Safety Study of Repeated Doses of Glucagon on Animal Starch in the Liver
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      The purpose of this study is to learn if giving multiple doses of a hormone called glucagon
      can cause a major decrease in liver glycogen (animal starch). Glucagon is currently approved
      by the Food and Drug Administration to be given as a large dose to treat severe low blood
      sugar. Our group is studying whether glucagon can be given in repeated small doses to prevent
      hypoglycemia.
    

Detailed description: 
      Hypoglycemia remains a barrier to optimal glucose control, which is necessary to prevent
      diabetes-related complications including eye, kidney, and nerve diseases. Despite treatment
      advances such as insulin pump therapy and continuous glucose monitoring, hypoglycemia remains
      a concern, even when insulin is given in a closed-loop system. A closed-loop system consists
      of a glucose-measuring device, from which data are collected and entered into an algorithm,
      which in turn controls insulin delivery. The difficulty of delivering regular or analog
      insulin in such a manner is related to its slow onset and prolonged effect when delivered
      subcutaneously. Until a more rapidly-acting insulin preparation is available, discontinuation
      of subcutaneous insulin during impending hypoglycemia, with any algorithm, may be
      insufficient to prevent hypoglycemia.

      Glucagon, a hormone secreted from the alpha cells of the normal endocrine pancreas, rapidly
      raises circulating glucose levels within minutes via glycogenolysis, even when given
      subcu-taneously. Glucagon is approved for use as a parenteral injection for treatment of
      severe hypoglycemia. Our group has successfully completed studies in humans using a
      closed-loop system that delivers insulin (in a nearly continuous fashion) to prevent and
      treat hyperglycemia as well as glucagon (intermittently) to prevent and treat hypoglycemia.

      However, it is unknown whether or not repeated doses lead to hepatic glycogen depletion,
      which would increase the risk of a severe hypoglycemic episode. 13C MRS (magnetic resonance
      spectroscopy) has been successfully used to quantify hepatic glycogen in a non-invasive
      fashion. We are proposing to use 13C MRS to compare glycogen stores in subjects with type 1
      diabetes after a period without glucagon vs after a period of repeated glucagon dosing. The
      comparisons will be made when glycogen stores should be replete (after a lunch meal) and when
      glycogen stores should be lower (after an overnight fast). If repeated doses of glucagon do
      cause glycogen depletion, then we would revise our dosing strategy in the closed-loop system
      and/or consider alternative methods for preventing hypoglycemia.
    

Intervention name(s): Glucagon
Intervention type(s): Drug
Intervention description(s): Subjects will receive 8 doses of glucagon, each dose will be 2.0 mcg per kg. Glucagon will be reconstituted immediately prior to administration and each dose will be administered subcutaneously via syringe/needle. The first glucagon dose is at hour 17, second at hour 22, third at hour 24, fourth at hour 27, fifth at hour 29, sixth at hour 31, seventh at hour 33, eighth at hour 35.
Other intervention name(s): GlucaGen
Intervention MeSH terms: Glucagon
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: diabetes; insulin; glucagon; glycogen; MRS