糖尿病。我们开发的连续时间隐马尔可夫模型用于根据收集的数据和患者的临床特征发现和可视化潜在状态,表明参与者的健康状况从 11 个不同的潜在状态进展为三个轨迹(TR1、TR2 和 TR3),分别有 5 年无糖尿病累积生存率为 40%(95%置信区间[CI],35%至 47%)、62%(95%CI,57%至 67%)和 88%(95%CI,85%至 91%)(p<0.0001)。年龄、性别和 HLA-DR 状态进一步细化了轨迹内的进展速度,从而能够对疾病的发病进行有临床意义的预测。