CEREBRAL VASOREGULATION IN DIABETES

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是评估糖尿病自主神经病变伴直立性低血压OH对脑血管调节的影响，并确定糖尿病无症状性脑血管病的指标。OH是自主神经病变的最严重特征，并增加中风的风险。为了量化OH糖尿病自主神经病变对脑血管调节的影响，一项比较性实验研究将使用经颅多普勒TCD超声在非随机的OH糖尿病患者和40名非糖尿病对照组中评价脑动脉的血管反应性。脑血管调节将通过TCD在低碳酸血症和高碳酸血症、倾斜和快速血压变化期间测量的血流速度来测量。将确定有效血管调节的范围，以确定如果血管调节失败或血压下降至自动调节范围以下，在直立应激期间可能存在灌注不足风险的OH患者。将使用动脉自旋标记ASL以及3 T的T2加权FLAIR MRI，以确定和量化糖尿病自主神经病变中白色物质变化WMC的分布，OH指示无症状性低灌注。将开发模型，区分OH相关的WMC的MRI与非特异性年龄相关的变化，根据脑血管调节调整倾斜期间的血压下降和临床因素的指数。将按照方案分析从完成研究的受试者中获得的数据。这项研究可能有潜在的临床影响，它可能有助于确定老年糖尿病患者中风的风险。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this study is to assess the impact of diabetic autonomic neuropathy with orthostatic hypotension (OH) on cerebral vasoregulation and determine the factors indicative of silent cerebrovascular disease in diabetes. OH is the most severe feature of autonomic neuropathy and increases the risk for stroke. To quantify the effects of diabetic autonomic neuropathy with OH on cerebral vasoregulation, a comparative experimental study will evaluate vasomotor reactivity of cerebral arteries using transcranial Doppler (TCD) ultrasonography in non-randomized diabetic patients with and without OH and 40 non-diabetic controls. Cerebral vasoregulation will be measured from blood flow velocities measured by TCD during hypo- and hypercapnia, tilt-up and rapid blood pressure changes. The range of effective vasoregulation will be determined to identity the OH patients who might be at risk for hypoperfusion during orthostatic stress if vasoregulation fails or blood pressure declines below autoregulated range. An arterial spin labeling (ASL) will be used, as well as a T2 weighted (FLAIR) MRI at 3 Tesla to determine and quantify the distribution of white matter changes (WMC) in diabetic autonomic neuropathy with OH indicative of silent hypoperfusion. Models will be developed distinguishing OH-associated WMC on MRI from non-specific age-related changes, based on indices of cerebral vasoregulation adjusting for blood pressure decline during tilt and clinical factors. Data obtained from subjects who complete the study will be analyzed per protocol. This study may have potential clinical impact and it may help to identify the population of elderly diabetic patients at risk for stroke.