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: 9280932
• 负责人: BLANDINE B LAFERRERE
• 金额: $ 50.1万
• 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/9280932
• 关键词: Amino Acids; Award; Behavioral; Beta Cell; Bile Acids; Bile fluid; Biochemical Pathway; Biological; 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; Elements; Failure; Gastric Bypass; Goals; Health; Health Personnel; Heterogeneity; 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; Patient Care; 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; outcome prediction; personalized approach; predictive marker; predictive modeling; preference; public health relevance; 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（由申请人提供）：减肥手术对减肥和代谢益处的可持续性在手术类型和个体之间存在很大差异。此外，胃旁路术（GBP）的上级效果优于限制性手术的机制尚不清楚。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子;以及2）确定GBP和可调节胃束带（LAGB）发挥其作用的不同机制，即表征GBP相对于LAGB的上级代谢作用的机制。为了实现这些目标，我们将代谢组学分析应用于从接受了GBP和LAGB并在减肥手术纵向评估（LABS）研究中随访长达7年的充分表征的患者中收集的样本，并将其与初始BMI匹配的T2 DM非手术对照进行比较，他们参加了糖尿病健康行动（Look AHEAD）研究中的生活方式干预（LSI），并随访了7/8年。在目标1中，我们将测试基线靶向代谢组学特征（包括氨基酸及其代谢物）可以预测成功的长期手术减肥的假设。在目标2中，我们将检验以下假设：基线代谢组学特征将显示3年和7年时T2 DM缓解的增量风险预测能力，高于和超过众所周知的临床预测因素。在这两个目标中，我们将测试代谢组学特征的变化在匹配的体重减轻时在干预类型之间会有所不同的假设。这将有助于确定GBP的上级作用的机制，而与体重减轻无关。将进行靶向（目标1和2）和非靶向（目标3）基于质谱的代谢组学和途径分析。该奖项的结果将支持肥胖和T2 DM手术治疗的更个性化方法，该方法基于整合患者临床因素和减肥干预前测量的代谢物水平的模型，而不仅仅是BMI和外科医生的偏好。此外，我们的数据将有助于发现与GBP作用机制相关的新途径，而与体重减轻无关。