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| Name | Class |
|---|---|
| Juvenile Diabetes Research Foundation | OTHER |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| There is no intervention | Other | There is no intervention |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Inclusion criteria for each subject group* note age limits different for each group*:
Criteria for all subjects:
Exclusion criteria for all participants:
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Comparing a population at risk for T1D to healthy controls.
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| Name | Affiliation | Role |
|---|---|---|
| Emily Sims | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University | Indianapolis | Indiana | 46202 | United States |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| 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. |
| 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. |
| 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. |
| 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. |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |