Gastroparesis, Gastric Dysrhythmias, and Dyspepsia Symptoms in Type 2 Diabetes

描述（由申请人提供）： 2型糖尿病（T2 DM）困扰着1400万患者;许多患者患有未确诊的胃轻瘫（GP），并患有恶心、腹胀和腹部不适。本研究的主要目的是：1）确定T2 DM同胞对中胃动力异常（例如GP、胃节律紊乱）和消化不良样症状的患病率和遗传成分; 2）研究急性激发性试验餐期间消化不良症状和胃动力功能障碍的机制; 3）确定高血糖治疗对消化不良症状和胃动力障碍的影响。具体目标是：1）确定目前在NIH赞助的研究中登记的具有T2 DM的兄弟姐妹对的大的、良好表征的、基于社区的群体中消化不良症状、GP和胃节律障碍的患病率; 2）关联具有和不具有GP的T2 DM的兄弟姐妹对的人口统计学、症状、实验室结果、胃动力测试数据和遗传成分; 3）通过测量胃肌电活动和选择的激素（例如，促生长素释放肽、胆囊收缩素和加压素）对刺激性试验餐的反应;和4）确定积极的葡萄糖控制对消化不良症状和胃运动功能的影响。研究设计包括从1200例特征良好的T2 DM患者的数据库中招募200对同胞。将在5年期间完成症状问卷调查、固相胃排空研究和刺激性试验餐的胃电图记录（长期研究）。这些研究的结果将在一项针对大型T2 DM人群的综合研究中确定胃病和消化不良症状的患病率。在激发性水负荷试验和热量餐试验期间，将对伴和不伴GP的T2 DM患者亚组进行无创生理学检查和激素测定。这些研究的结果将为T2 DM伴和不伴GP患者的餐后症状提供新的见解。在短期研究中，GP和HbA 1c>8的患者将接受积极治疗，以在6个月的时间段内获得正常的葡萄糖水平和HbA 1c水平，并与胃排空正常和HbA 1C <8的T2 DM患者进行比较。在治疗3个月和6个月后重复进行无热量和热量餐试验的胃电图试验，并在治疗6个月后进行固相胃排空试验。短期研究的结果将表明T2 DM患者中高血糖与症状、胃节律紊乱和GP的相关性。在美国，T2 DM流行，许多患者存在未被识别的胃动力障碍。本研究将确定2型糖尿病患者“糖尿病胃”的患病率，研究消化不良症状和胃神经肌肉功能障碍的机制，并评估高血糖在胃动力功能障碍中的作用

DESCRIPTION (provided by applicant): Type 2 diabetes mellitus (T2DM) afflicts 14 million patients; many patients have undiagnosed gastroparesis (GP) and suffer from nausea, bloating, and abdominal discomfort. Broad objectives of this study are to: 1) determine the prevalence and heritable components of gastric motility abnormalities (e.g. GP, gastric dysrhythmias) and dyspepsia-like symptoms in sibling pairs with T2DM; 2) investigate mechanisms of dyspepsia symptoms and gastric motility dysfunction during acute provocative test meals; and 3) determine the effect of treatment of hyperglycemia on dyspepsia symptoms and gastric motility disorders. Specific aims are: 1) to determine the prevalence of dyspepsia symptoms, GP, and gastric dysrhythmias in a large, well- characterized, community-based population of sibling pairs with T2DM currently enrolled in an NIH sponsored study; 2) to correlate demographics, symptoms, laboratory results, gastric motility test data, and hereditable components in sibling pairs with T2DM with and without GP; 3) to investigate mechanisms of GP and dyspepsia symptoms by measuring gastric myoelectrical activity and selected hormones (e.g., ghrelin, cholecystokinin, and vasopressin) in response to provocative test meals; and 4) to determine the effect of aggressive glucose control on dyspepsia symptoms and gastric motility function. Research design incorporates the recruitment of 200 sibling pairs from a data base of 1200 well-characterized T2DM patients. Symptom questionnaires, solid-phase gastric emptying studies and electrogastrogram recordings with provocative test meal will be completed over the 5 year period (Long-Term Study). Results from these studies will determine the prevalence of gastropathies and dyspepsia symptoms in a comprehensive study of a large population with T2DM. A subset of T2DM patients with and without GP will undergo non-invasive physiologic testing and hormone assays during a provocative water load test and a caloric meal test. Results of these studies will provide new insights into postprandial symptoms in patients with T2DM with and without GP. In the Short-Term Study, patients with GP and HbA1c >8 will be treated aggressively to obtain normal glucose levels and HbA1c levels during a 6 month time period and compared with T2DM patients with normal gastric emptying and HbA1C <8. Electrogastrogram testing with non-caloric and caloric meal tests will be repeated after 3 and 6 months and solid-phase gastric emptying tests after 6 months of therapy. Results from the Short-Term Study will indicate the relevance of hyperglycemia on symptoms, gastric dysrhythmias, and GP in patients with T2DM. There is an epidemic of T2DM in the United States and many patients have unrecognized stomach motility disorders. The proposed research will determine prevalence of the "diabetic stomach" in patients with T2DM, investigate mechanisms of dyspepsia symptoms and stomach neuromuscular dysfunction, and evaluate the role of hyperglycemia in stomach motility dysfunction