THE EFFECT OF PROLONGED PRAMLINTIDE INFUSION IN PEDIATRIC DIABETES

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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. 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.