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.

项目概要 2 型糖尿病 (T2D) 已达到流行病的程度，影响了超过 3030 万美国人。 西班牙裔人患 T2D 的可能性比非西班牙裔白人高 64%。在西班牙裔亚裔群体中，波多黎各 黎加人的心脏代谢危险因素普遍存在，包括不太健康的饮食，并且 全国严重牙周病发病率最高的国家。他们的可能性是墨西哥裔美国人的两倍 因糖尿病相关疾病住院并存在健康差异。尽管高 心脏代谢风险的患病率，了解其背后的代谢特征和途径 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血浆作为 生物液测量代谢物，唾液是血浆测量的一种非侵入性且易于获取的替代品 与糖尿病风险相关的代谢物。唾液还可能呈现出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特征 糖尿病进展。该研究将在来自圣胡安超重成人的参与者中进行 纵向研究（SOALS）。参与者为超重/肥胖、西班牙裔、40-65 岁，并且有 导致糖尿病进展的大量危险因素。广泛的数据和样本 在基线和三年随访时收集。我们的主要目标是： 1) 确定唾液和血浆的基线 超过 900 名参与者的代谢组学概况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关联 目标 1 中确定的代谢组学特征和心脏代谢危险因素的三年变化，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）的标志物 炎。在二次分析中，我们将检查牙周炎是否改变了两者之间的关联 唾液代谢和糖尿病进展。我们还将评估已知之间的相互关系 代谢物存在于血浆和唾液中。此外，我们将评估之间的横截面关联 代谢以及基线饮食和生活方式因素。这项研究将鉴定客观唾液和血浆 高风险超重少数群体中 T2D 进展的生物标志物。这项研究很可能有 由于本研究中发现了新的血浆和唾液代谢物，因此对公共卫生具有重要意义 可能适合干预措施，从而有助于减少糖尿病进展并缩小健康差距。 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。该项目有 有潜力增进我们对未充分研究的少数群体糖尿病病理生理学的理解， 所产生的知识可以直接为未来改善糖尿病风险的干预措施提供信息。