Metabolomic Biomarkers Predictors of Long-term Success Following Bariatric surgery

 描述(由申请人提供)：减肥手术在减肥和代谢益处方面的可持续性在手术类型和个人之间存在很大差异。此外，胃旁路手术(GBP)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指标；2)确定GBP和可调节胃束带(LAGB)发挥作用的不同机制，即表征GBP和LAGB优越的代谢效应的机制。为了实现这些目标，我们将对从经过GBP和LAGB并在减肥手术纵向评估(LABS)研究中随访长达7年的特征良好的患者收集的样本应用代谢组学分析，并将他们与T2 DM的非手术对照组进行比较，这些对照组的初始BMI匹配，后者参与了糖尿病健康行动(Look Ahead)研究的生活方式干预(LSI)，并进行了长达7/8年的随访。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，我们将测试这样一个假设，即基线代谢组学特征将在3年和7年内显示出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指标。在这两个目标中，我们将检验这样一个假设，即不同类型的干预措施在匹配的体重减轻时代谢特征的变化会有所不同。这将有助于确定GBP的优越效果的机制，独立于体重减轻。将进行靶向(目标1和目标2)和非目标(目标3)基于代谢组学和途径分析的代谢组学和途径分析。这一奖项的结果将支持一种更个性化的手术治疗肥胖症和2型糖尿病的方法，该方法基于一个模型，该模型集成了患者的临床因素和在减肥干预之前测量的代谢物水平，而不是简单地根据BMI和外科医生的偏好。此外，我们的数据将有助于揭示与GBP效果机制相关的新途径，而不是与减肥无关。

 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.