Metabolomic Biomarkers Predictors of Long-term Success Following Bariatric surgery

减肥手术后长期成功的代谢组生物标志物预测因素

• 批准号: 9310550
• 负责人: BLANDINE B LAFERRERE
• 金额: $ 3.04万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-22 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9310550
• 关键词: Amino Acids; Award; Behavioral; Beta Cell; Bile Acids; Bile fluid; Biochemical Pathway; Biological; Biological Markers; Body Composition; Body Weight Changes; Body Weight decreased; Body mass index; Branched-Chain Amino Acids; Caloric Restriction; Cell physiology; Choline; Clinical; Clinical Trials; Comorbidity; Data; Diabetes Mellitus; Disease remission; Eating; Failure; Follow-Up Studies; Gastric Bypass; Goals; Health; Health Personnel; Heterogeneity; Indium; Individual; Intervention; Link; Mass Spectrum Analysis; Measures; Metabolic; Metabolic Diseases; Metabolism; Methods; Modeling; Molecular; Molecular Target; Morbid Obesity; Non-Insulin-Dependent Diabetes Mellitus; Operative Surgical Procedures; Outcome; Pathway Analysis; Pathway interactions; Patients; Pattern; Predictive Value; Procedures; Relapse; Research Infrastructure; Resolution; Risk; Sampling; Surgeon; Testing; Time; Volatile Fatty Acids; Weight; Work; bariatric surgery; base; circulating biomarkers; clinical predictors; experience; follow-up; glucose metabolism; improved; insulin sensitivity; intervention effect; lifestyle intervention; lipid metabolism; metabolic profile; metabolomics; microbiome; novel; novel marker; obesity treatment; personalized approach; preference; response; restoration; success; treatment choice; weight loss intervention

 DESCRIPTION (provided by applicant): The sustainability of bariatric surgery on weight loss and metabolic benefits is highly variable between surgery types and individuals. In addition the mechanisms of the superior effect of gastric bypass (GBP) compared to restrictive procedures are not known. Our specific goals are: 1) To identify biomarker predictors of long-term weight loss and metabolic improvement after bariatric surgery; and 2) To identify the different mechanisms by which GBP and adjustable gastric banding (LAGB) exert their effects, i.e. to characterize mechanisms underlying the superior metabolic effects of GBP vs. LAGB. To achieve these goals we will apply metabolomic profiling to samples collected from well-characterized patients that have undergone GBP and LAGB and followed up to 7 years in the Longitudinal Assessment of Bariatric Surgery (LABS) study, and will compare them to non-operated controls with T2DM , matched on initial BMI, who participated in a lifestyle intervention (LSI) from the Action for Health in Diabetes (Look AHEAD) study and followed up to 7/8 years. In Aim 1, we will test the hypothesis that baseline targeted metabolomics signatures, including amino acids and their metabolites, can predict successful long term surgical weight loss. In Aim 2, we will test the hypothesis that baseline metabolomics signatures will show incremental risk predictive capability for T2DM remission at 3 and 7 years, above and beyond well-known clinical predictors. In both aims, we will test the hypothesis that the change of the metabolomic signature will differ between types of intervention, at matched weight loss. This will help identif mechanisms of the superior effect of GBP, independent of weight loss. Both targeted (Aims 1 and 2) and non-targeted (Aim 3) mass spectrometry-based metabolomics and pathway analysis will be performed. Results from this award would support a more personalized approach for the surgical treatment of obesity and T2DM, based on a model integrating patient clinical factors and metabolite levels measured prior to weight loss intervention, rather than simply on BMI and surgeons' preference. Moreover, our data will help uncover novel pathways related to the mechanisms of the effect of GBP, independent of weight loss.

 描述（由适用提供）：减肥手术对体重减轻和代谢益处的可持续性在手术类型和个人之间是高度可变的。此外，与限制性程序相比，胃旁路（GBP）的优势作用的机制尚不清楚。我们的具体目标是：1）确定减肥手术后长期体重减轻和代谢改善的生物标志物预测因素； 2）为了确定GBP和可调胃带（LAGB）执行其效果的不同机制，即表征GBP与LAGB的上代谢作用的基础机制。为了实现这些目标，我们将对从特征良好的患者收集的样本进行代谢组分析，这些患者经历了GBP和LAGB，并随后在对减肥手术的纵向评估（LABS）研究中最多随后进行了7年的研究，并将与他们与T2DM的非操作对照进行比较，并与最初的BMI匹配（从WhoSeles中匹配），该动作是从WhoSeles中进行的，该动作是一定的。 （向前看）研究并随后最多7/8年。在AIM 1中，我们将检验以下假设：基线靶向代谢组学特征（包括氨基酸及其代谢产物）可以预测成功的长期手术体重减轻。在AIM 2中，我们将检验以下假设：基线代谢组学特征将显示出3和7年在3年和7年中的T2DM缓解能力的增量风险预测能力，超过了众所周知的临床预测因子。在这两个目标中，我们都将检验以下假设：在匹配的体重减轻时，干预类型之间的代谢组签名的变化将有所不同。这将有助于确定与体重减轻无关的GBP效果的机制。将进行基于质谱的代谢组学和非靶向（目标3）的目标（目标1和2）和途径分析。该奖项的结果将基于整合患者临床因素和体重减轻干预之前测量的患者临床因素和代谢水平的模型，支持对肥胖和T2DM的手术治疗的更个性化的方法，而不是简单地基于BMI和外科医生的偏好。此外，我们的数据将有助于发现与重量减肥无关的GBP效果机制相关的新型途径。