EVALUATION AND DIAGNOSIS OF DIABETIC ENTERIC NEUROPATHY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。1型糖尿病患者伴有腹饱、腹胀、腹胀和恶心等症状，通常被认为患有自主神经病变。染色方法的局限性为该诊断提供了病理证实，并限制了研究。多年来，我们一直使用免疫组织化学方法对皮肤无髓鞘表皮神经进行染色。用这些方法对糖尿病患者的胃和空肠进行观察，发现肠黏膜神经变性、血管扩张、肠细胞肥大。受影响的神经主要是向大脑和脊髓提供有关管腔内容物的感觉输入，以调节蠕动和分泌反射的传入神经。我们认为这是自主神经病变的第一个组织学证实。我们建议研究I型胰腺移植候选者的胃粘膜神经，以进一步确定我们的初步发现，制定神经病变诊断的具体标准，并量化肠细胞肥大。我们还将确定表皮神经是否可以作为肠神经病理诊断的替代品。除诊断外，该结果还将提供关于正常胃和糖尿病胃神经支配的新信息，从而更好地理解异常调节、胃排空延迟和波动性低血糖和高血糖的神经基础，并刺激该领域的研究。这项研究将使患者更好地了解使血糖控制复杂化的因素，从而改善管理。我们希望这项研究将促进仪器的发展，以促进胃排空作为预防低血糖的一种手段。它也可以为外科医生提供手术后糖尿病肠道运动电位的知识，以便更合理地治疗术后肠瘀。

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. Patients with type 1 diabetes and symptoms of abdominal fullness, bloating, distention and nausea are usually considered to have autonomic neuropathy. Limitations of staining methods have presented pathological confirmation of this diagnosis and restricted research. We have used immunohistochemical methods to stain unmyelinated epidermal nerves in skin for many years. Using these methods on stomach and jejunum of diabetic patients we discovered degeneration of enteric mucosal nerves, dilated blood vessels, and hypertrophic enterocytes. The affected nerves are mainly afferents that provide the sensory input about lumen contents to the brain and spinal cord for modulation of peristaltic and secretory reflexes. We believe that this is the first histological confirmation of autonomic neuropathy. We propose to study mucosal nerves of the stomach in type I candidates for pancreas transplantation to further charcterize our initial findings, to develop specific criteria for diagnosis of neuropathy, and to quantify entercyte hypertrophy. We will also determine whether epidermal nerves can act as surrogates for diagnosis of enteric nerve pathology. In addition to diagnosis, the results will provide new information about the innervation of the normal and diabetic stomach, lead to better understanding of the neural basis of abnormal accomodation, delayed gastic emptying and fluctuating hypo- and hyperglycemia, and stimulate research in this field. This research should lead to better patient understanding of the factors that complicate blood glucose control thereby leading to improved management. We hope the research will stimulate development of instruments to promote scheduled gastric emptying as a means to prevent hypoglycemia. It can also provide surgeons with knowledge of the motility potential of operated diabetic intestine for more rational therapy of postoperative intestinal stasis.