Insulin-Glucose-Glucagon Network: Defining a Type 1 Diabetes Progression Index
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      The type 1 Diabetes (T1D) TrialNet Pathway To Prevention (PTP) Study assesses and recruits
      at-risk subjects into clinical trials aimed at preventing the development of full blown T1D.
      Thousands of first and second degree relatives of persons with T1D are screened for
      autoimmune abnormalities and positive subjects are followed with metabolic and autoantibody
      tests. The investigators' ancillary study us designed to test whether characterization of the
      insulin- glucose-glucagon (IGG) interactions in participants in the PTP study can provide new
      information about the early stages of the disease. When completed, this study will improve
      the understanding of the pathogenesis of the early stages of T1D and provide new quantitative
      tools for prediction and evaluation of insulin-glucagon-glucose interactions relevant to
      individuals at risk for developing T1D, thereby enabling future preventive intervention
      trials.
    

Detailed description: 
      The goal of the proposed ancillary studies is to establish whether characterization of the
      insulin-glucagon-glucose (IGG) interactions in first and second degree relatives of patients
      with type 1 diabetes (T1D) can provide new information about the pathogenesis, prediction,
      and progression of the early stages of the disease. The project will enroll individuals from
      the "Living Biobank" of the TrialNet Pathway to Prevention (PTP) study who are phenotyped
      with respect to a variety of risk factors, including immunological abnormalities. To the best
      of available knowledge, the IGG relationships in general and the glucagon phenotype in
      particular have not been studied in this population. It is known, however, that in T1D the
      release of glucagon is altered, which is manifested by abnormal postprandial suppression and
      defective response to hypoglycemia. Several reports indicate that glucagon becomes
      dysregulated prior to the development of T1D, but comprehensive studies aiming to understand
      in detail the insulin-glucagon co-dynamics in people at risk for T1D have never been
      performed.

      Thus, the goal now is to expand the investigators' existing methodology and transfer
      expertise in clinical testing and analysis of the IGG system to characterize the IGG
      interactions in individuals at risk for developing T1D.
    

Intervention name(s): Metabolic Challenge Admission; CGM home test
Intervention type(s): Procedure; Other
Intervention description(s): A ten hour clinical test involving drinking a liquid mixed meal followed four hours later by the induction of hypoglycemia with intravenous insulin administration.; A home study starting immediately after the clinical test during which participants will wear a continuous glucose monitor (CGM) for one week.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Diabetes Mellitus, Type 1 (T1DM); TrialNet; Pathway to Prevention (PTP); First and second degree relatives of persons with T1DM; Insulin-glucagon-glucose (IGG); Immunological risk to develop T1DM