WHAT ARE THE UNIQUE BENEFITS OF PIOGLITAZONE COMPARED TO WEIGHT LOSS

与减肥相比，吡格列酮有哪些独特的好处

• 批准号: 7717883
• 负责人: TRACEY MCLAUGHLIN
• 金额: $ 5.78万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717883
• 关键词: Abdomen; Adipocytes; Adipose tissue; Adult; Age; Anemia; Biopsy; Blood; Blood Pressure; Blood Tests; Body Weight decreased; Cardiovascular Diseases; Catheters; Computer Retrieval of Information on Scientific Projects Database; Daily; Defect; Diabetes Mellitus; Dietitian; Dose; Equipment; Experimental Designs; Fasting; Fatty acid glycerol esters; Funding; Glucose; Grant; Heart Rate; Height; Hematocrit procedure; High Prevalence; Hour; Image; Individual; Institution; Insulin; Insulin Resistance; Intervention; Link; Lipids; Lipoproteins; Liver; Local anesthesia; Measures; Mediating; Medical History; Nonesterified Fatty Acids; Obesity; Overweight; Participant; Patients; Physiological; Pioglitazone; Qualifying; Randomized; Renal function; Research; Research Personnel; Resources; Risk; Sampling; Screening procedure; Source; Subgroup; Surgical incisions; Testing; Time; Time Study; Ultrasonography; Umbilicus; United States National Institutes of Health; Upper arm; Vasodilation; Visceral; Visit; Week; Weight; Weights and Measures; X-Ray Computed Tomography; adipocyte differentiation; base; brachial artery; day; experience; glucose uptake; improved functioning; insulin sensitivity; liver function; programs; scalpel; subcutaneous; weight loss intervention

