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

Type 1 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04362917
• Other study ID #: T1DFam
• Status: Completed
• Start date: November 14, 2017
• Est. completion date: August 27, 2021

Study information

• Verified date: March 2023
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: August 27, 2021
• Est. primary completion date: August 27, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 55 Years

Eligibility

Inclusion criteria for each subject group* note age limits different for each group*:

• 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 for all participants:

• 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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Other:
• There is no intervention
There is no intervention

Locations

Country	Name	City	State
United States	Indiana University	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Measurement of the Unmethylated and methylated DNA as this is a marker of beta cell death	Another prespecified outcome measure is to see if there is a difference in unmethylated/methylated INS DNA (which is a biomarker of beta cell death) 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.	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.
Other	Measurement of the Fasting Proinsulin to the C-peptide ratio (PI:C)	Another prespecified outcome measure is to see if there is a difference in the Proinsulin/C-peptide ratio (PI:C) 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.	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.
Other	Test-retest variability of the above mentioned variables (first phase, second phase, Unmethylated and methylated DNA, fasting PI:C	We will calculate the test-retest variability of the above mentioned variables (first phase, second phase, unmethylated/methylated DNA, fasting proinsulin/c-peptide), by looking at the between-visit coefficients of variation and intraclass correlations.	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.
Primary	Measurement of beta cell function during the first phase of the first clamp procedure	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)	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.
Secondary	Measurement of beta cell function during of Second Phase of the first clamp procedure	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)	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.