SCCOR in Hemostatic and Thrombotic Diseases Project 5 - Metabolic Causes of Thrombosis in Type 2 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Percent Changes in Endothelial Function as Measured by Flow Mediated Dilation by 2D Doppler Ultrasound on Day 2
研究概览
简要总结
Hypoglycemia (low blood glucose level) occurs frequently in intensively treated patients with diabetes. Although hypoglycemia was thought to occur almost exclusively in T1DM, with the advent of improved metabolic control in T2DM, the incidence of hypoglycemia is rising in these patients. Therefore in this application, we will test the novel hypothesis that prior hypoglycemia will result in (cardiovascular complications) during subsequent hypoglycemia.
详细描述
This study will test the hypothesis that 1) hypoglycemia causes a prothrombotic state and defective endothelial function and 2) episodes of repeated hypoglycemia will result in greater impairments of endothelial function and an increased prothrombotic tendency. Preliminary data in healthy men demonstrates that hypoglycemia can dramatically increase PAI-1 levels and the PAI-1 to tPA ratio, thereby creating a prothrombotic state. Whether this also occurs in type 2 DM patients is unknown. Furthermore, the effects of hypoglycemia on endothelial function in T2DM are also unknown.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •14 (7 female/ 7 male) Type 2 diabetic patients age 18-60 yrs
- •14 (7 female/ 7 male) Non-diabetic controls age and weight matched
- •Body mass index >20 kg/m2
- •Normal results of routine blood test to screen for hepatic, renal, and hematological abnormalities
- •Female volunteers of childbearing potential: negative HCG pregnancy test
- •Volunteers over 40 years old: normal baseline cardiac stress test
- •For those with type 2 diabetes: HBA1C >5.5%
- •For those with type 2 diabetes: diabetes < 20 years
- •For those with type 2 diabetes: C-peptide >0.2 nmol (1.1-4.4 ng/ml). If c-peptide is abnormal or there is a clinical suspicion of type 1 diabetes, MODY, or LADA, Anti-Islet cell (negative) and Glutamic Acid Decarboxylase (GAD) antibody negative (0.0-1.5 U/ml) will be performed
排除标准
- •Uncontrolled hypertension
- •History of cerebrovascular incidents
- •Pregnancy
- •Subjects unable to give voluntary informed consent
- •Subjects with a recent medical illness
- •Subjects on anticoagulant drugs, anemic, or with known bleeding diseases
- •Tobacco Use
- •Physical Exam Exclusion Criteria
- •Blood Pressure greater than 150/95
- •Clinically significant Cardiac Abnormalities (e.g. Heart Failure, Arrhythmias, ischemic tachycardia, S-T segment deviations, ect.) from history or from cardiac stress testing
- •Pneumonia
- •Hepatic Failure/Jaundice
- •Renal Failure
- •Acute Cerebrovascular/ Neurological deficit
- •Fever greater than 38.0 C
- •Screening blood tests exclusions according to protocol
研究组 & 干预措施
Control study then antecedent hypoglycemia study group
Day 1 euglycemia, day 2 hypoglycemia Hyperinsulinemic Hypoglycemic Clamp: hyperinsulinemic glucose clamp separated by 8 weeks then participants proceeded to antecedent hypoglycemia study Day 1 hypoglycemia, Day 2 hypoglycemia
干预措施: Hyperinsulinemic Hypoglycemic Clamp (Other)
Antecedent Hypoglycemic clamp study
Day 1 hypoglycemia, day 2 hypoglycemia Hyperinsulinemic Hypoglycemic Clamp: hyperinsulinemic glucose clamp separated by 8 weeks then participants proceeded to control study Day 1 euglycemia, Day 2 hypoglycemia
干预措施: Hyperinsulinemic Hypoglycemic Clamp (Other)
结局指标
主要结局
Percent Changes in Endothelial Function as Measured by Flow Mediated Dilation by 2D Doppler Ultrasound on Day 2
时间窗: baseline on day 2 and ~6 hours later at end of glucose clamp period
A measure of the baseline arterial dilation on day 2 is compared to the post intervention measure of dilation of the brachial artery on Day 2.
次要结局
未报告次要终点
研究者
Stephen N. Davis, MBBS
Professor
University of Maryland, Baltimore