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

Completed

• Conditions: Type 1 Diabetes
• Interventions: Other: There is no intervention

• Registration Number: NCT04362917
• Lead Sponsor: Indiana University

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).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2017-11-14
• Study First Submitted: 2020-02-19
• Study First Submitted QC: 2020-04-23
• Study First Posted: 2020-04-27
• Primary Completion: 2021-08-27
• Study Completion: 2021-08-27
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-15
• Last Update Posted: 2023-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
FDR-	There is no intervention	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.
FDR+	There is no intervention	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.
Control	There is no intervention	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.

Primary Outcome Measures

Name	Time	Method
Measurement of beta cell function during the first phase of the first clamp procedure	The data for this analysis will come from cross-sectional samples collected through study completion, study completion will be on average 13-16 weeks from visit 1.	Our primary outcome is to assess if there is a difference in first phase beta call function in those genetically at risk for developing type 1 diabetes (first degree relatives) but who are islet autoantibody negative versus healthy controls with no family history of type 1 diabetes.; We will calculate the first phase beta cell function by multiplying the acute c-peptide response to glucose (ACPRg) (nmol/L) by the insulin sensitivity (M/I) (x10-5 mmol/kg/min per pmol/L)

Secondary Outcome Measures

Name	Time	Method
Measurement of beta cell function during of Second Phase of the first clamp procedure	The data for this analysis will come from cross-sectional samples collected through study completion, study completion will be on average 13-16 weeks from visit 1.	Our secondary outcome is to assess if there is a difference in second phase beta cell function in those genetically at risk for developing type 1 diabetes (first degree relatives) but who are islet autoantibody negative versus healthy controls with no family history of type 1 diabetes.; We will calculate the second phase beta cell function by averaging the C-peptide values collected during the steady state of the clamp (nmol\*L) and multiplying by the insulin sensitivity (M/I) (x10-5 mmol/kg/min per pmol/L)

Trial Locations

Locations (1)

Indiana University; 🇺🇸 Indianapolis, Indiana, United States