A Randomized, Crossover Study to Evaluate the Effect of Lipid Infusion on TLR4 Signaling and Insulin Resistance in Human Muscle
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Muscle Insulin Sensitivity-M Value
研究概览
简要总结
The purpose of this study is to determine whether a lipid infusion can up-regulate toll-like receptor 4 (TLR4) signaling in human subjects
详细描述
The investigators plan to examine the effect of a lipid infusion on TLR4 expression and insulin sensitivity. A group of 30 subjects aged 18-60 years old, lean (BMI < 26 kg/m2) normal glucose tolerant subjects without a family history of type 2 diabetes will receive a lipid or saline infusion. The subjects will be randomly assigned to first receive either a 48 hour long lipid or saline infusion. Approximately 4-6 weeks later subjects will return to undergo another study (if, in the first study they received lipid, on the second study they will receive saline, and vice versa). A near-equal number of women and men will be included in each group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects must have the following laboratory values: Hematocrit ≥ 35%, serum creatinine ≤ 1.5 mg/dl, aspartate aminotransferase (AST) < 2 X upper limit of normal, Alanine aminotransferase (ALT) < 2 X upper limit of normal, alkaline phosphatase < 2 X upper limit of normal, normal urinalysis [no glucose, trace protein, trace ketones, lipase < 50 IU/L, no bacteria, up to 1-3 white blood cells (WBC) and red blood cells (RBC) per hpf], and normal platelets, prothrombin time (PT) and partial thromboplastin time (PTT).
- •Female subjects must be non-lactating. Female patients are eligible only if they have a negative pregnancy test throughout the study period (or postmenopausal). Postmenopausal women taking hormone replacement will be included if they have been on a stable dose for ≥6 months.
- •Subjects whose body weight has been stable (within 2%) for at least three months.
排除标准
- •Subjects with impaired glucose tolerance based on American Diabetes Association criteria.
- •Subjects taking drugs known to affect glucose and lipid homeostasis will be excluded. Statins will be permitted if the subject has been on a stable dose for at least three months. Subjects who have taken for more than a week non-steroidal anti inflammatory drugs (NSAIDS) within two months or systemic steroids, anabolic steroids, growth hormone or immunosuppressants within 12 months will be excluded. Subjects taking low-dose (81 mg/day or less) aspirin will be allowed.
- •Patients with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
- •Recent systemic or pulmonary embolus, impaired renal function, poorly controlled blood pressure (systolic BP>170, diastolic BP>95), resting heart rate >100, electrolyte abnormalities, neuromuscular or musculoskeletal disease.
- •Subjects who smoke.
- •Subjects who engage in a regular exercise program (zero or one exercise sessions per week are allowed).
- •Any subject who has donated blood in the previous two months.
- •Any subject with a hematocrit of less than
- •Subjects who are claustrophobic.
- •Women taking oral contraceptives.
- •alcohol consumption greater than 30 grams daily.
- •baseline plasma triglyceride levels over 200 mg/dl
研究组 & 干预措施
Intralipid 20%, then saline
Participants first received lipid infusion of 30ml/h x48h. After a washout period of 4-6 weeks, they then received saline infusion of 30ml/h x48h.
干预措施: Intralipid 20% (Drug)
Intralipid 20%, then saline
Participants first received lipid infusion of 30ml/h x48h. After a washout period of 4-6 weeks, they then received saline infusion of 30ml/h x48h.
干预措施: Saline (Drug)
Saline, then Intralipid
Participants first received saline infusion of 30ml/h x48h. After a washout period of 4-6 weeks, they then received lipid infusion of 30ml/h x48h.
干预措施: Intralipid 20% (Drug)
Saline, then Intralipid
Participants first received saline infusion of 30ml/h x48h. After a washout period of 4-6 weeks, they then received lipid infusion of 30ml/h x48h.
干预措施: Saline (Drug)
结局指标
主要结局
Muscle Insulin Sensitivity-M Value
时间窗: 48 hr after lipid/saline infusion
Forty eight hrs after lipid or saline infusion, muscle insulin sensitivity will be measured by insulin clamp. The results are compared to determine whether lipid infusion reduces muscle insulin sensitivity compared to saline infusion.. The M value is defined as the exogenous glucose infusion rate at steady state (i.e, when the exogenous glucose infusion rate is equal to the rate of whole body glucose disposal).
次要结局
- Extracellular Signal-regulated Kinase (ERK) Phosphorylation in Muscle(48 hr following lipid or saline infusion, pre-clamp)
- TLR4 Messenger Ribonucleic Acid (mRNA) in Muscle(48 hr following lipid/saline infusion, pre-clamp)
研究者
Nicolas Musi, MD
Professor Diabetes Division
The University of Texas Health Science Center at San Antonio