Visceral Afferent Dysfunction in Diabetic Gastropathy

糖尿病胃病的内脏传入功能障碍

• 批准号: 7615682
• 负责人: WILLIAM L HASLER
• 金额: $ 35.73万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7615682
• 关键词: Abdomen; Clinical; Clinical Research; Complications of Diabetes Mellitus; Defect; Development; Devices; Diabetes Mellitus; Diabetic Neuropathies; Disease; Double-Blind Method; Electric Stimulation; Electromyography; Enrollment; Erythromycin; Esthesia; Exhibits; Functional disorder; Future; Gastric Emptying; Gastric Pacemakers; Gastroparesis; Glycosylated hemoglobin A; Hyperalgesia; Hypersensitivity; Individual; Insulin; Intestines; Investigation; Longitudinal Studies; Measures; Motor; Natural History; Nausea; Nausea and Vomiting; Neural Conduction; Neuropathy; Pain; Pathogenesis; Patients; Perception; Peripheral; Pharmaceutical Preparations; Pharmacologic Substance; Placebo Control; Placebos; Prevalence; Protocols documentation; Psychometrics; Quality of life; Recording of previous events; Recruitment Activity; Relaxation; Research; Role; Satiation; Sensory; Severities; Stomach; Surveys; Symptoms; Testing; Visceral; Visceral Afferents; autonomic neuropathy; base; diabetic; functional improvement; implantation; improved; insight; psychologic; psychosocial; relating to nervous system; response; transmission process; treatment trial

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

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，并且治疗的改善与正常排空无关。因此，其他因素是糖尿病胃病症状的致病因素。据称，功能失调的内脏传入传输是功能性肠道疾病症状的基础。最近的研究表明，一些伴有恶心和腹胀的糖尿病患者存在痛觉过敏。我们假设：(1) 胃感觉改变在糖尿病性胃病中普遍存在，并且与症状相关；(2) 感觉异常与其他糖尿病神经病变相关；(3) 感觉改变与胃病的自然史相似；(4) 对治疗的反应与传入功能的改善有关。我们提议由胃轻瘫临床研究联盟实施 2 个多中心方案。患有超过 6 个月恶心、呕吐、腹胀、早饱或不适的糖尿病患者将被招募。第一个方案将通过饱腹感和恒压测试测量的胃感觉和调节缺陷与特定的胃病症状、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的测量联系起来。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。第二个方案将纵向追踪患有胃病的糖尿病患者。系列饱腹感、恒压器和胃排空测试将与周围和自主神经病变的临床参数和测量相关联，以比较糖尿病自然史中胃感觉与运动功能异常的发展。这项纵向研究中的部分患者将参加治疗试验。在使用纯促运动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、调节能力、知觉和排空情况。在单独的个体中，将在植入胃刺激器 (Enterra) 之前和之后 24 周进行胃测试，胃刺激器几乎没有促胃动力作用。双盲测试将以假刺激控制的方式进行，一半患者在测试前 4 周关闭设备。每种疗法的胃功能改善与症状减轻相关，以测试选择性针对运动功能障碍或增强内脏感觉的疗法是否能产生更大的益处。简单描述：恶心、呕吐和腹胀在长期糖尿病患者中很常见，严重影响生活质量。这些研究将深入了解糖尿病性胃病的症状发病机制，并将指导未来的研究，以纠正这种情况下的内脏感觉而非运动缺陷的疗法