Free Fatty Acids-Induced Hypertension and Endothelial Dysfunction in Obese Subjects
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Change in Systolic Blood Pressure From Baseline to After Completing an Oral 32-gram Fat Load in Obese Normotensive Subjects.
研究概览
简要总结
The study is a prospective open label study to examine the effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects. Subjects will receive either 8-hour of intravenous or oral fat loads in either low or high doses or normal saline in random order. Blood samples are drawn and vitals are measured before and after the infusions. Endothelial function and plasma glucose and lipid levels are measured to study the effects.
详细描述
Insulin resistance has been implicated as the central mechanism in the development of several cardiovascular risk factors including hypertension, diabetes, lipid disorders, and coagulation disorders. Recent evidence suggests that increased levels of a circulation fat (free fatty acids or FFAs) are a leading candidate causing insulin resistance. Our preliminary studies in indicate that, in addition to insulin resistance, the infusion of Intralipid and heparin to increase FFAs resulted in a significant rise in systolic and diastolic blood pressure, impaired endothelial (vascular) function, and increased inflammatory markers in obese African Americans with and without diabetes. The effects of FFA on insulin action are well established; however, the blood pressure and vascular effects of FFAs infusion in obese subjects have not been fully investigated. We hypothesize that observed changes in blood pressure are the result of acute endothelial dysfunction, and/or increased activation of the autonomic nervous system. No previous studies have attempted to determine a dose response effect of increasing FFA on blood pressure. In addition, it is not know if increased FFAs by repeated oral fat load results in similar blood pressure than intravenous lipid infusion. Accordingly, we propose: 1) a systematic evaluation of the effects of increasing FFA levels on blood pressure and endothelial (vascular) function, and 2) determine the effects of comparable increases in FFA concentration via intravenous infusion of Intralipid or by repeated oral fat load on blood pressure, insulin resistance and endothelial dysfunction in obese subjects.
A group of obese normotensive subjects will be admitted to the Grady Clinical Research Center or to the Outpatient Research Unit in the Grady Diabetes Clinic on five occasions. In four of these admissions, research subjects will receive an 8-hour intravenous infusion, in random order, of increasing Intralipid concentration (10 ml, 20 ml, 40 ml per hour) or normal saline (40 ml per hour). During the final admission, research subjects will receive an oral liquid fat diet every 2 hours for 8-hours. The effect of increased FFAs on blood pressure and endothelial (vascular) function via intravenous infusion and via oral fat load therapy will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 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
- •Males or females between the ages of 18 and 65 years.
- •Definition: obese = BMI ≥ 30 kg/m2
- •Blood pressure < 140/80 mm Hg and no prior history of hypertension
排除标准
- •History of hypertension or previous history of antihypertensive drug therapy.
- •Current tobacco use
- •Fasting triglyceride levels > 250 mg/dL during the stabilization period.
- •Liver disease (ALT 2.5x > upper limit of normal), or other significant medical or surgical illness, including myocardial ischemia, congestive heart failure, liver failure, and infectious processes.
- •Serum creatinine ≥1.5 mg/dL for males, or ≥ 1.4 mg/dL for females.
- •History of drug or alcohol abuse within the last 5 years.
- •Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
- •Female subjects are pregnant or breast feeding at time of enrollment into the study.
研究组 & 干预措施
Intralipid 20%@ 20cc/hour
Intralipid 20% IV infusion at 20cc/hour
干预措施: Intralipid 20% @ 20cc/hour (Drug)
Intralipid 20% @ 40cc/hour
Intralipid 20% IV infusion at 40cc/hour
干预措施: Intralipid 20%@ 40cc/hour (Drug)
Normal Saline infusion @ 40cc/hour
Normal Saline continuous IV infusion at 40cc/hour for 8 hours
干预措施: Normal Saline (Drug)
32-gram oral fat load
32-gram oral fat load once
干预措施: 32-gram oral fat load (Dietary Supplement)
64-gram oral fat load
64-gram oral fat load once
干预措施: 64-gram oral fat load (Dietary Supplement)
结局指标
主要结局
Change in Systolic Blood Pressure From Baseline to After Completing an Oral 32-gram Fat Load in Obese Normotensive Subjects.
时间窗: Baseline and at the end of the 8-hours
To study the effects of oral low dose fat load on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on admission when patient was in Supine position.The Blood pressure was measured at admission and at end of the fat load. The BP from the admission are compared to BP after the fat load. A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.
Change in Systolic Blood Pressure to After Completing an 8-hour Normal Saline Infusion in Obese Normotensive Subjects.
时间窗: Baseline and at the end of the 8-hours
To study the effects of high dose oral fat load on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on admission when patient was in Supine position. The Blood pressure was measured at admission and at end of the fat load. The BP from the admission are compared to BP after the fat load. A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.
Change in Systolic Blood Pressure From Baseline to After Completing an 8-hour 20% Intralipid @ 20cc/hr Infusion in Obese Normotensive Subjects.
时间窗: Baseline and at the end of the 8-hours
To study the effects of low dose intravenous (IV) fat infusion on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on admission when patient was in Supine position. The Blood pressure was measured at admission and at every 2 hours till the end of infusion. The BP from the admission are compared to BP after the infusion.A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.
Changes in Systolic Blood Pressure From Baseline to After Completing an 8-hour 20% Intralipid @ 40cc/hr Infusion in Obese Normotensive Subjects
时间窗: Baseline and at the end of the 8-hours
To study the effects of high dose intravenous (IV) fat infusion on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on admission when patient was in Supine position. The Blood pressure was measured at admission and at every 2 hours till the end of infusion. The BP from the admission are compared to BP after the infusion. A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.
Changes in Systolic Blood Pressure From Baseline to After Completing an Oral 64-gram Fat Load in Obese Normotensive Subjects
时间窗: at the end of the 8 hours
To study the effects of high dose oral fat load on systolic blood pressure (SBP) in healthy obese subjects, subject's baseline SBP is compared to SBP after the infusion. Blood Pressure (BP) was measured with a manual cuff in triplicate on admission when patient was in Supine position. The Blood pressure was measured at admission and at end of the fat load. The BP from the admission are compared to BP after the fat load. A normal systolic blood pressure is lower than 120 mmHg; elevated blood pressure if the systolic reading is 120-129 mmHg. A level above 140 mmHg is considered hypertension.
次要结局
- Change in Flow-mediated Dilation (FMD) of Endothelium-dependent Brachial Artery From Baseline to After Completing a Specific Intervention in Obese Normotensive Subjects.(Baseline and at the end of the 8-hours)
- Change in C-peptide Concentration Levels From Baseline to After Specific Intervention Among the Healthy Obese Subjects(baseline and after 8 hours after admission)
- Change in Blood Glucose Levels From Baseline to 6-8 Hours After Intervention Among Obese Healthy Subjects(Baseline and at the end of the 8-hours)
- Change in Blood Insulin Levels From Baseline to After Intervention Among the Normal Obese Subjects(Baseline and at the end of the 8-hours)
研究者
Guillermo Umpierrez, MD
Professor of Medicine
Emory University