Visceral Afferent Dysfunction in Diabetic Gastropathy

描述（由申请人提供）： 糖尿病性胃病，表现为恶心、呕吐、腹胀和疼痛，被认为是胃轻瘫的同义词，因为许多患者表现出胃排空延迟。然而，排空率与症状相关性较差，治疗改善与排空正常化无关。因此，其他因素是糖尿病胃病症状的致病因素。内脏传入传递功能障碍据称是功能性肠病症状的基础。最近的研究表明，痛觉过敏存在于一些糖尿病患者的恶心和腹胀。我们假设：（1）胃感觉改变在糖尿病性胃病中普遍存在，并与症状相关，（2）感觉异常与其他糖尿病性神经病相关，（3）感觉改变与胃病的自然病程平行，（4）对治疗的反应与传入功能改善相关。我们建议由胃轻瘫临床研究联盟进行2个多中心方案。将招募具有>6个月恶心、呕吐、腹胀、早饱或不适的糖尿病患者。第一个方案将通过饱腹感和恒压器试验测量的胃感觉和调节缺陷与特定胃病症状、糖尿病并发症、心理社会参数、生活质量测量、胃排空以及周围和自主神经病变测量相关。这些研究将量化糖尿病胃病传入功能障碍的患病率，并评估其在这种情况下症状发展中的潜在致病作用。第二个方案将纵向跟踪糖尿病胃病患者。系列饱腹感、恒压器和胃排空试验将与周围神经和自主神经病变的临床参数和测量值相关，以比较在糖尿病自然史中何时出现异常胃感觉与运动功能。本纵向研究中的患者亚组将入组治疗试验。在使用纯促动力药物红霉素与安慰剂进行双盲治疗之前和12周时，将量化饱腹感、调节、感知和排空。在单独的个体中，将在胃刺激器（Enterra）植入前和植入后24周进行胃测试-胃刺激器几乎没有促动力作用。双盲测试将以假刺激对照方式进行，其中一半患者在测试前4周关闭器械。每种治疗的胃功能改善将与症状减轻相关，以测试选择性靶向运动功能障碍或内脏感觉增强的治疗是否产生更大的益处。简单描述：恶心、呕吐和腹胀在长期糖尿病患者中很常见，并明显损害生活质量。这些研究将为糖尿病胃病的症状发病机制提供深入的了解，并将指导未来的治疗研究，纠正内脏感觉而不是运动缺陷，在这种情况下，

DESCRIPTION (provided by applicant): Diabetic gastropathy, presenting as nausea, vomiting, bloating, and pain, has been considered synonymous with gastroparesis as many patients exhibit delayed gastric emptying. Yet, emptying rates correlate poorly with symptoms and improvements on therapy do not associate with normalized emptying. Thus, other factors are pathogenic of gastropathic symptoms in diabetes. Dysfunctional visceral afferent transmission purportedly underlies symptoms in functional bowel disorders. Recent studies have shown that hyperalgesia is present in some diabetics with nausea and bloating. We hypothesize: (1) altered gastric sensation is prevalent in diabetic gastropathy and correlates with symptoms, (2) sensory abnormalities relate to other diabetic neuropathies, (3) altered sensation parallels the natural history of gastropathy, and (4) responses to therapy relate to improved afferent function. We propose 2 multicenter protocols to be conducted by the Gastroparesis Clinical Research Consortium. Diabetics with >6 months of nausea, vomiting, bloating, early satiety, or discomfort will be recruited. The first protocol will relate gastric sensory and accommodation defects, measured by satiety and barostat tests, to specific gastropathy symptoms, diabetic complications, psychosocial parameters, quality of life measures, gastric emptying, and measures of peripheral and autonomic neuropathy. These studies will quantify the prevalence of afferent dysfunction in diabetic gastropathy and assess its potential pathogenic role in symptom development in this condition. The second protocol will follow diabetics with gastropathy longitudinally. Serial satiety, barostat, and gastric, emptying tests will be correlated with clinical parameters and measures of peripheral and autonomic neuropathy to compare when abnormal gastric sensory vs. motor function develop in the natural history of diabetes. Subsets of patients in this longitudinal study will enroll in treatment trials. Satiety, accommodation, perception, and emptying will be quantified before and at 12 weeks of double-blind therapy with the pure prokinetic drug erythromycin vs. placebo. In separate individuals, gastric testing will be performed before and 24 weeks after implantation of the gastric stimulator (Enterra)-which has little prokinetic action. Double-blind testing will occur in sham-stimulation controlled fashion with the device turned OFF in half of patients 4 weeks before testing. Gastric function improvements with each therapy will be correlated with symptom reductions to test if therapies that selectively target motor dysfunction or heightened visceral sensation produce greater benefits. Lay description: Nausea, vomiting and bloating are prevalent in patients with long-standing diabetes and markedly impair quality of life. These studies will provide insight into symptom pathogenesis in diabetic gastropathy and will direct future research into therapies that correct visceral sensory rather than motor defects in this condition