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

University of Virginia

Status: Completed

Conditions: Diabetes Mellitus, Type 1

Treatments: Other: CGM home test; Procedure: Metabolic Challenge Admission

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02663661

18568

DP3DK106907-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 73 patients

Sex: All

Ages: 12 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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73 participants in 3 patient groups

Autoantibody negative subjects

Other group

Description:

Subjects who are relatives of persons with T1DM and have tested negative for autoantibodies will have a Metabolic Challenge Admission followed by a CGM home test.

Treatment:

Other: CGM home test

Procedure: Metabolic Challenge Admission

One autoantibody subjects

Other group

Description:

Subjects who are relatives of persons with T1DM and have tested positive for one autoantibody will have a Metabolic Challenge Admission followed by a CGM home test..

Treatment:

Other: CGM home test

Procedure: Metabolic Challenge Admission

Two or more autoantibody subjects

Other group

Description:

Subjects who are relatives of persons with T1DM and have tested positive for two or more autoantibodies will have a Metabolic Challenge Admission followed by a CGM home test..

Treatment:

Other: CGM home test

Procedure: Metabolic Challenge Admission