EXENATIDE (BYETTA) VS PRAMLINTIDE (SYMLIN)

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 摘要： 1型糖尿病(T1 DM)目前是通过调节饮食碳水化合物和胰岛素来管理的。矛盾的餐后高血糖与T1 DM的餐后高血糖相关。胰升糖素抑制药，如胰淀素类似物普拉林肽和胰升糖素样肽-1(GLP-1)类似物埃塞那肽，是被批准用于成人糖尿病的新药物。我们先前已经证明普拉林肽通过降低胰升糖素和延缓青少年T1 DM患者的胃排空来降低餐后高血糖。GLP-1在动物研究中已被证明可以增加β细胞质量，减少细胞凋亡。关于GLP-1在T1 DM中的使用，只有有限的信息可用。目前还没有研究确定普拉林肽和埃塞那肽对T1 DM患者的血糖控制是否有相似的效果。这项建议的总体目标是开发针对胰高血糖素的安全和有效的策略，并改善儿童T1 DM的血糖控制。在目前的方案中，我们假设埃塞那肽/普拉林肽在改善长期存在的T1 DM患者的血糖控制方面将比单独使用胰岛素更好。其次，对普拉林肽和埃塞那肽进行比较。埃塞那肽和/或普拉林肽的使用为我们提供了潜在的新工具来改善患有T1 DM的儿童和青少年的血糖控制，从而减少这种衰弱疾病的相关长期微血管并发症。 一、假设： 与单用胰岛素治疗相比，艾塞那肽或普拉林肽联合胰岛素辅助治疗可改善餐后血糖漂移。 二、具体目标： 1)观察在胰岛素基础上加用埃塞那肽和普鲁米诺对T1 DM患者血糖控制的影响，并与单纯胰岛素治疗进行比较。 2)比较普林肽与埃塞那肽联合应用胰岛素对T1 DM患者血糖控制的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT: Type 1 diabetes mellitus (T1DM) is currently managed using modulation of dietary carbohydrates and insulin. Paradoxical post-meal hyperglucagonemia is associated with post-prandial hyperglycemia in T1DM. Glucagon suppressors such as the amylin analog, pramlintide, and the glucagon like peptide-1 (GLP-1) analog, exenatide, are new agents approved for use in adults with diabetes. We have previously demonstrated pramlintide reduces post-prandial hyperglycemia by decreasing glucagon and delaying gastric emptying in adolescents with T1DM. GLP-1 in animal studies has been shown to increase beta cell mass and decrease apoptosis. Only limited information is available on the use of GLP-1 in T1DM. No studies have been reported to determine if pramlintide and exenatide have similar effects on glycemic control in T1DM. The overall aim of this proposal is to develop safe and effective strategies targeting glucagon and improving glycemic control in pediatric T1DM. In current protocol, we hypothesize that exenatide/pramlintide will be better than insulin alone in improving glycemic control in longstanding T1DM. Secondarily comparisons between pramlintide and exenatide will be undertaken. Uses of exenatide and/or pramlintide provide us with potentially new tools to improve glycemic control in children and adolescents with T1 DM and thus reduce associated long-term microvascular complications of this debilitating disease. I. HYPOTHESIS: Postprandial glucose excursions improve with adjunctive therapy of exenatide or pramlintide with insulin as compared to mono-therapy of insulin. II. SPECIFIC AIMS: 1) To examine the effect of exenatide vs pramlintide adjunctive therapy in addition to insulin on glycemic control in T1DM as compared to mono-therapy of insulin. 2) To compare the efficacy of pramlintide vs exenatide when combined with insulin on glycemic control in T1DM.