Nitrate Supplementation and Exercise Tolerance in Patients With Type 2 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 2
- 主要终点
- Change in Skeletal Muscle Mitochondrial Function
研究概览
简要总结
The purpose of this study is to use a randomized, double-blind, placebo controlled study design to comprehensively investigate the impact of 8-weeks of dietary nitrate supplementation on skeletal muscle blood flow, mitochondrial function, and exercise capacity in patients with type 2 diabetes (T2D).
详细描述
Patients with type 2 diabetes (T2D) demonstrate a reduced exercise capacity, a powerful predictor of cardiovascular mortality, which may be due to reductions in skeletal muscle perfusion and mitochondrial dysfunction. Nitric oxide (NO) is a key molecule involved in in the regulation of blood flow to contracting muscles, as well as a critical mediator in mitochondrial respiration. However, there appears to be a decreased enzymatic synthesis of NO and an overall reduction of bioavailable NO in patients with T2D, which likely contributes to the reduced exercise capacity and tolerance. Accumulating evidence suggests that exogenous nitrate supplementation is an effective option for increasing NO bioavailability in vivo. The purpose of the proposal is to use a randomized, double-blind, placebo controlled study design to comprehensively investigate the impact of 8-weeks of dietary nitrate supplementation on skeletal muscle blood flow, mitochondrial function, and exercise capacity in patients with T2D. The central hypothesis is that increasing NO bioavailability via dietary nitrate supplementation in patients with T2D will lead to improved oxygen delivery and utilization during exercise. To address this hypothesis a highly mechanistic and translational experimental strategy will be used to explore whether increased NO bioavailability via dietary nitrate supplementation improves skeletal muscle perfusion during exercise (Aim 1), enhances mitochondrial biogenesis and function (Aim 2), and improves exercise capacity and efficiency (Aim 3). Collectively, these studies will provide important mechanistic insight into the therapeutic potential of dietary nitrate supplementation for improving skeletal muscle blood flow, mitochondrial function and exercise capacity in patients with T2D.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 77 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
- •Age is > or = 40 and < or = 77 years of age
- •Documented Type 2 diabetes
排除标准
- •diagnosis of type 2 diabetes < 3 years prior to enrollment
- •HbA1c <6.0% or >10.0%
- •body mass index > 42 kg/m2
- •incident cardiovascular events in the last year (heart attack, stroke)
- •symptomatic coronary artery disease and/or heart failure
- •uncontrolled hypertension
- •hypotension (resting systolic BP < 90 mmHg)
- •renal impairment with creatinine clearance (eGFR) of <50 ml/min
- •smoking or history of smoking within past one year
- •use of medication which contain nitrates
- •use of anti-coagulant drugs
- •use of anti-platelet drugs
- •participation in research studies in which medications or interventions are given which would potentially alter subject responses in the current study
- •For 15 age- and weight-matched nondiabetic control subjects
- •Inclusion Criteria:
- •Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
- •Age is > or = 40 and < or = 77 years of age
- •Exclusion Criteria:
- •Diagnosis of diabetes (Type 1 or Type 2)
- •body mass index > 42 kg/m2
- •incident cardiovascular events in the last year (heart attack, stroke)
- •symptomatic coronary artery disease and/or heart failure
- •uncontrolled hypertension
- •hypotension (resting systolic BP < 90 mmHg)
- •renal impairment with creatinine clearance (eGFR) of <50 ml/min
- •smoking or history of smoking within past one year
- •use of medication which contain nitrates
- •use of anti-coagulant drugs
- •use of anti-platelet drugs
- •participation in research studies in which medications or interventions are given which would potentially alter subject responses in the current study
结局指标
主要结局
Change in Skeletal Muscle Mitochondrial Function
时间窗: Pre and post 8 weeks of dietary nitrate supplementation
Muscle biopsies were obtained from the vastus lateralis using a Bergstrom needle with suction under local anesthesia, which will yield \~200-250mg of tissue. Mitochondrial function was assessed as follows: Fiber bundles were chemically permeabilized with saponin and mitochondrial respiration was analyzed by in situ high-resolution respirometry at 37°.
Maximal Exercise Capacity (VO2max)
时间窗: Pre and post 8 weeks of dietary nitrate supplementation
A 12-lead ECG, symptom limited cardiopulmonary exercise testing with gas exchange measurements will be performed on a cycle ergometer using a ramp protocol to determine maximal aerobic capacity (VO2max) and exercise efficiency.
Change in Skeletal Muscle Perfusion During Exercise
时间窗: Pre and post 8 weeks of dietary nitrate supplementation
Forearm blood flow will be determined using Doppler ultrasound during rhythmic forearm exercise.
次要结局
未报告次要终点
研究者
Darren P Casey
Assistant Professor
University of Iowa