BARIATRIC SURGERY CLINICAL RESEARCH CONSORTIUM

描述（由申请人提供）： 肥胖症研究的主要目的是将肥胖症的病理生理学定义为预防和/或有效治疗该疾病的基础。涉及减肥手术患者的研究领域可能包括：1）确定最佳手术方法，2）确定影响合并症发展和手术结局的生物学和遗传学差异，3）利用该人群作为研究肥胖症发病机制和治疗反应的模型。我们建议肥胖研究临床研究联盟（BSCRC）采用一个全面的关系数据库，其中包括所有临床中心（CC）容易获得的参数，如基本人体测量学，身体成分的测量，临床和手术史，以及定量合并症量表的记录。该量表对17种与肥胖相关的合并症（包括糖尿病、高血压和高脂血症）进行评分，并将治疗作为症状严重程度的衡量标准。BSCRC参与者可能需要进一步完善comorbance量表分级。该量表将使合并症与mRNA表达谱和内分泌反应相关。 加州大学戴维斯分校提出了两个具体的协议，由BSCRC进行。短期方案将使用定量PCR测量手术时减肥手术患者的皮下和网膜脂肪、肝脏和肠中肥胖相关基因的mRNA表达水平。身体组成的措施，包括身体脂肪的分布，内分泌反应胃旁路术，和临床合并症评分将允许从手术时间到术后2年的时间点的受试者的详细表型。这将是一个重要的第一步，了解类似肥胖症的受试者之间的合并症发生的变化。长期方案将是一项3-5年的纵向研究，研究胃旁路手术对激素活性、身体成分和体力活动的反应。在这个阶段，与短期研究中得出的术前遗传和内分泌标志物以及合并症评分的相关性将确定哪些患者最受益于胃旁路术。BSCRC积累的这一数据和其他数据将为建立肥胖合并症及其对手术治疗反应的进一步研究提供基础。

DESCRIPTION (provided by applicant): A primary objective of obesity research is to define the pathophysiology of obesity as a basis for preventing and/or effectively treating the disease. The areas for research involving bariatric surgery patients may include: 1) defining optimal surgical approaches, 2) identification of biological and genetic differences that influence development of comorbidities and outcomes of surgery, and 3) utilizing this population as a model for study of the pathogenesis and response to treatment of obesity. We propose that the Bariatric Research Clinical Research Consortium (BSCRC) employ a comprehensive relational database that includes parameters readily available to all Clinical Centers (CCs), such as basic anthropometrics, measures of body composition, clinical and surgical history, and recording of a quantitative comorbidity scale. This scale scores each of 17 comorbidities related to obesity, including diabetes, hypertension, and hyperlipidemia, and utilizes treatment as a gauge for the severity of symptoms. Further refinement to the comorbidity scale grading may be required by BSCRC participants. This scale will enable comorbidities to be correlated with mRNA expression profiles and endocrine response. UC Davis proposes two specific protocols for conduct by the BSCRC. The short term protocol will measure, using quantitative PCR, the mRNA expression level of obesity related genes in the subcutaneous and omental fat, liver, and intestine of bariatric surgery patients at the time of operation. Measures of body composition including the distribution of body fat, endocrine response to gastric bypass, and the clinical comorbidity scores will allow detailed phenotyping of the subjects from the time of operation to timepoints 2 years post-op. This will be an important initial step towards understanding the variation of comorbidity occurrence between subjects of similar adiposity. The longer term protocol will be a 3-5 year longitudinal study of the response to gastric bypass in relation to hormone activity, body composition, and physical activity. At this phase, correlation with the preoperative genetic and endocrine markers derived in the short term study, as well as history of comorbidity scores, would identify those patients who would most benefit from gastric bypass. This and other data accumulated by the BSCRC will provide a basis for establishment of further studies of obesity comorbidities and their response to surgical treatment.