NON-INVASIVE SALIVA-BASED DIABETES AUTOANTIBODY SCREENING.

描述（由申请人提供）：存在胰岛定向自身免疫和相关循环自身抗体，以前认为是1型的主要特征 糖尿病（T1 DM），现在在一定比例的推定的2型糖尿病（T2 DM）个体中是明显的，这与糖尿病作为连续谱的增加的认识一致。基于以下观察结果：1）> 98%的新发T1 DM病例具有一种或多种自身抗体; 2）自身抗体的数量与发展为T1 DM的风险成比例，任何一种抗体对应于风险增加近30倍; 3）明显T2 DM青少年中自身抗体的存在定义了一个可能需要不同治疗方案的独特患者组;和4）在假定患有T2 DM的成人中自身抗体的存在可以指示更快地进展为胰岛素依赖，在糖尿病和前驱糖尿病人群中增加对自身抗体状态的筛查是必要的。接触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这一重要诊断参数对高危患者群体的可及性，从而实现更具成本效益和更有效的疾病检测和监测。我们的初步数据支持这样的假设，即糖尿病自身抗体可以在唾液中可靠地评估，并且它们的检测适合于简单的基于设备的即时护理技术。为了证明这种方法的实用性，我们将在第一阶段申请中实现以下两个具体目标。具体目的1：经典T1 DM和T2 DM患者匹配血清和唾液样本中自身抗体状态的相关性。具体目标2：开发一种用于检测自身免疫性糖尿病的非侵入性、基于唾液的侧流装置。 拟议的研究通过开发“能够识别有发生1型糖尿病风险的个体的新方法和技术”，特别关注即时护理测定、低成本/便携式设备、非侵入性检测和免疫状态评估，与RFA-DK-11-024的目标和其中描述的许多相关主题直接相关。 公共卫生相关性：糖尿病的发病率在美国和全世界都达到了流行病的比例，预计患有其他严重并发症（如心脏、肾脏和眼睛疾病以及认知能力下降）的个体数量将大幅增加。一个重要的问题是缺乏一种简单、廉价和方便的方法来检测患有自身免疫性糖尿病的人。容易识别可能有自身免疫性糖尿病发展风险的人的能力对于预防急性、危及生命的疾病以及采取措施延迟或预防疾病进展至关重要。这项申请中提出的研究将调查在唾液而不是血液中测量反映糖尿病风险的抗体的可行性，并开发一种简单的非侵入性 类似于家用妊娠测试的测试设备，适用于医疗办公室，家庭和现场使用，以确定是否有与糖尿病风险相关的自身抗体。

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. PUBLIC HEALTH RELEVANCE: The incidence of diabetes is reaching epidemic proportions in the US and the world at large, with projected massive increases in the number of individuals with additional serious complications such as heart, kidney, and eye disease and cognitive decline. A significant problem is the lack of a simple, inexpensive, and convenient approach to detect persons with autoimmune diabetes. The ability to easily identify people that may be at risk for the development of autoimmune diabetes is critical to prevent acute, life-threatening conditions as well as to institute measures to delay or prevent the progression of the disease. The research proposed in this application will investigate the feasibility of measuring antibodies that reflect the risk of diabetes in saliva rather than in blood, and develop a simple non-invasive test device similar to a home pregnancy test that will be suitable for medical office, home, and field use to determine if one has the auto-antibodies that are associated with diabetes risk.