The Role of Amylin and Glucagon in T1DM
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to see if giving pramlintide and insulin before a meal would
      lower high blood sugar and if a glucagon (a naturally made hormone in the body but reduced in
      diabetes and its role is in prevention of low blood sugar) shot given in the late "after
      meal" time would prevent low blood sugar. The studies outlined in this proposal might help in
      developing new treatment options to target "after meal" high blood sugar and before meal low
      blood sugar in children. This would possibly help improve overall blood sugar control and
      prevent the long-term complications of diabetes.
    

Detailed description: 
      Objective: To develop a new treatment approach in the prevention of hypo and hyperglycemia in
      children with type 1diabetes.

      Background/Rationale: The diabetes control and complications trial (DCCT) showed that
      improving blood sugar control for individuals with type 1 diabetes (T1DM) stopped or delayed
      the onset of long-term complications. As a result of the study, intensive management to
      control blood sugar and glycosylated hemoglobin as near to normal as safely as possible is
      advocated. However, hypoglycemia was increased 3 fold in the DCCT study and is the major
      limiting factor in gaining "tight" control of blood sugar in T1DM.

      Description of Project: In health individuals, "after meal" blood sugar level is very
      carefully controlled. Insulin (the hormone that lowers blood sugar) and glucagon (the hormone
      that raises blood sugar) play a key role in maintaining this careful balance. Recently we
      understand that a hormone called amylin also contributes to this careful after meal blood
      glucose balance. Amylin in the immediate after meal period works by reducing glucagon, which
      in turn reduces the liver releasing stored sugar into the blood stream.

      In T1DM, there is the lack of insulin and failure of glucagon suppression leading to
      hyperglycemia immediately following when food is eaten. Also, glucagon is not regulated
      correctly after a meal. The glucagon normally produced by the body does not increase in
      response to hypoglycemia thus interfering with the delicate balance between glucose
      production and glucose used. Therefore, it is difficult to get normal blood sugar when
      someone has type1 diabetes.

      Currently, the treatment for mild to moderate hypoglycemia causing a sudden feeling of racing
      heart, feeling sweaty, weak or hungry is to eat or drink carbohydrate in the awake person.
      Severe hypoglycemia (unconsciousness due to low blood sugar) is treated with a glucagon shot.
      Unfortunately, there are no treatments to prevent mild or severe hypoglycemia.

      The purpose of this study is to see if giving pramlintide (manmade amylin) and insulin before
      a meal would lower hyperglycemia and if a glucagon shot given in the late "after meal" time
      would prevent hypoglycemia and allow the blood sugar levels to improve in people with T1DM.
      The studies outlined in this proposal might help in developing new treatment options to
      target "after meal" hyperglycemia high blood glucose and before meal hypoglycemia in
      children. This study for the first time will investigate the role of glucagon in the
      causation of hyperglycemia and its role in the prevention of hypoglycemia.

      Relevance to Type 1 diabetes: Using naturally occurring hormones that are dysregulated or
      deficient in T1DM we wish to restore normal glucose concentration in T1DM. Such treatment if
      successful would be a major breakthrough in the prevention of hyper and hypoglycemia and in
      decreasing both short and long-term complications associated with T1DM.
    

Intervention name(s): Pramlintide and glucagon
Intervention type(s): Drug
Intervention MeSH terms: Pramlintide; Glucagon
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: type 1 diabetes; hypoglycemia; hyperglycemia