Type 1 diabetes genetic risk scores for the diagnosis of diabetes type in children of diverse racial and ethnic background

项目总结 目前的标准不能在诊断时对大量且不断增加的儿童糖尿病病例进行分类， 特别是在非高加索儿童中。临床病程的纵向观察 需要对糖尿病进行分类会导致有害的延误正确的治疗。诊疗中的误区 可能导致少数族裔中糖尿病并发症的发生率较高。因此，有一个关键的 需要强大的标准，可以应用于诊断，为所有种族/民族的儿童的临床决定提供信息 背景。长期目标是确定儿童糖尿病的发病特征，以便为临床提供信息。 这将有助于及时进行管理，从而最终改善不同种族/族裔儿童的结果。AS 初步数据，申请者已开发并验证了1型糖尿病(T1D)遗传风险评分 (GRS)，在患有不明糖尿病的成年人中，识别那些患有T1D的人，定义为快速胰岛素依赖；以及 我还证明了T1D GRS改进了目前对进展到T1D的预测模型 处于危险中的个人。这一应用的中心假设是T1D GRS与胰岛相结合 糖尿病发病时的自身抗体和其他因素，可用于种族/民族多样化的儿童以识别 那些患有T1D的人，定义为快速丧失C肽(β细胞功能的衡量标准)，因为这是T1D 具有临床影响最大的特点。这项建议理由是适时地描述 糖尿病，这在少数民族儿童中尤其困难，将有助于及早建立正确的 治疗，改善糖尿病结果，降低糖尿病的成本，目前糖尿病成本超过3270亿美元 每年一次。在强大的初步数据的指导下，这一假设将在种族/民族多样化的儿童中进行测试 通过评估T1D GRS结合其他因素识别患有糖尿病的人的能力 T1D，定义为胰岛素缺乏(低C肽)，在横断面(特定目标1)和前瞻性(特定目标1)中 目的2)态度。这一项目意义重大，因为它最终有望改善儿科疾病的治疗 糖尿病及其临床后果，特别是对处境不利的种族/族裔群体的影响。这个项目 是创新的，因为它试图通过提议利用遗传学来改变当前的临床和研究实践 作为一种新的、负担得起的、独立于时间的诊断T1D的策略，由临床相关的 很有特色。

PROJECT SUMMARY A large and growing number of pediatric diabetes cases cannot be classified at diagnosis with the current criteria, particularly among non-Caucasian children. The longitudinal observation of the clinical course that is often needed to classify diabetes causes harmful delays in the correct treatment. Mistakes in diagnosis and treatment may contribute to the higher frequency of diabetic complications in racial/ethnic minorities. Thus, there is a critical need for robust criteria that can be applied at diagnosis to inform clinical decisions in children of all racial/ethnic backgrounds. The long-term objective is to characterize pediatric diabetes at onset to inform clinical management in a timely fashion and thus, ultimately improve outcomes in racially/ethnically diverse children. As preliminary data, the applicants have developed and validated type 1 diabetes (T1D) Genetic Risk Scores (GRSs) that, in adults with unclear diabetes, identify those with T1D, defined by rapid insulin dependence; and have also demonstrated that a T1D GRS improves the current predictive model for progression to T1D in individuals at risk. The central hypothesis of this application is that T1D GRSs, in combination with islet autoantibodies and other factors at diabetes onset, can be used in racially/ethnically diverse children to identify those who have T1D, defined by rapid loss of C-peptide (measure of beta-cell function), as this is the T1D characteristic with the largest clinical impact. The rationale for this proposal is that timely characterization of diabetes, which is particularly difficult in minority children, will facilitate early establishment of the correct treatment, improve diabetes outcomes and lower the costs of diabetes, which are currently over $327 billion yearly. Guided by strong preliminary data, this hypothesis will be tested in racially/ethnically diverse children with diabetes by assessing the ability of T1D GRSs, in combination with other factors, to identify those who have T1D, defined as insulin deficiency (low C-peptide), in a cross-sectional (Specific Aim 1) and prospective (Specific Aim 2) manner. This project is significant because it is ultimately expected to improve the treatment of pediatric diabetes and thus its clinical outcomes, with particular impact on disadvantaged racial/ethnic groups. This project is innovative because it seeks to shift the current clinical and research practices by proposing to utilize genetics as a novel, affordable, time-independent strategy to diagnose T1D, identified by a clinically relevant characteristic.