CONTINUOUS SUBCUTANEOUS INFUSION OF PRAMLINTIDE AND INSULIN: A RANDOMIZED DO

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， 因此可以在其他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的研究机构。 摘要 1型糖尿病（T1 DM）是由于胰腺β细胞的自身免疫性破坏而发生的。 胰腺的β细胞共同分泌两种激素胰岛素和胰淀素。 胰岛素缺乏可恢复血糖波动，但不能使血糖水平正常化，尤其是餐后血糖浓度升高。 胰淀素的合成类似物普兰林肽替代激素可降低餐后高血糖。 然而，普兰林肽递送的平台，即在餐前给予注射，导致餐后立即降低葡萄糖的不期望的效果。 如果普兰林肽在较长时间内给药，我们发现其模拟胰淀素的更生理性递送。 在基础条件下，存在胰岛素和胰淀素分泌，并且与此一致，我们假设患有T1 DM的患者需要两种激素被替换以使葡萄糖波动正常化。 假设 我们假设，与安慰剂相比，持续同时皮下注射胰岛素和连续注射普兰林肽将降低吸收后和餐后状态下的血糖波动。 具体目标 1.测定皮下输注普兰林肽后24小时内血浆普兰林肽和胰岛素浓度的药效学和药代动力学特征。 2. 确定普兰林肽连续输注和降低胰岛素剂量与安慰剂（普兰林肽）和胰岛素相比对血糖波动、胃排空和胰高血糖素浓度的影响。

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. ABSTRACT Type 1 diabetes (T1DM) occurs due to the autoimmune destruction of beta cells of the pancreas. Beta cells of the pancreas co-secrete two hormones insulin and amylin. Insulin deficiency restores glucose excursions but does not normalize glycemic levels especially psot-prandial blood glucose concentrations are elevated. Hormone replacement with pramlintide a synthetic analog of amylin decreases post-prandial hyperglycemia. However, the platform of pramlintide delivery i.e. given a an injection prior to the meal results in an undersirable effect of immediate post-prandial glucose lowering. If pramlintide is given over a prolonged period of time we have found that to mimic a more physiologic delivery of amylin. In the basal conditions there is insulin and amylin secretion and in keeping with that we hypothesize that patients wih T1DM require both hormones to be replaced to normalize glucose excursions. HYPOTHESIS We hypothesize that continuous simultaneous subcutaneous insulin and adjunctive pramlintide will decrease glucose excursion in the post-absorptive as well as the post-prandial state as compared to placebo. SPECIFIC AIM 1, To determine the pharmacodynamic and pharmacokinetic profile of plasma pramlintide and insulin concentrations after subcutaneous infusion administration of pramlintide during a twenty four hour period. 2. To determine the effect of giving pramlintide as a continuous infusion and drecreased insuling dosage vs. placebo (pramlintide) and insulin on glucose excursions, gastric emptying and glucagon concentration.