Natriuretic Peptides and Metabolic Risk in Obesity
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 主要终点
- Change in glycerol levels
研究概览
简要总结
The investigators are examining:
- the relationships of insulin levels and natriuretic peptide hormone levels, and
- the effects of administering an infusion of natriuretic peptide hormone on the breakdown of fat
in healthy lean and otherwise healthy obese individuals.
详细描述
The cardiac natriuretic peptide hormonal system may protect against the development of cardiometabolic risk. Epidemiologic studies have shown that in relatively healthy individuals without heart failure, low natriuretic peptide levels are associated with unfavorable cardiometabolic phenotypes, including higher blood pressure, obesity, higher insulin levels, and diabetes mellitus. Understanding the mechanisms behind the "natriuretic peptide deficiency" of obesity would illuminate an important way in which obesity interacts with the cardiovascular system.
The investigators propose a prospective cross-over design in 40 healthy lean and otherwise healthy obese individuals. The investigators propose the following specific aims and hypotheses:
Aim 1: To study the effect of hyperinsulinemia on the response of the natriuretic peptide system to salt loading.
Hypothesis 1: Hyperinsulinemia will suppress natriuretic peptide levels in both obese and lean individuals.
Aim 2: To examine the effect of an intravenous infusion of natriuretic peptide on acute markers of lipolysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women ages 18-50 years
- •BMI 18 to <25 kg/m2 (lean group, N=20) or BMI 30 to <40 kg/m2 (obese group, N=20)
排除标准
- •Current use of antihypertensive medications
- •Current use of glucocorticoids, metformin, or any antidiabetes medications
- •Prior or current cardiovascular disease, renal disease, or liver disease
- •Diabetes mellitus (taking insulin, other anti-diabetic agents, or diet-controlled)
- •Atrial fibrillation
- •Bleeding disorder or anemia
- •Elevated LFTs
- •estimuated GFR < 60 ml/min
- •Abnormal sodium or potassium level
- •Positive pregnancy test, women of child-bearing age not practicing birth control, women who are breastfeeding
研究组 & 干预措施
Saline Infusion
All subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide).
干预措施: Saline (Other)
Insulin Clamp
All subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide).
干预措施: Insulin (Drug)
BNP Infusion (Nesiritide)
All subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide).
干预措施: Nesiritide (Drug)
结局指标
主要结局
Change in glycerol levels
时间窗: 1 hour
Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion
Change in natriuretic peptide levels
时间窗: 4 hours (during 2-hour study infusions and for 2 hours after study infusions)
次要结局
- Change in energy expenditure assessed by indirect calorimetry(1 hour)
- Change in triglyceride levels(1 hour)
- Change in free fatty acid levels(1 hour)
研究者
Thomas Wang
Principal Investigator
Vanderbilt University Medical Center