Skin Blood Flow in Diabetes: Local and Reflex Control

糖尿病中的皮肤血流：局部和反射控制

• 批准号: 7008863
• 负责人: NISHA CHARKOUDIAN
• 金额: $ 28.81万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-10 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7008863
• 关键词: afferent nerve; angiotensin II; arm; body composition; body temperature regulation; clinical research; electrocardiography; exercise; glucose tolerance test; human subject; hyperthermia; microdialysis; nitric oxide; noninsulin dependent diabetes mellitus; nontherapeutic iontophoresis; plethysmography; skin circulation; ultrasound blood flow measurement; vasodilation

The incidence of type 2 diabetes mellitus (DM) continues to rise rapidly in the United States. During heat stress, individuals with type 2 DM appear to be at increased risk for development of heat illness. In humans, cutaneous vasodilator responsiveness to thermal stress is essential for the heat dissipation necessary to maintain internal body temperature during heat exposure or exercise. Cutaneous vascular complications of type 2 DM are well-recognized, and local vasodilator responsiveness appears to be impaired in this disease, although the mechanisms for these changes are not clear. Impaired thermoregulatory vasodilation in the skin of patients with type 2 DM could contribute to the increased risk of heat illness; however, no information exists regarding cutaneous vasodilation during whole body heat stress in patients with type 2 DM. In this application, we propose to use laser-Doppler measurements of skin blood flow, measurements of forearm blood flow by venous occlusion plethysmography, and local pharmacological blockade in combination with (a) direct (local) heating of the skin, and (b) whole-body heating in patients with type 2 DM and age-matched controls to address the following specific aims: (1) To test whether local thermal control of cutaneous vasodilation is diminished with type 2 DM. (2) To quantify changes in contributions of sensory nerve and nitric oxide mechanisms to local warming vasodilation in type 2 DM. (3) To test whether the reflex cutaneous vasodilator response to whole body heat stress is diminished with type 2 DM. (4) To test whether any changes in reflex vasodilation during whole body heat stress are due to decreased sympathetic active vasodilation in the skin, and whether a decreased contribution of nitric oxide is involved. Our assessment of four mechanisms of skin blood flow regulation in patients with type 2 DM compared to control subjects matched for age and body size will provide important insight into potentially dangerous impairments of thermoregulatory control of skin blood flow in these patients.

在美国，2 型糖尿病 (DM) 的发病率持续快速上升。 在热应激期间，2 型糖尿病患者出现热病的风险似乎更高。 在人类中，皮肤血管舒张剂对热应激的反应对于热暴露或运动期间维持体内体温所必需的散热至关重要。 2 型糖尿病的皮肤血管并发症已得到充分认识，并且局部血管扩张剂反应性似乎在这种疾病中受损，尽管这些变化的机制尚不清楚。 2 型糖尿病患者皮肤温度调节血管舒张受损可能导致热病风险增加；然而，尚无关于 2 型糖尿病患者全身热应激期间皮肤血管舒张的信息。在此应用中，我们建议使用激光多普勒测量皮肤血​​流量、通过静脉闭塞体积描记法测量前臂血流量以及局部药理学阻断，结合（a）直接（局部）加热皮肤，和（b）2型糖尿病患者和年龄匹配对照的全身加热，以实现以下具体目标：（1）测试皮肤的局部热控制是否有效。 2 型糖尿病的血管舒张作用减弱。 (2) 量化感觉神经和一氧化氮机制对 2 型糖尿病局部变暖血管舒张的贡献变化。 (3) 测试2型糖尿病对全身热应激的反射性皮肤血管舒张反应是否减弱。 (4) 测试全身热应激期间反射性血管舒张的任何变化是否是由于皮肤中交感神经活性血管舒张的减少以及是否涉及一氧化氮贡献的减少。 我们对 2 型糖尿病患者皮肤血流调节的四种机制与年龄和体型匹配的对照受试者进行比较的评估，将为了解这些患者皮肤血流温度调节控制的潜在危险损伤提供重要的见解。