NON-INVASIVE SALIVA-BASED DIABETES AUTOANTIBODY SCREENING.

描述(申请人提供)：存在胰岛导向的自身免疫和相关的循环自身抗体，以前被认为主要是1型的特征 糖尿病(T1 DM)，现在在一部分假定患有2型糖尿病(T2 DM)的人中很明显，这与人们越来越多地认识到糖尿病是一个连续的谱系是一致的。基于下列观察：1)98%的T1 DM新发病例中有一种或多种自身抗体；2)自身抗体的数量与发生T1 DM的风险成正比，任何一种自身抗体都与患T1 DM的风险增加近30倍；3)在明显患有T2 DM的青少年中存在自身抗体，定义了一个可能需要不同治疗方案的独特患者组；以及4)在假定为T2 DM的成年人中，自身抗体的存在可指示胰岛素依赖的进展更快，因此有必要在糖尿病和糖尿病前期人群中加强对自身抗体状态的筛查。接触到大量高危人群的主要障碍是缺乏一种简单易用的车载设备来快速筛查糖尿病自身免疫状态。将准确的自身抗体检测扩展到替代体液，可以促进高危患者群体获得这一重要诊断参数，以实现更具成本效益和效率的疾病检测和监测。我们的初步数据支持这样一种假设，即可以在唾液中可靠地评估糖尿病自身抗体，并且它们的检测适用于简单的护理点、基于设备的技术。为了演示此方法的实用性，我们将在此第一阶段应用程序中实现以下两个具体目标。特异性目标1：匹配的血清和唾液样本中自身抗体状态在典型T1 DM和T2 DM中的相关性。具体目标2：开发一种检测自身免疫性糖尿病的非侵入性、唾液为基础的侧流设备。这项拟议的研究通过开发“能够识别罹患1型糖尿病风险的个人的新方法和技术”，特别侧重于点式护理分析、低成本/便携式设备、非侵入性测试和免疫状态评估，与RFA-DK-11-024的目标和其中描述的许多相关主题直接相关。

DESCRIPTION (provided by applicant): The presence of islet-directed auto-immunity and associated circulating auto-antibodies, previously thought to be primarily characteristic of type-1 diabetes mellitus (T1DM), is now apparent in a proportion of individuals with putative type-2 diabetes (T2DM), consistent with an increasing appreciation of diabetes as a continuous spectrum. Based on the observations that: 1) >98 percent of new-onset cases of T1DM have one or more auto-antibodies; 2) the number of auto-antibodies is proportional to risk of developing T1DM, with any one corresponding to an almost 30-fold increase in risk; 3) the presence of auto-antibodies in adolescents with apparent T2DM defines a distinct patient group that may require different treatment regimens; and 4) the presence of auto-antibodies in adults with presumed T2DM can indicate a more rapid progression to insulin dependency, increased screening for autoantibody status in diabetic and pre-diabetic populations is warranted. The major hurdle for reaching the large at-risk population is the lack of a simple-to-use, point-of-car device to rapidly screen for diabetes autoimmune status. The extension of accurate autoantibody detection to alternative body fluids can facilitate the accessibility of this importan diagnostic parameter to at-risk patient groups for more cost-effective and efficient disease detection and monitoring. Our preliminary data support the hypothesis that diabetes auto-antibodies can be reliably assessed in saliva and that their detection is amenable to simple point- of-care, device-based technologies. To demonstrate the utility of this approach, we will pursue the following two Specific Aims in this phase-I application. Specific aim 1: Correlation of autoantibody status in matched serum and saliva samples in classical T1DM and in T2DM. Specific aim 2: Development of a non-invasive, saliva-based, lateral-flow device for detection of autoimmune diabetes. The proposed research, by developing "new methods and technologies able to identify individuals at risk of developing type-1 diabetes" with a specific focus on point-f-care assays, low-cost/portable devices, non-invasive testing, and assessment of immune status, is directly relevant to the goals of RFA-DK-11-024 and many of the relevant topics described therein.