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

项目总结 2型糖尿病(T2D)已经达到流行的程度，影响着3030多万美国人。 与非西班牙裔白人相比，西班牙裔美国人患T2D的可能性要高出%。在西班牙裔亚群中，波多黎各 美国人心脏代谢危险因素的患病率很高，包括不太健康的饮食，而且 全国严重牙周病患病率最高。他们是墨西哥裔美国人的两倍 因糖尿病相关疾病而住院，并建立了健康差距。尽管有很高的 心脏代谢风险的流行，了解构成其基础的代谢特征和途径 在波多黎各人中，糖尿病的进展仍然有限。虽然大多数研究都使用血浆作为 生物液体测量代谢物，唾液是一种非侵入性的、容易获得的替代血浆测量的方法 与糖尿病风险相关的代谢产物。唾液也可能与疾病的不同代谢途径有关。 进步。在拟议的项目中，我们计划检测血浆和唾液的代谢图谱 糖尿病进展。这项研究将在圣胡安超重成年人的参与者中进行 纵向研究(SOALS)。参与者超重/肥胖，西班牙裔，40-65岁，有 导致糖尿病进展的风险因素负担很大。大量的数据和样本 在基线和三年的随访中收集。我们的主要目标是：1)确定基线唾液和血浆 超过900名参与者的代谢组谱和与糖尿病进展相关的网络，使用 监督和非监督网络分析。2)确定唾液和血浆之间的联系 AIM 1中确定的代谢组谱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、全身和局部(牙周炎)的标志物 发炎。在二次分析中，我们将检查牙周炎是否改变了 唾液代谢物与糖尿病进展。我们还将评估已知的 血浆和唾液中存在的代谢物。此外，我们将评估横截面之间的关联 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 高危超重少数民族人群中T2D进展的生物标志物。这项研究很可能会有 重要的公共卫生影响，因为从这项研究中确定的新的血浆和唾液代谢物 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。 拟议的项目是建立在高危人群现有队列的众多优势之上的，以及 支持我们多学科团队进行的初步工作的结果。这个项目有 在研究不足的少数民族人群中促进我们对糖尿病病理生理学的理解的潜力和 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.