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，2型糖尿病患者患中暑的风险似乎增加。在人类中，皮肤血管扩张剂对热应激的反应性对于在热暴露或运动期间保持体内温度所需的热量散失是必不可少的。2型糖尿病的皮肤血管并发症是公认的，这种疾病的局部血管扩张剂反应性似乎受损，尽管这些变化的机制尚不清楚。2型糖尿病患者皮肤的热调节血管扩张受损可能导致中暑风险增加；然而，目前还没有关于2型糖尿病患者全身热应激期间皮肤血管扩张的信息。在这项应用中，我们建议使用激光多普勒测量皮肤血流量，通过静脉阻塞体积描记术测量前臂血流量，并结合局部药物阻断(A)直接(局部)加热皮肤，以及(B)在2型糖尿病患者和年龄匹配的对照组中进行全身加热，以解决以下特定目标：(1)测试2型糖尿病患者皮肤血管扩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在2型糖尿病局部增温血管扩张中的作用。(3)检测2型糖尿病患者对全身热应激的反射性皮肤血管扩张剂反应是否减弱。(4)检测全身热应激时反射性血管扩张的变化是否与皮肤交感神经活性血管扩张减少有关，以及是否与一氧化氮的贡献减少有关。我们对2型糖尿病患者与年龄和体型相匹配的对照组的皮肤血流调节的四种机制的评估，将为这些患者的皮肤血流温度调节控制的潜在危险损害提供重要的洞察。

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.