Effects of PPAR Ligands on Ectopic Fat Accumulation and Inflammation in Subjects With Impaired Glucose Tolerance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Insulin Sensitivity
研究概览
简要总结
The relationship between obesity and insulin resistance is known, however the mechanism(s) associating obesity with insulin resistance is not well understood. Inflammation and accumulation of fat in non fat tissue (like muscle) are conditions found on obesity which could be the potential link between obesity and insulin resistance. This study is designed to test the effects of two different drugs on numerous features of the obesity and insulin resistance in subjects with impaired glucose tolerance. Impaired glucose tolerance is a condition where blood sugar is too high after drinking a sugary drink containing 75 grams of sugar. Impaired glucose tolerant subjects are insulin resistant and at risk of developing diabetes. The drugs to be used are fenofibrate and pioglitazone. Fenofibrate is used to reduce the amount of fat (triglycerides) in the blood while pioglitazone is routinely used to make the body more sensitive to insulin in patients with diabetes. The purpose of this study is to compare the effects of either of these two medications (pioglitazone and fenofibrate) alone or the combination of both on fat accumulation in body (muscle) and inflammation. The amount of fat accumulation in muscle is thought to affect insulin sensitivity. In addition, the changes in the level of proteins produced by fat tissues will be studied in response to the two medications in this study. These proteins are thought to be involved in diabetes and insulin resistance.
These studies are designed to examine fundamental clinical mechanisms underlying the metabolic syndrome and diabetes.
详细描述
The correlation between obesity, inflammation and ectopic fat accumulation is well recognized; however, the mechanism(s) responsible for obesity induced insulin resistance is not well understood. The investigators will focus on lipotoxicity and inflammation as the link between obesity and insulin resistance. The factors leading to inflammation and ectopic lipid accumulation in obesity and the best intervention to reverse this pathophysiology are not clear. In this study, the investigators will examine inflammation in adipose tissue and muscle lipid mechanism in response to Peroxisome Proliferator Activated Receptors (PPAR) and ligands have synergistic anti-inflammatory effects in adipose tissue and activation of PPAR and decrease muscle lipid oxidation and redistribution of lipid from muscle to adipocytes respectively. The combination of both medications will be particularly effective in reducing inflammation and muscle lipid accumulation.
In this study, IGT subjects will be randomized to treatment with PPAR ligand (fenofibrate), PPAR ligand (pioglitazone) or combination of both for 10 weeks. Baseline studies will include assessment of body composition, insulin sensitivity, muscle and fat biopsies. All studies will be repeated after treatment with fenofibrate, pioglitazone or combination of both.
Specific Aims (SA) are as follows:
SA 1. Insulin sensitivity and Intramyocellular lipid (IMCL) from muscle biopsy specimens will be measured in response to different treatments (PPAR , and combination of both ligands).
SA 2. The rate of fatty acid oxidation and the number of mitochondria in muscle will be measured in response to PPAR ligands.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Impaired glucose tolerance and/or impaired fasting glucose and/or metabolic syndrome
- •Age 18-65
- •BMI 28-38
排除标准
- •Renal insufficiency: creatinine.1.4
- •Liver disease: ALT.2x normal, congestive heart failure, history of documented coronary artery disease, concomitant use HMG CoA-reductase inhibitors (statins)
- •Concurrent use of ASA, steroids and other anti-inflammatory agents
研究组 & 干预措施
Fenofibrate 145 mg PO QD and Pioglitazone 45 mg PO QD
Treatment with pioglitazone and fenofibrate in subjects with pre diabetes
干预措施: Fenofibrate 145mg PO QD (Drug)
Fenofibrate 145 mg PO QD and Pioglitazone 45 mg PO QD
Treatment with pioglitazone and fenofibrate in subjects with pre diabetes
干预措施: Pioglitazone 45 mg PO QD (Drug)
Fenofibrate 145 mg PO QD
Treatment with fenofibrate in subjects with pre diabetes
干预措施: Fenofibrate 145mg PO QD (Drug)
结局指标
主要结局
Insulin Sensitivity
时间窗: 3 months
Insulin sensitivity was measure through frequently sampled intravenous glucose tolerance test. Subjects presented to research center fasting. Blood samples were collected at -21, -11, and -1 minutes. At time t=0 initiates the start of the IVGTT and the injection of glucose into the non-sampling arm. The glucose dose was calculated as 11.4g/m2 of body surface area, given as a 50% dextrose solution. This glucose injection was administered over 60 seconds or less. At time t=20 minutes, an insulin dose of 0.04u/kg was administered over 30 seconds. Blood samples were collected at times t=2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 70, 90, 100, 120, 140, 160, and 180. If blood sugar did not return to a steady state the test was continued to t= 210 or t= 240.
次要结局
- IMCL(3 months)