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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 1型糖尿病（T1 DM）目前通过调节饮食碳水化合物和胰岛素进行管理。 T1 DM患者餐后高胰高血糖素血症与餐后高血糖症相关。 胰高血糖素抑制剂，如胰淀素类似物普兰林肽和胰高血糖素样肽-1（GLP-1）类似物艾塞那肽，是批准用于成人糖尿病的新药物。 我们之前已经证明普兰林肽通过降低胰高血糖素和延迟T1 DM青少年的胃排空来降低餐后高血糖。 GLP-1在动物研究中已显示增加β细胞质量并减少细胞凋亡。 关于GLP-1在T1 DM中的使用，仅有有限的信息可用。 尚无研究报告确定普兰林肽和艾塞那肽是否对T1 DM患者的血糖控制具有相似作用。 本提案的总体目标是开发针对胰高血糖素和改善T1 DM血糖控制的安全有效策略。 本提案的总体目标是开发针对胰高血糖素和改善儿童T1 DM血糖控制的安全有效策略。 方案1的具体目的是确定艾塞那肽在T1 DM中的降糖剂量，该剂量与我们已确定的普兰林肽相当。 为此，将17例T1 DM受试者随机分配至4项不同普兰林肽剂量的研究。 还将评估胰高血糖素抑制和胃排空延迟。 与较低剂量相比，较高剂量的艾塞那肽将导致对胃排空和胰高血糖素抑制的更显著的作用。 具体目标 确定艾塞那肽的有效剂量，使餐后高血糖正常化而不引起低血糖。 确定艾塞那肽对胃排空和胰高血糖素抑制的影响。 本方案的长期目标是开发可用于新发T1 DM患者的安全艾塞那肽剂量。 将测试艾塞那肽的抗糖尿病特性，以确定在诊断早期使用艾塞那肽是否会降低β细胞存活，从而延长糖尿病的蜜月期。

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.