Saliva and Plasma Metabolomic Signatures of Diabetes Progression in a Hispanic Cohort

项目摘要 2型糖尿病（T2D）已达到流行病的比例，影响超过3030万美国人。 西班牙裔比非西班牙裔白人患T2D的可能性高64%。在西班牙裔群体中，波多黎各 哥斯达黎加人有很高的心脏代谢危险因素，包括不健康的饮食， 严重牙周病的发病率是全国最高的他们是墨西哥裔美国人的两倍， 因糖尿病相关疾病住院治疗，并建立了健康差距。尽管高 心脏代谢风险的患病率，对代谢特征和代谢途径的理解， 糖尿病的进展在波多黎各人中仍然有限。虽然大多数研究使用血浆作为 生物流体来测量代谢物，唾液是一种非侵入性的容易获得的替代血浆来测量 与糖尿病风险相关的代谢物。唾液也可能存在不同的疾病代谢途径 进展在拟议的项目中，我们计划检查血浆和唾液代谢组学概况， 糖尿病进展。本研究将在来自圣胡安超重成人的受试者中进行 纵向研究（SOALS）。参与者超重/肥胖，西班牙裔，40 - 65岁， 导致糖尿病进展的大量危险因素。广泛的数据和标本， 在基线和三年随访时收集。我们的主要目标是：1）确定基线唾液和血浆 在900多名参与者中，使用代谢组学特征和与糖尿病进展相关的网络， 监督和无监督网络分析。2)为了确定唾液和血浆之间的联系 aim 1中确定的代谢组学特征和心脏代谢风险因素的三年变化，包括 血脂异常、内皮功能障碍、脂联素以及全身和局部（牙周炎） 炎症在二次分析中，我们将检查牙周炎是否改变了 唾液代谢物和糖尿病进展。我们还将评估已知的 存在于血浆和唾液中的代谢物。此外，我们还将评估 代谢物和基线饮食和生活方式因素。这项研究将确定客观的唾液和血浆 在高风险超重少数人群中T2D进展的生物标志物。这项研究很可能 重要的公共卫生意义，因为新的血浆和唾液代谢物从这项研究中发现， 可能会受到干预，从而有助于减少糖尿病的进展和降低健康差距。 拟议的项目建立在高风险人群现有队列的众多优势之上，并且 支持我们的多学科团队进行的初步工作的结果。该项目具有 有可能促进我们对未充分研究的少数人群中糖尿病病理生理学的理解， 所产生的知识可以直接为未来的干预措施提供信息，以改善糖尿病风险。

PROJECT SUMMARY Type 2 diabetes (T2D) has reached epidemic proportions affecting more than 30.3 million Americans. Hispanics are 64% more likely to have T2D than non-Hispanic whites. Among Hispanic sub-groups, Puerto Ricans have a high prevalence of cardiometabolic risk factors including less healthful diets and have the nation's highest rates of severe periodontal disease. They are twice as likely as Mexican Americans to be hospitalized for diabetes related conditions and have established health disparities. Despite the high prevalence of cardiometabolic risk, an understanding of the metabolic signatures and pathways that underlie the progression of diabetes remains limited in Puerto Ricans. While most studies have used plasma as a biofluid to measure metabolites, saliva is a non-invasive easily accessible alternative to plasma to measure metabolites related to diabetes risk. Saliva may also present with distinct metabolic pathways for disease progression. In the proposed project, we plan to examine both plasma and saliva metabolomic profiles of diabetes progression. The study will be conducted among participants from the San Juan Overweight Adults Longitudinal Study (SOALS). Participants are overweight/obese, Hispanic, 40-65 years of age, and have a large burden of risk factors that contribute to diabetes progression. Extensive data and specimens were collected at baseline and three-year follow-up. Our primary aims are: 1) To identify baseline saliva and plasma metabolomic profiles and networks associated with diabetes progression in over 900 participants, using supervised and unsupervised network analyses. 2) To determine the association between saliva and plasma metabolomic profiles identified in aim 1 and three-year changes in cardiometabolic risk factors, including markers of dyslipidemia, endothelial dysfunction, adiponectin, and systemic and local (periodontitis) inflammation. In secondary analyses, we will examine whether periodontitis modifies the association between saliva metabolites and diabetes progression. We will also evaluate inter-relationships between known metabolites present in plasma and saliva. In addition, we will evaluate cross-sectional associations between metabolites and baseline diet and lifestyle factors. This research will identify objective saliva and plasma biomarkers of T2D progression in a high-risk overweight minority population. This study is likely to have important public health implications because the novel plasma and saliva metabolites identified from this study may be amenable to interventions, thus helping to reduce diabetes progression and lower health disparities. The proposed project is built on the numerous strengths of an existing cohort in a high-risk population, and supporting results from the preliminary work conducted by our multi-disciplinary team. This project has the potential to advance our understanding of diabetes pathophysiology in an understudied minority population and the knowledge produced can directly inform future interventions to ameliorate diabetes risk.