Visceral Afferent Dysfunction in Diabetic Gastropathy

糖尿病胃病的内脏传入功能障碍

• 批准号: 7497372
• 负责人: WILLIAM L HASLER
• 金额: $ 0.98万
• 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/7497372
• 关键词: Abdomen; Clinical; Clinical Research; Complications of Diabetes Mellitus; Condition; 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; Rate; Recording of previous events; Recruitment Activity; Relaxation; Research; Role; Satiation; Score; Sensory; Severities; Stomach; Surveys; Symptoms; Testing; Visceral; Visceral Afferents; Week; autonomic neuropathy; base; diabetic; functional improvement; implantation; improved; insight; psychologic; psychosocial; relating to nervous system; response; transmission process; treatment trial

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 wiirbe correlated with clinical parameters and measures of peripheral and autonomic neuropathy to compare when abnormal gastric sensoryvs. 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.

糖尿病胃病，表现为恶心、呕吐、腹胀和疼痛。 胃瘫的代名词，因为许多患者表现出胃排空延迟。然而，空置率 与症状的相关性很差，治疗的改善与正常化的排空无关。 因此，其他因素也是糖尿病胃病症状的致病因素。内脏传入功能障碍 据称，传播是功能性肠病症状的基础。最近的研究表明， 有些糖尿病患者会出现痛觉过敏，伴有恶心和腹胀。我们假设：(1)胃改变 感觉在糖尿病胃病中普遍存在，并与症状相关，(2)感觉异常与 对于其他糖尿病神经病变，(3)感觉改变与胃病的自然病史相似，以及(4) 对治疗的反应与改善传入功能有关。我们建议两个多中心协议为 由胃瘫临床研究联盟进行。有6个月恶心症状的糖尿病患者， 会出现呕吐、腹胀、早饱或不适。第一个方案将与胃感觉有关 通过饱腹感和恒压测试测量的调节缺陷，到特定的胃病症状， 糖尿病并发症，心理社会参数，生活质量测量，胃排空，和测量 周围神经和自主神经病变。这些研究将量化传入功能障碍的患病率 糖尿病胃病，并评估其在这种情况下症状发展的潜在致病作用。这个 第二个方案将纵向跟踪患有胃病的糖尿病患者。一连串的饱腹感，恒压计，还有胃部， 排空试验与外周和自主神经的临床参数和测量相关 比较神经病变时胃感觉异常与VS。运动功能在人类自然历史中的发展 糖尿病。这项纵向研究中的部分患者将参加治疗试验。饱腹感，食宿， 知觉和排空将在纯药物双盲治疗前和12周时进行量化。 促动力药物红霉素与安慰剂。对于不同的个体，胃测试将在之前和 无促动力作用的胃电刺激器(Enterra)植入24周后。双倍- 在一半的患者关闭该设备的情况下，将以假刺激控制的方式进行盲测 在测试前几周。每种疗法对胃功能的改善将与症状相关 减少以测试选择性针对运动功能障碍或增强内脏感觉的治疗 产生更大的效益。患者描述：恶心、呕吐和腹胀在慢性胃炎患者中普遍存在。 患有糖尿病，并明显损害生活质量。这些研究将提供对症状的洞察 糖尿病胃病的发病机制，并将指导未来的研究，以纠正脏腑的疗法 在这种情况下是感觉缺陷而不是运动缺陷。