The Impact of Free Fatty Acid Reduction on Vascular Function and Skeletal Muscle Glucose Utilization in Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Flow-mediated Dilation After Placebo or Acipimox Treatment Between Healthy Controls and Those With Metabolic Syndrome
研究概览
简要总结
This study will test the hypothesis that reduction in release of free fatty acids from adipocytes will restore insulin-mediated endothelium-dependent vasodilation and skeletal muscle glucose metabolism in subject with type 2 diabetes.
详细描述
During the past two decades, there has been a steady increase in the incidence of diabetes mellitus, such that nearly 17 million people are now afflicted. The vast majority of these have type 2 diabetes. Over the next 40 years, the type 2 diabetic population in the United States is expected to increase to nearly 30 million.
Diabetes substantially increases the risk of atherosclerosis, and thereby, cardiovascular morbidity and mortality. Indeed, cardiovascular disease causes more than 50% of the mortality in patients with diabetes. People with type 2 diabetes manifest two cardinal signs of dysmetabolism: hyperglycemia and insulin resistance. Insulin resistance is a progressive phenomenon that occurs well before the onset of frank diabetes, and results in alterations in insulin signaling. Experimental studies suggest that insulin signaling is required for vascular homeostasis, and its impairment is associated with endothelial dysfunction. In the clinical setting, insulin resistance is associated with atherosclerosis and predicts cardiovascular events independent of hyperglycemia. Therefore, we will study the importance of insulin signaling in endothelial biology in humans and the effects of free fatty acids on endothelial function in people with type 2 diabetes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •type 2 diabetes mellitus (as defined by the National Diabetes Data Group)
- •normal cardiovascular exam
- •non smoker (for 1 year prior to entry)
- •Healthy volunteers
- •no known medical problems
- •normal cardiovascular exam
- •fasting glucose < 110 mg/dL
- •non-smoker (for 1 year prior to entry)
排除标准
- •Type 2 Diabetics
- •untreated hypertension (>140/90 mmHg)
- •untreated hypercholesterolemia (LDL > 75th percentile for age)
- •cigarette smoking within 1 year
- •neuropathy requiring medication
- •nephropathy (> 300mg/24 hour urinary albumin, or serum creatinine > 1.4 mg/dL
- •abnormal cardiovascular exam
- •treatment with thiazolidinedione within 1 year
- •post-menopausal women taking hormone replacement therapy
- •(Note: subjects taking angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) must stop these medications for 2 weeks prior to taking study drug. If blood pressure rises to >140/90, subjects will be prescribed an alternative medication or be withdrawn from the study.
- •Healthy Volunteers
- •abnormal cardiovascular exam
- •use of prescription medications
- •fasting glucose > 110mg/dL
- •cigarette smoking within 1 year
研究组 & 干预措施
2
placebo treatment for 7 days
干预措施: placebo (Drug)
1
Acipimox treatment for 7 days
干预措施: acipimox (Drug)
结局指标
主要结局
Flow-mediated Dilation After Placebo or Acipimox Treatment Between Healthy Controls and Those With Metabolic Syndrome
时间窗: 7 days
Flow mediated dilation is calculated as follows: A resting arterial diameter measurement is obtained using the average of 10 EKG-gated ultrasound images. Next, an occlusive pressure is applied (using a blood pressure cuff inflated to a suprasystolic pressure)for a period of 5 minutes. After 5 minutes, the cuff is rapidly deflated. This produces a reactive hyperemic response which is captured via ultrasound at 1 minute post cuff deflation (also 10 EKG-gated images averaged). The diameter of the artery following reactive hyperemia is calculated and compared to the resting diameter to obtain a percent dilation. This is flow-mediated dilation.
Difference in Insulin-mediated Skeletal Muscle Glucose Utilization Between Test Agent and Placebo
时间窗: baseline, 7 days
Insulin sensitivity (M) is measured by using a hyperinsulinaemic-euglycaemic clamp. Insulin sensitivity (M) was calculated as the average glucose infusion rate (mg/kg of body weight per min) over the last 30 min of the clamp. Higher values indicate better outcomes (more insulin sensitive), while lower values indicate more insulin resistance.
次要结局
未报告次要终点
研究者
Mark Alan Creager, MD
Associate Professor of Medicine, Harvard Medical School
Brigham and Women's Hospital