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型糖尿病患者患热疾病的风险增加。在人体中，皮肤血管舒张剂对热应激的反应对于在热暴露或运动时保持体内温度所需的散热至关重要。2型糖尿病的皮肤血管并发症是公认的，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型糖尿病患者皮肤热调节血管舒张功能受损可能导致热疾病的风险增加；然而，没有关于2型糖尿病患者全身热应激期间皮肤血管扩张的信息。在本应用中，我们建议使用激光多普勒测量皮肤血流，通过静脉闭塞容积图测量前臂血流，以及局部药物阻断结合(a)直接（局部）加热皮肤，(b)全身加热2型糖尿病患者和年龄匹配的对照组，以解决以下具体目标：(1)测试是否当地皮肤血管舒张的热控制是减少2型DM。(2)量化贡献的感觉神经和一氧化氮的变化机制,当地气候变暖血管舒张2型DM。(3)来测试是否反射皮肤血管舒张反应全身热应力与2型DM减弱。(4)来测试是否改变反射在全身血管舒张热应力将降低交感神经活跃皮肤血管舒张,以及是否与一氧化氮的减少有关。我们对2型糖尿病患者皮肤血流调节的四种机制进行了评估，并与年龄和体型匹配的对照组进行了比较，这将为这些患者皮肤血流热调节控制的潜在危险障碍提供重要的见解。

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.