This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Pramlintide acetate is a synthetic analog of the hormone amylin that occurs naturally in humans. In response to nutrient stimuli, amylin and insulin are secreted simultaneously by the pancreatic beta cells. The recnet discovery of amylin has enhanced our understanding of post-prandial glucose homeostatis. Patients with type 1 diabetes are deficient in both insulin and amylin. In the immediate post-prandial period, amylin is thought to suppress glucagon secretion that results in the suppression of glucose production by the liver, and the slowing down of gastric emptying. Pramlintide acetate has been reported to improve glycemic control in adults with type 1 or 2 diabetes. Specifically, psot-prandial glucose excursions are improved with adjunctive pramlintide use compared with insulin alone. Insulin action peaks during meals leading to post-prandial hypoglycemia.To avoid post-prandial hypoglycemia, we suggest administering pramlintide before meals, and insulin 15 minutes after ingesting a meal.Therefore, with this study we will compare glucose excursions when pre-meal pramlintide and post-meal insulin are administered with current standard therapy of insulin alone prior to meals.HYPOTHESISWe hypothesize that the administration of pramlintide, a synthetic analog of human hormone amylin, before meals, and insulin 15 mins after meals can improve or possibly avoid prandial hyperglycemia.
SPECIFIC AIMS The primary objective of this study is to examine the effect of pramlintide given pre-meal and insulin given just after meal ingestion on postprandial glucose excursions, and to compare these effects with those of standard therapy with pre-meal insulin.The secondary objective is to examine the effect of pramlintide and insulin on glucagon suppression in T1DM.Insulin replacement in the form of newer insulin analogs, and subcutaneous continuous insulin administration is imprefect giving rise to less than optimal blood glucose levels. Persistent poos gylcemic control leads to complications of major organ systems, leading to the detrioration of general well being and quality of life of the patient. This study will allow us to learn more about the previously and newly discovered hormones and synthetic analogs associated with glycemic control. With better understanding of the physiology of diabetes mellitus, we hope to achieve persistent optimal glycemic control that may delay or prevent complications.
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