CONTINUOUS SUBCUTANEOUS INFUSION OF PRAMLINTIDE AND INSULIN: A RANDOMIZED DO

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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.