Insulin-Glucose-Glucagon Network: Defining a Type 1 Diabetes Progression Index

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.

Inclusion Criteria:

- Individuals 12 to 45 years old which have a brother, sister, child, or parent with
type 1 diabetes, or

- Individuals 12-20 years old who have have a cousin, aunt, uncle, niece, nephew,
half-brother, half-sister, or grandparent with type 1 diabetes.

Exclusion Criteria:

- Have diabetes already (type 1 or type 2)

- Have a medical condition or being been treated with medications that might interfere
with the study