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypotheses: 1. A defect in adipocyte differentiation in the setting of caloric excess/obesity is responsible for the variability in insulin-mediated glucose uptake (IMGU) observed in overweight/obese individuals. 2. The insulin-resistant (IR) subgroup of obese individuals will demonstrate abnormalities in adipocyte differentiation/terminal function that improve in association with insulin sensitization via interventions targeting adipose tissue, but these changes will not be seen in insulin-sensitive controls who experience no change in insulin sensitivity with the same interventions. IR, present in 25-50% of US adults, increases the risk for diabetes mellitus by up to 24-fold, and cardiovascular disease (CVD) by up to 4-fold. A major contributor to the high prevalence of IR is increasing obesity among US adults. While body mass is positively correlated with IR, the physiologic mechanism linking adiposity to IR is not understood. For example, not all obese individuals are IR, nor are all lean individuals insulin-sensitive (IS). Experimental Design: The first visit (screening) will be to determine if a patient qualifies for the study based on age, height, weight, and medical history. Participants will have height, weight measured and blood pressure and heart rate taken and a lab test to check glucose level and hematocrit (to check for anemia). The second visit will be the insulin sensitivity test. This test will determine if a patient qualifies to participate in this study. At this time lipid levels as well as liver and kidney function will be measured. Those who are IR or IS will qualify for the study. This test will be repeated at the end of the study for the qualifying participants. For those who qualify, an eight-hour meal profile will be done on another day. After an overnight fast (12-14 hrs) an IV catheter will be placed in one arm for blood draws. After the fasting sample is drawn the patient will receive a standardized breakfast and four hours later lunch. Blood draws will be once/hr for 8 hrs for insulin, glucose, free fatty acid (FFA), and lipoproteins among other things related to IR. A separate blood test for a lipid profile will be done at the time of the meal profile. This test will be repeated at the end of the study. For those who qualify, a fat cell biopsy will be done at the beginning and end of the study. After the induction of local anesthesia, a 1-cm incision will be made with a scalpel in the peri-umbilical region, and approximately 1-2 g of superficial subcutaneous adipose tissue will be removed. For those who qualify, a single picture, cross-sectional CT scan of the abdomen at the level of the umbilicus, will be done before and at the end of the study to quantify subcutaneous (SC) versus visceral distribution of fat before and after intervention. Brachial Artery Vasodilation test may be done before and after the study if equipment is available to us at the time of this study. This is a noninvasive test using an ultrasound probe used to image the brachial artery. Once all baseline studies are complete the study participant will be randomized to receive either a weight-loss program or started on Pioglitazone. If started on Pioglitazone the starting dose will be 30 mg daily for one month and then the dose will be increased to 45 mg daily for the remainder of the study (2 more months) Once intervention is started the participant will come in to the GCRC every two weeks for three months, or more frequently if needed, to have their weight and blood pressure measured, and be seen by one of Dr. Reaven's associates. If they are in the weight loss intervention they will also meet with the research dietitian. A lab test to measure liver function (ALT) will be done once per month.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 假设： 1。脂肪细胞分化的缺陷在过量/肥胖的情况下是导致超重/肥胖个体中观察到的胰岛素介导的葡萄糖摄取（IMGU）的可变性。 2。肥胖个体的胰岛素耐药（IR）亚组将证明脂肪细胞分化/末端功能的异常，通过靶向脂肪组织的干预措施与胰岛素敏化相关，但这些变化将在胰岛素敏感的对照中不会出现在胰岛素敏感性方面没有变化的胰岛素敏感对照中，而这些变化将不会出现。 IR（美国成年人中有25-50％）将糖尿病的风险提高了24倍，心血管疾病（CVD）最多增加了4倍。 IR的高流行率的主要因素是美国成年人的肥胖症增加。尽管体重与IR呈正相关，但尚不清楚将肥胖与IR联系起来的生理机制。例如，并非所有肥胖个体都是IR，也不是所有瘦人对胰岛素敏感的人（IS）。 实验设计： 第一次访问（筛查）将是确定患者是否根据年龄，身高，体重和病史符合研究的资格。参与者将具有高度，体重测量，血压和心脏速度以及实验室测试以检查葡萄糖水平和血细胞比容（检查贫血）。 第二次访问将是胰岛素敏感性测试。该测试将确定患者是否有资格参加这项研究。目前将测量脂质水平以及肝脏和肾功能。那些IR或IR的人将有资格参加该研究。该测试将在研究结束时为合格参与者重复。 对于那些有资格的人，将在另一天完成八个小时的餐食。过夜快速（12-14小时）后，将把IV导管放在一只手臂中进行抽血。抽出禁食样品后，患者将获得标准化的早餐和四个小时后的午餐。吸血将是一次/小时，持续8小时，用于胰岛素，葡萄糖，游离脂肪酸（FFA）和脂蛋白，以及与IR相关的其他因素。在进餐时，将对脂质剖面进行单独的血液检查。该测试将在研究结束时重复。 对于那些有资格的人，将在研究的开始和结束时进行脂肪细胞活检。诱导局部麻醉后，将用手术刀在野蛮区域进行1 cm切口，并将去除大约1-2 g的1-2 g浅表皮下脂肪组织。 对于那些符合条件的人，将在研究结束前后进行一张腹部腹部的横截面CT扫描，以量化干预前后脂肪的皮下（SC）与脂肪的内脏分布。 如果在本研究时我们可以使用设备，则可以在研究之前和之后进行臂动脉血管舒张测试。这是使用用于对臂动脉成像的超声探针的无创测。 一旦所有基线研究完成，研究参与者将被随机分配以接受减肥计划或开始于吡格列酮。如果开始使用Pioglitazone，则开始剂量每天30毫克持续一个月，然后在剩余的研究中（又2个月），剂量将增加到45毫克，一旦开始干预，参与者将每两个月进入GCRC，或者在需要的情况下每两个月进入GCRC，如果需要的（如果需要），则可以根据自己的体重和血压测量，并通过一家人来看，并可以看到。如果他们处于减肥干预措施中，他们还将与研究营养师会面。测量肝功能（ALT）的实验室测试将每月进行一次。