NON-INVASIVE SALIVARY ASSESSMENT OF PREDIABETES AND DIABETES

描述(申请人提供)：肥胖和糖尿病的双重流行威胁着美国和世界各地的医疗体系，目前有近2900万美国人患有坦率的糖尿病(主要是2型糖尿病)，另外还有6800万人患有糖尿病前期。越来越多的证据表明牙周病和糖尿病是相关的，这种联系得到了我们发现的糖尿病唾液生物标记物的支持。应对糖尿病负担的一个主要挑战是，由于缺乏非侵入性的医疗保健点检测，我们无法轻松和方便地在高危人群中检测糖尿病和糖尿病前期。目前测定葡萄糖稳态的标准，即口服葡萄糖耐量试验或血红蛋白A1c，价格昂贵，需要去医院就诊，这对弱势人群来说是一个问题，导致了困扰糖尿病检测、护理和预防的健康差距。组成这一第一阶段提案的研究的目标是验证糖尿病和糖尿病前期唾液生物标记物的有效性。计划中的第二阶段研究将评估生物标记物的子集的性能，并将优化的分析纳入有效的设备设计，以便开发一种快速、非侵入性的多分析诊断测试，用于准确评估糖尿病前期或直接糖尿病，优于现有的基于葡萄糖的参数。糖尿病唾液检测的成功开发将对有效管理这一严重的公共卫生危机产生重大影响。这种方法的简单性和非侵入性也将在发展中国家受益。除了对糖尿病的检测和监测有潜在的直接影响外，糖尿病唾液生物标志物的引入将极大地扩大唾液诊断的范围。虽然人们对唾液作为一种诊断液一直很感兴趣，但迄今为止，唾液在人类疾病中的实际应用仅限于少数几个例子，如艾滋病毒检测和滥用药物。我们相信，这项应用中提出的唾液糖尿病检测的成功开发将增加人们对唾液作为诊断液的优势的认识，并鼓励其在临床诊断中的广泛使用。 与公共卫生相关：在美国和全世界，糖尿病的发病率正在达到流行病的比例，预计患有其他严重并发症(如心脏、肾脏和眼睛疾病)和认知能力下降的个人数量将大幅增加。糖尿病和牙周病都是慢性炎症性疾病，越来越多的人认为这两种疾病是相互关联的。具体地说，糖尿病是严重牙周炎和牙周炎的危险因素，牙周炎是血糖控制不佳的危险因素，可能还会导致糖尿病并发症。一个重大问题是缺乏一种简单、廉价和方便的方法来检测糖尿病或糖尿病前期患者，以指导他们进行适当的治疗，以预防或延缓更严重疾病的发展。根据口腔疾病和糖尿病相关的证据，我们之前在唾液中发现了与糖尿病相关的蛋白质。该项目将在临床验证研究中确定这些唾液蛋白质准确预测糖尿病和糖尿病前驱疾病的能力，并将为将一组这些蛋白质整合到一种简单的非侵入性测试设备中提供基础，该设备将适用于医疗办公室、家庭和现场使用。

DESCRIPTION (provided by applicant): The twin epidemics of obesity and diabetes threaten to overwhelm healthcare systems in the U.S. and worldwide, with almost 29 million Americans currently having frank diabetes (predominantly type-2; T2DM) and an additional 68 million with prediabetes. There is increasing evidence that periodontal disease and diabetes are related, and this connection is supported by our discovery of salivary biomarkers of diabetes. A major challenge in dealing with the burden of diabetes is our inability to easily and conveniently detect diabetes and prediabetes in at-risk populations due to the lack of a non-invasive, point-of-care test. The current standards for glucose homeostasis determination, i.e., oral glucose tolerance test or hemoglobin A1c, are expensive and requires hospital visits that are an issue for disadvantaged populations, contributing to the health disparities that plague diabetes testing, care, and prevention. The goal of the studies that comprise this Phase-I proposal is to validate novel salivary biomarkers of diabetes and prediabetes. Planned Phase-II studies will assess the performance of a subset of biomarkers and will incorporate optimized analytes into an efficient device design in order to develop a rapid, non-invasive, multi-analyte diagnostic test for accurate assessment of prediabetes or frank diabetes that is superior to existing glucose-based parameters. Successful development of salivary testing for diabetes will have a significant impact on the effective management of this critical public health crisis. The simplicity and non-invasive aspects of this approach will also be of benefit in the developing world. In addition to a potential direct impact on diabetes detection and monitoring, the introduction of salivary biomarkers for diabetes will greatly expand the scope of salivary diagnostics. While there has been intense interest in saliva as a diagnostic fluid, the practical application of saliva to human disease to date has been limited to a few examples such as testing for HIV and drugs of abuse. We believe that the successful development of salivary diabetes testing as proposed in this application will increase the appreciation of the advantages of saliva as a diagnostic fluid and encourage the expansion of its use in clinical diagnostics. 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. Diabetes and periodontal disease are both chronic inflammatory illnesses, and there is a growing consensus that these two disorders are interrelated. Specifically, diabetes is a risk factor for severe gingivitis and periodontitis, and periodontitis is a risk factor for poor glycemic control and, possibly, diabetic complications. A significant problem is the lack of a simple, inexpensive, and convenient approach to detect persons with diabetes or prediabetes to direct them to suitable treatments to prevent or delay development of more serious disease. Based upon the evidence that oral disease and diabetes are related, we have previously discovered proteins in saliva that correlate with diabetes. This project will determine the ability of these salivary proteins to accurately predict the presence of diabetes and prediabetes in a clinical validation study, and will provide the foundation for incorporation of a set of these proteins into a simple non-invasive test device that will be suitable for medical office, home, and field use.