New Therapeutic Targets in Pediatric Type 1 Diabetes

DESCRIPTION (provided by applicant): The Diabetes Control and Complications Trial (DCCT) demonstrated that most patients with type 1 diabetes (T1DM) should receive intensive treatment to lower the risks of complications. In children with diabetes, strict diabetes control is achieved at the expense of unacceptably high incidence of hypoglycemia. T1 DM is considered a bihormonal disease wherein there is insulin deficiency and glucagon dysregulation resulting in post-prandial hyperglycemia and pre-prandial hypoglycemia. In addition to glucagon we are now learning of other hormones that may contribute to the dyshormonogenesis of diabetes. One such hormone is amylin. Amylin is secreted by beta cells and is an exclusive glucagon suppressor. Amylin deficiency and glucagon dysregulation in T1 DM may result in abnormal glucose excursions often seen in T1 DM Current treatment of T1 DM employs the manipulation of insulin pharmacokinetics and diet to normalize glucose excursions with limited success despite the use of newer insulin analogs and insulin pumps. This proposal aims at using a novel two pronged approach using pramlintide, a synthetic form of amylin to combat post-prandial hyperglycemia and glucagon injection to prevent pre-prandial hypoglycemia. This study for the first time will investigate the pharmacotherapeutic role of amylin and glucagon in the prevention of hyper and hypoglycemia in T1 DM. The long-term goal is the understanding of pathophysiologic mechanisms in abnormal glucose homeostasis and facilitates the development of safe and new strategies to achieve glycemic control of T1 DM. The proposal describes a five-year training program for the development of an academic career in Pediatric Diabetology. The current proposal is an extension of previous work done by the principal investigator at Yale. This project utilizes new therapeutic modalities in prevention of hypo and hyperglycemia associated with the treatment of type 1 diabetes. The environment at Baylor will provide a combination of supervised research; scientific interchange, selected coursework and the candidate will obtain the training necessary to transition in to an independent investigator.