THE EFFECT OF PROLONGED PRAMLINTIDE INFUSION IN PEDIATRIC DIABETES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。普兰林肽是胰淀素的合成类似物。胰淀素是由胰腺细胞分泌的。在1型糖尿病（T1DM）中，胰岛素和胰淀素缺乏。胰岛素缺乏导致高血糖和代谢性酮症酸中毒。到目前为止，T1DM的治疗仅限于胰岛素替代。然而，胰淀素缺乏症的T1DM尚未得到治疗。我们刚刚了解到胰淀素在糖尿病中的作用。在研究中，普兰林肽有效地作为胰淀粉酶激动剂，可降低餐后高血糖。普兰林肽显著改善餐后高血糖的机制被认为是双重的。它能抑制混合膳食摄入后立即出现的餐后高胰高血糖素血症，也能延缓胃排空。我们正在进行的研究的初步数据表明，普兰林肽能很好地抑制餐后立即血糖升高，在某些情况下可能导致餐后立即低血糖。此外，餐后葡萄糖的正常上升也会消失。这可能是由于我们使用的普兰林肽剂量较高（45微克）和/或普兰林肽的递送方式所致。在这项研究中，我们希望验证这样一个假设，即如果普兰林肽以胰岛素：普兰林肽的比例递送，并在2小时内皮下输注，我们将看到葡萄糖漂移正常上升。我们进一步假设，与长期皮下输注相比，口服普兰林肽可显著抑制胃排空。

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. Pramlintide is a synthetic analog of amylin. Amylin is secreted by the beta cells of the pancreas. In Type 1 diabetes (T1DM), insulin and amylin are deficient. Insulin deficiency leads to hyperglycemia and metabolic ketoacidosis. The treatment of T1DM has so far been limited to insulin replacement. However, amylin deficiency in T1DM has not been treated. We are just learning of the role of amylin in diabetes. In studies, pramlintide effectively acts as an amylin agonist and results in lowering of post-prandial hyperglycemia. The mechanism by which pramlintide results in this marked improvement in post-prandial hyperglycemia is thought to be two-fold. It suppresses immediate post-prandial hyperglucagonemia that occurs with mixed meal intake and also delays gastric emptying. Our preliminary data from ongoing studies suggests that pramlintide suppressed immediate post-prandial glucose excursions so well that it may in some cases cause immediate post-prandial hypoglycemia. Also, there is a loss of normal rise in glucose excursions after a meal. This may have been due to the higher dose of pramlintide (45 mcg) that we used and/or due to the mode of delivery of pramlintide. In this study, we wish to test the hypothesis that if pramlintide is delivered as an insulin: pramlintide ratio and as a subcutaneous infusion over a 2 hour period, we will see a normal rise in glucose excursions. We further hypothesize that gastric emptying is acutely suppressed when pramlintide is given as a bolus as compared to a prolonged subcutaneous infusion.