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)，并出现恶心、腹胀和腹部不适。这项研究的主要目标是：1)确定T2 DM同胞中胃动力异常(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)研究急性激惹试验餐期间消化不良症状和胃动力障碍的机制；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)确定目前参加NIH赞助的一项研究的大规模、特征明确的社区T2 DM同胞人群中消化不良症状、GP和胃节律紊乱的患病率；2)将人口学、症状、实验室结果、胃动力测试数据和T2 DM伴和不伴GP的同胞对中的遗传成分联系起来；3)通过测量胃肌电活动和对挑衅性试验餐的反应选择的激素(例如Ghrelin、CCK和血管加压素)来研究GP和消化不良症状的机制；以及4)确定积极的血糖控制对消化不良症状和胃动力功能的影响。研究设计包括从1200名特征良好的T2 DM患者的数据库中招募200对兄弟姐妹。症状问卷、固相胃排空研究和具有刺激性试验餐的胃电记录将在5年内完成(长期研究)。这些研究的结果将在一项针对大量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。有无GP的T2 DM患者的一部分将在刺激性水负荷试验和卡路里膳食试验期间接受非侵入性生理测试和激素分析。这些研究的结果将为了解有无GP的T2 DM患者的餐后症状提供新的见解。在这项短期研究中，患有GP和HbA1c&Gt；8的患者将在6个月的时间内积极接受治疗，以获得正常的血糖水平和HbA1c水平，并与胃排空正常的T2 DM患者和HbA1C&lt；8的患者进行比较。治疗3个月和6个月后，将再次进行胃电测试，进行非卡路里和热餐测试，并在治疗6个月后进行固相胃排空测试。短期研究的结果将表明高血糖与T2 DM患者的症状、胃电节律紊乱和GP之间的相关性。在美国有一种T2 DM的流行，许多患者都有无法识别的胃动力障碍。这项拟议的研究将确定T2 DM患者中“糖尿病胃”的患病率，调查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