NON-INVASIVE SALIVARY ASSESSMENT OF PREDIABETES AND DIABETES

描述（由申请人提供）：肥胖和糖尿病的双重流行威胁着美国和全世界的医疗保健系统，目前有近2900万美国人患有糖尿病（主要是2型糖尿病和2型糖尿病），另有6800万美国人患有前驱糖尿病。越来越多的证据表明牙周病和糖尿病相关，而我们发现的糖尿病唾液生物标志物支持了这种联系。应对糖尿病负担的一个主要挑战是，由于缺乏一种非侵入性的即时检测方法，我们无法轻松方便地在高危人群中检测糖尿病和前驱糖尿病。目前的葡萄糖稳态测定标准，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，这对弱势群体来说是一个问题，造成了困扰糖尿病检测、护理和预防的健康差距。包括i期提案的研究目标是验证糖尿病和前驱糖尿病的新型唾液生物标志物。计划中的ii期研究将评估一部分生物标志物的性能，并将优化的分析物纳入有效的设备设计中，以开发一种快速、无创、多分析物的诊断测试，以准确评估前驱糖尿病或直接糖尿病，优于现有的基于葡萄糖的参数。唾液检测糖尿病的成功发展将对有效管理这一重大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对发展中国家有益。除了对糖尿病的检测和监测有潜在的直接影响外，唾液生物标志物的引入将大大扩大唾液诊断的范围。虽然人们对唾液作为一种诊断液体有着浓厚的兴趣，但迄今为止，唾液在人类疾病中的实际应用仅限于艾滋病毒检测和滥用药物等少数例子。我们相信，本应用程序中提出的唾液糖尿病检测的成功发展将增加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应用。

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.