Skin Blood Flow in Diabetes: Local and Reflex Control

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，患有2型糖尿病的个体似乎患热疾病的风险增加。 在人类中，皮肤血管舒张剂对热应激的反应对于在热暴露或运动期间维持内部体温所必需的散热是必不可少的。 2型糖尿病的皮肤血管并发症是公认的，局部血管舒张反应似乎在这种疾病中受损，尽管这些变化的机制尚不清楚。 2型糖尿病患者皮肤的温度调节血管舒张功能受损可能导致中暑风险增加;然而，没有关于2型糖尿病患者全身热应激期间皮肤血管舒张的信息。在本申请中，我们建议在2型糖尿病患者和年龄匹配的对照组中使用激光多普勒测量皮肤血流、通过静脉闭塞体积描记法测量前臂血流和局部药物阻断联合（a）皮肤直接（局部）加热和（B）全身加热，以解决以下特定目标：（1）测试2型糖尿病患者皮肤血管舒张的局部热控制是否减弱。 (2)量化感觉神经和一氧化氮机制对2型糖尿病局部血管舒张作用的影响。(3)检测2型糖尿病患者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减少，以及是否涉及一氧化氮贡献减少。 我们评估了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组相比，将为这些患者皮肤血流温度调节控制的潜在危险损害提供重要的见解。

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.