Measurement of Beta Cell Death in Individuals With Cystic Fibrosis

Study Overview
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Brief Summary
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This study evaluates the feasibility of using differentially methylated insulin DNA, a biomarker of beta cell death, in determining the time course of beta cell death and development of diabetes in people with cystic fibrosis. Study participants with cystic fibrosis and healthy control participants will have a blood sample drawn in order to measure the levels of differentially methylated insulin DNA.

Detailed Description
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Cystic fibrosis related diabetes (CFRD) causes increased morbidity and mortality in people with cystic fibrosis (CF). The prevalence of CFRD increases with age. While CFRD is diagnosed in only 2 percent of children under 10 year sof age, it is present in 19 percent of adolescents and up to 50 percent of adults with CF. Although CFRD is uncommon in children, recent animal and human studies have shown that milder glycemic abnormalities are common in infants and young children with CF. One of the proposed mechanisms for early glucose dysregulation in CF is related to ongoing beta cell death that may start at a very early age. The assay to be used in this study measures differentially methylated insulin DNA, released exclusively by beta cells, to determine levels of beta cell death. This assay has been shown to detect beta cell death in individuals at risk of developing type 1 diabetes. If this assay successfully detects beta cell death in individuals with CF, the investigators can identify critical time points of beta cell loss in people with CF. Understanding how and when glycemic dysregulation occurs in CF will lead to better treatment of CFRD in the future.

Official Title
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Measurement of Beta Cell Death in Individuals With Cystic Fibrosis

Conditions
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Cystic Fibrosis-related Diabetes

Intervention / Treatment
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* Diagnostic Test: Measurement of differentially methylated insulin DNA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Cystic Fibrosis Subjects: Age 0 - 21 years Diagnosis of CF by two CF-causing mutations or elevated sweat chloride test Normal glucose tolerance, impaired glucose tolerance, indeterminate glucose tolerance or CFRD Pancreatic insufficiency Exclusion Criteria for Cystic Fibrosis Subjects: Age > 21 years Diagnosis of type 1 or type 2 diabetes Pregnancy Oral or IV steroid use in the past 2 weeks Pulmonary exacerbation requiring hospital admission in the past 2 weeks. Initiation of CFTR corrector or potentiator medication within 6 months Inclusion Criteria for healthy, age-matched controls: Age 0 - 21 years Exclusion Criteria for healthy, age-matched controls: Age > 21 years Diagnosis of type 1 or type 2 diabetes or pre-diabetes Disorders impacting pancreatic exocrine function Pregnancy Oral or IV steroid use in the past 2 weeks

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cystic Fibrosis<br>Serum sample will be drawn once | Diagnostic Test: Measurement of differentially methylated insulin DNA<br>* A serum sample will be drawn to measure differentially methylated insulin DNA.<br>|
| Healthy, age-matched controls<br>Serum sample will be drawn once | Diagnostic Test: Measurement of differentially methylated insulin DNA<br>* A serum sample will be drawn to measure differentially methylated insulin DNA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of differentially methylated insulin DNA from infancy to early adulthood in people with cystic fibrosis | Levels of differentially methylated insulin DNA in people with CF from infancy to young adulthood will be measured and compared to levels in healthy, age-matched controls. | Level to be drawn once, usually within 3 months of recruitment into study. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between level of differentially methylated insulin DNA and oral glucose tolerance status in people with CF. | Levels of differentially methylated insulin DNA in adolescents and young adults with CF will be correlated with oral glucose tolerance status such as impaired glucose tolerance, indeterminate glucose tolerance and CFRD. | Level to be drawn once, usually within 3 months of recruitment into study. | 
| Correlation between level of differentially methylated insulin DNA and use of CFTR modulator therapy. | Measure differences in levels of differentially methylated insulin DNA in people with CF on CFTR modulator drugs and people with CF not on modulator therapy. | Level to be drawn once, usually within 3 months of recruitment into study. |