Identification of β Cell Dysfunction in Relatives of Individuals With Type 1 Diabetes Mellitus

NCT ID: NCT04362917

Last Updated: 2023-03-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 70 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-11-14
• Study Completion Date: 2021-08-27

Brief Summary

Despite the valuable information derived from older studies evaluating type 1 diabetes, the diabetes research community has, in large part, overlooked potential contributions of baseline abnormalities in β cell function to T1D development. Newer studies focusing on higher risk individuals often exclude family members without evidence of positive islet autoantibodies. New technologies to assay alternative biomarkers of β cell stress and death remain incompletely explored in both Ab negative and Ab positive family members of T1D patients. Specifically, modern biomarkers of β cell dysfunction have not been rigorously tested in combination with metabolic testing to fully understand their association with insulin secretion.

The investigator's working hypothesis is that individuals at genetic risk for T1D exhibit baseline β cell dysfunction, even before development of detectable islet autoimmunity (seropositivity for islet Abs).

Conditions

Type 1 Diabetes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

FDR-

Adults with a first degree relative with T1D, who have tested negative for islet autoantibodies.

There is no intervention. Each group will get a MMTT and a clamp to evaluate beta cell function, identify elevations in circulating biomarkers of β cell stress or death, as well as their associations with measures of β cell function, and compare advantages of hyperglycemic clamps in identifying β cell dysfunction in this setting, relative to the mixed meal tolerance test (MMTT). They will repeat both the MMTT and the clamp once, to assess inter-test variability.

There is no intervention

Intervention Type: OTHER

There is no intervention

FDR+

Adolescents and adults with a first or second degree relative with T1D, who has tested positive for at least one islet autoantibody.

There is no intervention. Each group will get a MMTT and a clamp to evaluate beta cell function, identify elevations in circulating biomarkers of β cell stress or death, as well as their associations with measures of β cell function, and compare advantages of hyperglycemic clamps in identifying β cell dysfunction in this setting, relative to the mixed meal tolerance test (MMTT). They will repeat both the MMTT and the clamp once, to assess inter-test variability.

There is no intervention

Intervention Type: OTHER

There is no intervention

Control

Adults with no family history of Type 1 Diabetes, who have tested negative for islet autoantibodies

There is no intervention. Each group will get a MMTT and a clamp to evaluate beta cell function, identify elevations in circulating biomarkers of β cell stress or death, as well as their associations with measures of β cell function, and compare advantages of hyperglycemic clamps in identifying β cell dysfunction in this setting, relative to the mixed meal tolerance test (MMTT). They will repeat both the MMTT and the clamp once, to assess inter-test variability.

There is no intervention

Intervention Type: OTHER

There is no intervention

Interventions

There is no intervention

There is no intervention

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Nonrelative controls: Male and female adults 18-55 years old with no family history of Type 1 Diabetes, who have tested negative for glutamic acid decarboxylase, microinsulin, islet cell, islet antigen 2, and zinc transporter 8 autoantibodies
• Ab negative FDRs: Male and female adults 18-50 years old with a first degree relative (sibling, child, or parent) with T1D, who have tested negative for the above islet autoantibodies
• Ab + T1D Relatives: Male and females aged 12-50 years old with a first or second degree relative diagnosed with T1D, and testing positive for 1 of the above islet autoantibodies either at the screening visit, or through TrialNet screening obtained within the past 12 months.

Criteria for all subjects:

• BMI≤40 kg/m2 (If FDR is 40 kg/m2, the healthy control BMI can not exceed 45 kg/m2)
• HbA1c< 5.7%
• No medical history of diabetes.

Exclusion Criteria

• Any type of diabetes or hyperglycemia (HbA1c≥5.7%)
• Chronic illness or use of medications which interfere with glucose or islet hormone metabolism.
• Hemoglobin < 12 g/dL
• Presence of any psychiatric disorder that will affect the ability to participate in the study
• Pregnancy
• Severe milk or soy allergy that would disallow Boost® ingestion for MMTT
• Any condition that, in the judgment of the investigator, will adversely affect adequate participation in, or the safety or technical performance of the protocol.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Emily K. Sims

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Emily Sims

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana University

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

T1DFam

Identifier Type: -

Identifier Source: org_study_id