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

NCT02663661 | Completed DMC

• 2 other identifiers: 18568DP3DK106907-01
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 1

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

Outcome Measures

Primary Outcomes (1)

• Test the hypothesis that immunological abnormalities are associated with abnormally high glucagon responses to a meal and reduced glucagon responses to insulin induced hypoglycemia.

  To address this aim, subjects in all three groups which are at different level of immunological risk to develop T1D will undergo a single 10-hour clinical test consisting of a mixed meal drink followed by insulin-induced hypoglycemia (Metabolic Challenge) to estimate their postprandial and counterregulatory glucagon responses.

  Approximately 10 hours

Secondary Outcomes (1)

• Correlate metrics derived from a minimally-invasive Continuous Glucose Monitor (CGM) home test with glucagon responses to a meal and hypoglycemia measured in the hospital.

  Seven days

Study Arms (3)

Autoantibody negative subjects

OTHER

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.

Procedure: Metabolic Challenge Admission; Other: CGM home test

One autoantibody subjects

OTHER

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..

Procedure: Metabolic Challenge Admission; Other: CGM home test

Two or more autoantibody subjects

OTHER

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..

Procedure: Metabolic Challenge Admission; Other: CGM home test

Interventions

Metabolic Challenge Admission PROCEDURE

A ten hour clinical test involving drinking a liquid mixed meal followed four hours later by the induction of hypoglycemia with intravenous insulin administration.

Autoantibody negative subjects; One autoantibody subjects; Two or more autoantibody subjects

CGM home test OTHER

A home study starting immediately after the clinical test during which participants will wear a continuous glucose monitor (CGM) for one week.

Autoantibody negative subjects; One autoantibody subjects; Two or more autoantibody subjects

Eligibility Criteria

• Age: 12 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Have diabetes already (type 1 or type 2)
• Have a medical condition or being been treated with medications that might interfere with the study

Sponsors & Collaborators

• University of Virginia: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Virginia, Center for Diabetes Technology

Charlottesville, Virginia, 22903, United States

Location

Related Publications (1)

• Montaser E, Breton MD, Brown SA, DeBoer MD, Kovatchev B, Farhy LS. Predicting Immunological Risk for Stage 1 and Stage 2 Diabetes Using a 1-Week CGM Home Test, Nocturnal Glucose Increments, and Standardized Liquid Mixed Meal Breakfasts, with Classification Enhanced by Machine Learning. Diabetes Technol Ther. 2023 Sep;25(9):631-642. doi: 10.1089/dia.2023.0064. Epub 2023 Jun 15.

  PMID: 37184602 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Leon Farhy, PhD

  UVA Center for Diabetes Technology

  PRINCIPAL INVESTIGATOR

• Sue A Brown, MD

  UVA Center for Diabetes Technology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: January 26, 2016
• Study Start: March 16, 2016
• Primary Completion: June 30, 2019
• Study Completion: June 30, 2019
• Last Updated: July 23, 2019

Record last verified: 2019-07

Locations

US (1)