Effect of GLP-1 on Microvascular Insulin Responses in Type 1 Diabetes
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- change in insulin sensitivity between baseline and 2 hour insulin clamp
研究概览
简要总结
GLP-1 increases skeletal and cardiac microvascular perfusion and improves insulin's microvascular responses in human subjects with T1DM, leading to improved metabolic insulin responses, endothelial function, and increased muscle oxygenation
详细描述
The proposed study will determine the effect of GLP-1 infusion on microvascular perfusion and microvascular insulin responses in both skeletal and cardiac muscle microvasculature in humans with T1DM. The investigators will study 20 participants with T1DM using a state-of-the-art technology, contrast enhanced ultrasound (CEU), to assess whether GLP-1 augments skeletal and cardiac microvascular blood flow (MBF) as a representation of microvascular perfusion, flow-mediated dilation (FMD) as a measurement of endothelial function, and augmentation index (AI) and pulse wave velocity (PWV) as surrogates for large vessel compliance. The investigators will use the combined CEU and euglycemic-hyperinsulinemic clamp approach to determine if microvascular and metabolic IR improves as a result.
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 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •History of type 1 diabetes, duration > 1 year
- •Age 18-40 years
- •HbA1c < 8.5%
- •BMI >/=18, <30 kg/m2
- •Using insulin for diabetes treatment only
- •On stable regimen of non-diabetic medications for the last 6 months, excluding oral contraceptives (OCP)
- •All screening labs within normal limits or not clinical significant
排除标准
- •Pregnancy or currently breastfeeding 2) Smoking history within 6 months 3) History of microvascular (microalbuminuria, retinopathy, neuropathy) or macrovascular diabetes complications (coronary artery disease, stroke, peripheral vascular disease) 4) Taking vasoactive medications (i.e. calcium channel blockers, angiotensin-converting enzyme or renin inhibitors, angiotensin-receptor blockers, nitrates, alpha-blockers) 5) OCP use within 3 months or 1 month if menses has subsequently occurred 6) Known hypersensitivity to perflutren (contained in Definity© contrast) 7) Screening O2 saturation<90% 8) Anemia (hemoglobin <12 g/dL in women, hemoglobin <13 g/dL in men) 9) Diabetic ketoacidosis (DKA) on presentation to screening visits or study admission days
研究组 & 干预措施
GLP-1 + Insulin clamp
GLP-1 infusion 1.2 pmol/kg/min for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min
干预措施: Insulin (Drug)
GLP-1 + Insulin clamp
GLP-1 infusion 1.2 pmol/kg/min for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min
干预措施: Dextrose 20 % in Water (Drug)
Saline + Insulin clamp
Saline infusion at 30 ml/hr for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min.
干预措施: Insulin (Drug)
Saline + Insulin clamp
Saline infusion at 30 ml/hr for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min.
干预措施: Dextrose 20 % in Water (Drug)
GLP-1
GLP-1 infusion 1.2 pmol/kg/min for 150 min
干预措施: GLP-1 (Drug)
GLP-1 + Insulin clamp
GLP-1 infusion 1.2 pmol/kg/min for 150 min and insulin 1 mU/kg/min + Dextrose 20% at variable rate to maintain euglycemia for 120 min
干预措施: GLP-1 (Drug)
结局指标
主要结局
change in insulin sensitivity between baseline and 2 hour insulin clamp
时间窗: baseline and after 2 hour insulin clamp
vascular measurement
change in microvascular blood volume between baseline and 2 hour insulin clamp
时间窗: baseline and after 2 hour insulin clamp
vascular measurement
次要结局
- change in augmentation index between baseline and 2 hour insulin clamp(baseline and after 2 hour insulin clamp)
- change in flow-mediated dilation between baseline and 2 hour insulin clamp(baseline and after 2 hour insulin clamp)
- change in pulse wave velocity between baseline and 2 hour insulin clamp(baseline and after 2 hour insulin clamp)
研究者
Zhenqi Liu
Deparment of Medicine, Chief of Div. Endocrinology, University of Virginia
University of Virginia