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

西班牙裔人群糖尿病进展的唾液和血浆代谢组学特征

• 批准号: 9915910
• 负责人: Shilpa Nandana Bhupathiraju
• 金额: $ 56.4万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9915910
• 关键词: Address; Adult; Affect; Age-Years; American; Archives; Biological Markers; Data; Development; Diabetes Mellitus; Diet; Dietary Factors; Dietary Intervention; Disease Progression; Dyslipidemias; Epidemic; Fasting; Food; Frequencies; Functional disorder; Future; Glucose; Goals; Health; High Prevalence; Hispanics; Homeostasis; Individual; Inflammation; Insulin Resistance; Intervention; Knowledge; Life Style; Longitudinal Studies; Measures; Metabolic; Metabolic Pathway; Mexican Americans; Minority; Minority Groups; Modeling; Molecular; Names; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; OGTT; Obesity; Oral health; Outcome; Overweight; PF4 Gene; Participant; Pathway Analysis; Pathway interactions; Periodontal Diseases; Periodontitis; Plasma; Population; Prediabetes syndrome; Prospective Studies; Prospective cohort; Public Health; Puerto Rican; Puerto Rico; Questionnaires; Research; Research Project Grants; Risk Factors; Saliva; Salivary; Sampling; Specimen; Subgroup; Supervision; Work; adiponectin; aged; cardiometabolic risk; cardiometabolism; cohort; diabetes risk; endothelial dysfunction; experience; follow-up; health disparity; high risk; high risk population; indexing; insulin sensitivity; lifestyle factors; lifestyle intervention; metabolomics; multidisciplinary; network models; novel; prevent; prospective; secondary analysis

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.

项目摘要 2型糖尿病（T2D）已达到影响超过30030万美国人的流行病。 与非西班牙裔白人相比，西班牙裔具有T2D的可能性高64％。在西班牙裔小组中，波多黎各 里奇人的心脏代谢危险因素很高，包括健康饮食较低，并具有 国家严重牙周疾病的最高率。他们的可能性是墨西哥裔美国人的两倍 住院治疗糖尿病相关疾病，并确定了健康差异。尽管很高 心脏代谢风险的患病率，对基于的代谢特征和途径的理解 波多黎各人的糖尿病进展仍然有限。虽然大多数研究都使用等离子体作为 生物流体测量代谢物，唾液是一种不创易于获得的血浆替代品 与糖尿病风险有关的代谢产物。唾液也可能具有独特的疾病代谢途径 进展。在拟议的项目中，我们计划检查血浆和唾液代谢组概况 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，有一个 造成糖尿病进展的危险因素负担很大。大量数据和标本是 在基线和三年随访中收集。我们的主要目的是：1）识别基线唾液和血浆 使用的代谢组概况和与糖尿病进展相关的900多名参与者的网络使用 监督和无监督的网络分析。 2）确定唾液与血浆之间的关联 AIM 1和三年变化的心脏代谢风险因素的变化，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）的标志 炎。在二次分析中，我们将检查牙周炎是否修饰 唾液代谢产物和糖尿病进展。我们还将评估已知之间的相互关系 血浆和唾液中存在的代谢产物。此外，我们将评估 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 T2D进展的生物标志物在高风险的超重少数群体中。这项研究可能有 重要的公共卫生影响是因为新的血浆和唾液代谢产物从这项研究中确定 可能可以接受干预措施，从而有助于减少糖尿病的进展并降低健康差异。 拟议的项目建立在高风险人口中现有队列的众多优势上，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 潜力有可能在研究不足的少数群体中对糖尿病的病理生理学的理解和 所产生的知识可以直接告知将来的干预措施，以减轻糖尿病风险。