A classification and regression tree analysis identifies subgroups of childhood type 1 diabetes.
A classification and regression tree analysis identifies subgroups of childhood type 1 diabetes.
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DOI：
10.1016/j.ebiom.2022.104118
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发表时间：
2022-08
期刊：
影响因子：
11.1
通讯作者：
Ziegler, Anette-G
中科院分区：
文献类型：
--
作者：
Achenbach, Peter;Hippich, Markus;Zapardiel-Gonzalo, Jose;Karges, Beate;Holl, Reinhard W.;Petrera, Agnese;Bonifacio, Ezio;Ziegler, Anette-G
关键词：
儿童和青少年糖尿病包括自身免疫和非自身免疫形式，在临床和生化表现上具有异质性。一个尚未解决的问题是，在这些形式的糖尿病中是否存在亚型、内型或治疗型。多变量分类和回归树（CART）分析方法用于确定20岁之前新诊断糖尿病患者（n=1192）中残留C肽水平不同的糖尿病亚组。在确认和预后队列（n=2722）中评估了模型的稳健性。分析选择年龄，血红蛋白A1 c（HbA 1c）和体重指数（BMI）作为分裂参数，将患者分为7个胰岛自身抗体阳性组和3个自身抗体阴性组。各组之间在遗传学、炎症标志物、糖尿病家族史、血脂、25-OH-维生素D3、胰岛素治疗、胰岛素敏感性和胰岛素自身免疫性方面存在实质性差异，并且该方法将具有潜在不同病因和疾病的患者分层。在最年轻的胰岛自身抗体阳性组和C-肽值最低的患者中，干扰素-β和/或肿瘤坏死因子炎症特征富集，而在老年患者中发现较高的BMI和2型糖尿病特征。7年中位随访时HbA 1c的持续差异证明了预后相关性。多变量分析揭示了年轻糖尿病患者的亚组，具有潜在的发病机制和治疗相关性。这项工作得到了德国联邦教育和研究部（01 KX 1818; FKZ 01 GI 0805; DZD e. V.）的资金支持，创新医学倡议2联合企业INNODIA（赠款协议编号115797），德国罗伯特科赫研究所和德国糖尿病协会。
Diabetes in childhood and adolescence includes autoimmune and non-autoimmune forms with heterogeneity in clinical and biochemical presentations. An unresolved question is whether there are subtypes, endotypes, or theratypes within these forms of diabetes. The multivariable classification and regression tree (CART) analysis method was used to identify subgroups of diabetes with differing residual C-peptide levels in patients with newly diagnosed diabetes before 20 years of age (n=1192). The robustness of the model was assessed in a confirmation and prognosis cohort (n=2722). The analysis selected age, haemoglobin A1c (HbA1c), and body mass index (BMI) as split parameters that classified patients into seven islet autoantibody-positive and three autoantibody-negative groups. There were substantial differences in genetics, inflammatory markers, diabetes family history, lipids, 25-OH-Vitamin D3, insulin treatment, insulin sensitivity and insulin autoimmunity among the groups, and the method stratified patients with potentially different pathogeneses and prognoses. Interferon-ɣ and/or tumour necrosis factor inflammatory signatures were enriched in the youngest islet autoantibody-positive groups and in patients with the lowest C-peptide values, while higher BMI and type 2 diabetes characteristics were found in older patients. The prognostic relevance was demonstrated by persistent differences in HbA1c at 7 years median follow-up. This multivariable analysis revealed subgroups of young patients with diabetes that have potential pathogenetic and therapeutic relevance. The work was supported by funds from the German Federal Ministry of Education and Research (01KX1818; FKZ 01GI0805; DZD e.V.), the Innovative Medicine Initiative 2 Joint Undertaking INNODIA (grant agreement No. 115797), the German Robert Koch Institute, and the German Diabetes Association.
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影响因子：
8.2
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1198/106186006x133933
发表时间：
2006-09-01
影响因子：
2.4
作者：
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通讯作者：
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影响因子：
7.7
作者：
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Peakman M