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: 7605230
• 负责人: TRACEY MCLAUGHLIN
• 金额: $ 19.37万
• 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: 2007-02-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605230
• 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 假设： 1. 热量过量/肥胖情况下脂肪细胞分化的缺陷是超重/肥胖个体中观察到的胰岛素介导的葡萄糖摄取（IMGU）变异的原因。 2. 肥胖个体的胰岛素抵抗 (IR) 亚组将表现出脂肪细胞分化/终末功能异常，通过针对脂肪组织的干预措施，脂肪细胞分化/终末功能会随着胰岛素敏感性的改善而改善，但这些变化不会在没有经历过胰岛素敏感性对照的胰岛素敏感对照中出现。通过相同的干预措施，胰岛素敏感性发生变化。 25-50% 的美国成年人患有 IR，可使患糖尿病的风险增加高达 24 倍，使患心血管疾病 (CVD) 的风险增加高达 4 倍。 IR 高患病率的一个主要原因是美国成年人肥胖率的增加。虽然体重与 IR 呈正相关，但将肥胖与 IR 联系起来的生理机制尚不清楚。例如，并非所有肥胖个体都是 IR，也不是所有瘦个体都对胰岛素敏感 (IS)。 实验设计： 第一次就诊（筛查）将根据年龄、身高、体重和病史确定患者是否有资格参加研究。参与者将测量身高、体重、血压和心率，并进行实验室测试以检查血糖水平和血细胞比容（以检查是否贫血）。 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。此时将测量血脂水平以及肝肾功能。那些属于 IR 或 IS 的人将有资格参加该研究。该测试将在研究结束时对合格的参与者重复进行。 对于符合资格的人，将在另一天进行八小时膳食分析。禁食过夜（12-14 小时）后，将在一只手臂上放置静脉导管进行抽血。抽取空腹样本后，患者将接受标准化早餐和四小时后的午餐。每小时抽血一次，持续 8 小时，检查胰岛素、葡萄糖、游离脂肪酸 (FFA) 和脂蛋白以及其他与 IR 相关的物质。进餐时将进行单独的血脂检测。该测试将在研究结束时重复进行。 对于符合资格的人，将在研究开始和结束时进行脂肪细胞活检。局部麻醉诱导后，用手术刀在脐周区域切开1厘米的切口，去除约1-2克浅层皮下脂肪组织。 对于符合条件的患者，将在研究之前和研究结束时对脐部水平的腹部进行单张图片横断面 CT 扫描，以量化干预前后的皮下 (SC) 与内脏脂肪分布。 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肱动脉血管舒张测试。这是一种无创测试，使用超声波探头对肱动脉进行成像。 一旦所有基线研究完成，研究参与者将被随机分配接受减肥计划或开始服用吡格列酮。如果开始使用吡格列酮，起始剂量将为每天 30 毫克，持续一个月，然后在研究的剩余时间（另外 2 个月），剂量将增加至每天 45 毫克。一旦开始干预，参与者将每隔三个月内，两周或更频繁地测量体重和血压，并由 Reaven 医生的一位同事进行检查。如果他们参与减肥干预，他们还将与研究营养师会面。每月进行一次测量肝功能 (ALT) 的实验室测试。