NON-INVASIVE SALIVA-BASED DIABETES AUTOANTIBODY SCREENING.

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) gt98 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 accessibilityof 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 riskfor 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 onehas the auto-antibodies that are associated with diabetes risk.