EVALUATION AND DIAGNOSIS OF DIABETIC ENTERIC NEUROPATHY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 1型糖尿病患者有腹胀、腹胀、腹胀和恶心的症状，通常被认为是自主神经病变。染色方法的局限性给这一诊断提供了病理上的确认，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中的无髓表皮神经进行染色。在糖尿病患者的胃和空肠上应用这些方法，我们发现肠粘膜神经变性，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。我们认为这是自主神经病变的第一个组织学证实。我们建议对I型胰腺移植患者的胃粘膜神经进行研究，以进一步表征我们的初步发现，制定诊断神经病变的特异性标准，并对肠细胞肥大进行量化。我们还将确定表皮神经是否可以替代肠神经病理诊断。除了诊断，这些结果还将提供有关正常胃和糖尿病胃的神经支配的新信息，有助于更好地了解调节异常、胃排空延迟和波动低血糖和高血糖的神经基础，并促进这一领域的研究。这项研究应该会让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促进预定胃排空的仪器的开发，作为预防低血糖的一种手段。它还可以为外科医生提供有关糖尿病手术后肠道运动潜力的知识，以便更合理地治疗术后肠道淤积。

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.