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The Impact of Interventions to Treat Incident Diabetes on Circulating microRNAs in the Diabetes Prevention Program

糖尿病预防计划中治疗糖尿病的干预措施对循环 microRNA 的影响

基本信息

批准号：
10545053
负责人：
Elena Flowers
金额：
$ 52.36万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-02 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10545053
关键词：
Adult Anticoagulants Behavior Biological Blood Blood Glucose Characteristics Clinical Collection Complex Conduct Clinical Trials Cross-Sectional Studies Data Development Diabetes Mellitus Disease Environment Environmental Risk Factor Etiology Fasting Flow Cytometry Funding Gene Expression Genetic Genetic Predisposition to Disease Genomics Heparin Impairment Incidence Individual Insulin Intervention Knowledge Life Style Longitudinal Studies Measures Metformin MicroRNAs Mission Modeling National Institute of Diabetes and Digestive and Kidney Diseases Nature Non-Insulin-Dependent Diabetes Mellitus Observational Study Overweight Participant Physical activity Placebos Plasma Precision Health Public Health Risk Risk Factors Risk Reduction Sampling Specimen Testing Time United States United States National Institutes of Health Weight Yoga arm circulating microRNA cohort cost detection assay diabetes prevention program extracellular group intervention improved insight inter-individual variation lifestyle factors lifestyle intervention novel marker novel strategies pharmacologic phenotypic data precision medicine predicting response predictive marker prevent randomized, clinical trials response risk prediction sample collection treatment arm

项目摘要

Circulating MicroRNAs Associated with Intensive Lifestyle Intervention and Metformin in the Diabetes Prevention Program Cohort Project summary Type 2 diabetes is priority for both public health and precision medicine. The etiology of type 2 diabetes is complex and both genetic and lifestyle/environmental factors contribute to risk. Current approaches to risk prediction and risk reduction are limited because they fail to account for the interactions between biological and lifestyle risk factors. MicroRNAs regulate expression of genes in response to lifestyle factors and capture the combined effects of genetic predisposition and the environment. Extracellular circulating microRNAs, which are readily detectable in blood, are emerging as useful indicators of disease etiology and show changes in response to the environment and behaviors. Our own prior studies and others have provided preliminary information about microRNAs as predictive biomarkers for incident type 2 diabetes and responses to risk reduction interventions. We showed that circulating microRNAs are associated with risk for type 2 diabetes, response to an insulin sensitizing pharmacologic agent, and lifestyle interventions (e.g., yoga, physical activity). Prior studies have been primarily cross-sectional in nature and were not powered to evaluate clusters of microRNAs as predictive markers. This study will determine whether microRNAs predict incident type 2 diabetes and whether there are interactions with risk reduction interventions. We will measure microRNAs in a subset of plasma samples banked at the NIDDK biorespository from participants in the completed NIH-funded Diabetes Prevention Program (DPP) trial that tested the effect of metformin, intensive lifestyle intervention, and placebo on risk for type 2 diabetes. This trial showed intensive lifestyle intervention decreased incidence of type 2 diabetes by 58% and metformin by 31% compared to placebo. The existing phenotypic data and biologic specimens from the DPP trial provide an exceptional opportunity to evaluate the relationships between longitudinal changes in both microRNAs and risk for type 2 diabetes in an extremely well characterized sample of individuals who underwent interventions that decreased incidence of type 2 diabetes. Circulating microRNAs will be measured using a flow cytometry- based direct detection assay that is compatible with heparin, the anticoagulant used for sample collection in the DPP trial. This study will be the first to evaluate, in a large, rigorously conducted clinical trial, microRNAs, singularly and as clusters, as predictors of type 2 diabetes and interactions with risk reduction interventions. This will also be the first study to model longitudinal trajectories of microRNAs and fasting blood glucose over time. This knowledge will improve our understanding of inter-individual variability in risk prediction, optimization of risk reduction interventions, and mechanisms for type 2 diabetes and responses to risk reduction interventions.

循环microrna与强化生活方式干预和二甲双胍在糖尿病中的作用