CLINICAL TRIAL: THE ROLE OF EXENATIDE IN TYPE I DIABETES MELLITUS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。T1 DM伴餐后高血糖与餐后高血糖相关。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安全有效的针对胰高血糖素的策略，并改善T1 DM的血糖控制。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。方案1的具体目的是建立与我们为普拉林肽建立的降糖剂量等同的T1 DM患者的埃塞那肽降糖剂量。为此，17名T1 DM患者将被随机分成4个不同剂量的普鲁米松研究。此外，还将评估胰高血糖素抑制和胃排空延迟。 与较低剂量相比，较高剂量的埃塞那肽对胃排空和胰升糖素抑制的影响更为显著。 具体目标 建立有效剂量的埃塞那肽，它将使餐后高血糖正常化，而不会引起低血糖。 目的：研究艾塞那肽对胃排空和胰高血糖素抑制的影响。 该方案的长期目标是开发一种安全的剂量，可用于新发的T1 DM患者。将测试艾塞那肽的抗凋亡特性，以确定在诊断早期使用艾塞那肽是否延长了β细胞的存活时间，从而延长了糖尿病的蜜月期。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 1 diabetes mellitus (T1DM) is currently managed using modulation of dietary carbohydrates and insulin. Parasoxical post-meal hyperglucagonemia is associated with psot-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 T1DM. The overall aim of this proposal is to develop safe and effective strategies targeting glucagon and improving glycemic control in pediatric T1DM. The specific aim of Protocol 1 is to establish a glucose-lowering dose of exenatide in T1DM equivalent to that which we have established for pramlintide. To this end 17 subjects with T1DM will be randomized to 4 studies with varying pramlintide doses. Glucagon suppression and delay in gastric emptying will also be assessed. Higher doses of exenatide will result in more pronounced effects on gastric emptying and glucagon suppression as compared to lower doses. SPECIFIC AIMS To establish an effective dose of exenatide, which will normalize post-prandial hyperglycemia without causing hypoglycemia. To determine the effects of exenatide on gastric emptying and glucagon suppression. The long-term objective of this protocol is to develop a safe exenatide dose that can be used in new onset patients with T1DM. The antiapoptic properties of exenatide will be tested to determine if using exenatide early in the diagnosis prolongs beta cell survival and hence prolonging of the honeymoon period of diabetes.