Adverse Effects of Systemic Hypoglycemia Exposure on Endothelial Function in Humans
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Flow induced Dilation of the Brachial Artery (FMD%)
研究概览
简要总结
Prior work suggests exposure to low glucose levels (hypoglycemia) is associated with increased cardiovascular risk. However, whether there is a causal relationship between cardiovascular events and hypoglycemia remains unclear with conflicting data in the literature. In this study, we plan to study whether acute exposure of patients to clinically relevant (50-60 milligrams/deciliter) levels of hypoglycemia induces or worsens blood vessel endothelial dysfunction- a key 1st step in the development of heart attacks and strokes. This will be determined in humans both with and 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
- Other
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Type 2 Diabetes Inclusion Criteria
- •Adult age 21 or older
- •If on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase reductase therapy, must be on a stable dose for at least 6 weeks prior to enrollment
- •Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated hemoglobin greater than or equal to 6.5%.
- •Score of < 4 using the Gold method for assessing hypoglycemia awareness
- •Inclusion Criteria for Healthy subjects
- •Adult age 21 or older
- •No evidence of metabolic syndrome or diabetes, hypertension (BP≥140/90), or high cholesterol (LDL≥160) at the time of screen.
排除标准
- •History of stroke, peripheral arterial disease, or coronary artery disease (as defined by the presence of at least one coronary stenosis ≥ 40% on angiography or by confirmed history of myocardial infarction by standard criteria)
- •Evidence of other evident major illness including chronic renal insufficiency(plasma creatinine > 1.4 for women or 1.5 for men), liver disease (aspartate aminotransferase or alanine aminotransferase greater than 2.5 x normal), and cancer currently undergoing therapy or had therapy for cancer within 1 year of enrollment.
- •Pregnancy as determine by urinary pregnancy test
- •Subjects on warfarin, oral anti-thrombin inhibitors, or thienopyridines
- •Subjects who have had changes to dosing of thiazolidinedione, dipeptidyl peptidase-4 (DPP-4) inhibitor, or metformin therapy within 6 weeks of enrollment.
- •Failed Allen's test in both arms - unable to safely place an arterial line
- •Glucose reading of < 50 mg/dL and/or episodes of symptomatic hypoglycemia requiring the assistance of another person for recovery in the 2 years prior to enrollment.
- •History of hypoglycemic convulsions
- •Current fluoxetine therapy (known to interfere with neuroendocrine response to hypoglycemia)
- •Glycosylated hemoglobin over 8.5%
- •On aldosterone antagonist therapy at the time of enrollment
- •On insulin therapy at the time of screening.
- •History of allergy to local anesthetic injection like lidocaine.
- •Exclusion Criteria for Healthy Subjects:
- •Meet any of the exclusion criteria for diabetic or metabolic syndrome group Meet criteria for type 2 diabetes or metabolic syndrome
- •On medication for cholesterol or blood pressure.
- •History of allergy to local anesthetic injection like lidocaine.
研究组 & 干预措施
Hypoglycemia First
Individuals will undergo a hyperinsulinemic hypoglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit.
干预措施: Glycemic clamping (Other)
Euglycemia First
Individuals will undergo a hyperinsulinemic euglycemic clamp in their 1st study visit after passing screening, and a euglycemic clamp in their second visit.
干预措施: Glycemic clamping (Other)
结局指标
主要结局
Flow induced Dilation of the Brachial Artery (FMD%)
时间窗: 1 hour
次要结局
- Measurement of total and phosphorylated endothelium-derived NO synthase expression in radial artery endothelial cells.(1 hour)
- Measurement of mitochondrial membrane potential(1 hour)
- Mitochondrial superoxide production(1 hour)