Genetics of Insulin and Incretins in Cystic Fibrosis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Blood or Saliva Sample Collection.
- Who it may be relevant to
- Registry conditions: Cystic Fibrosis. Basic parameters: from 2 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Evaluation of the Enteroinsular Axis in Cystic Fibrosis
Overview
Cystic fibrosis related diabetes (CFRD) is associated with worse CF-relevant outcomes. The mechanisms underlying CFRD development are not fully understood, but recent evidence suggests Type 2 Diabetes Mellitus (T2DM) mechanisms may be involved and may involve incretins (gut secreted hormones that augment insulin secretion in response to a nutrient load). This study will examine the prevalence of Genome wide association study (GWAS)-implicated T2DM alleles (including TCF7L2) across the spectrum of glucose abnormalities in CF and will use this information to compare incretin and insulin secretion in non-diabetic children and adults with high risk and low risk alleles.
Detailed description
CFRD is associated with worse nutritional status, greater pulmonary function decline, and increased mortality, highlighting its relevance in CF and arises primarily from compromised insulin secretion--traditionally considered a by-product of pancreatic exocrine tissue damage and fibrosis. Recent developments in the field of diabetes are propelling a re-examination of this basic explanation. Genome-wide association studies have associated genetic variants in TCF7L2, a transcription factor implicated in enteroendocrine function, with increased susceptibility to T2DM and CFRD.
The Objectives of this study are to perform targeted sequencing of TCF7L2 and other GWAS-associated T2DM genes in the pediatric and adult CF populations and then to compare insulin secretory capacity, β-cell sensitivity to glucose, and incretin secretion in non-diabetic CF subjects with high and low-risk alleles.
Phase 1 will include 450-500 subjects (Children age\>= 2 years, adolescents, and adults) for TCF7L2 genotype and ten other GWAS-implicated T2DM genes. The distribution of TCF7L2 and other GWAS-implicated T2 DM genes across the spectrum of glucose abnormalities will be described. Phase 1 requires a single blood or saliva sample and review of medical records.
Interventions
- Genetic Blood or Saliva Sample Collection
A blood or saliva sample will be obtained for genotyping of TCF7L2 and approximately ten other genes implicated in type 2 diabetes.
Primary outcome measures
- Blood sample for DNA to genotype TCF7L2 and about 10 other GWAS-implicated T2DM genes. [Time frame: 1 day]
Eligibility criteria
Inclusion criteria
- Subjects age >2y
- Diagnosis of Cystic Fibrosis
- For subjects< 18 years, parental/guardian permission (informed consent) and if appropriate, child assent
Exclusion Criteria 1. Established diagnosis of non-CFRD (cystic fibrosis related diabetes) (e.g T1DM)
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Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
United States · 2 centers
- The Children's Hopsital of Philadelphia — Philadelphia
- The University of Pennsylvania — Philadelphia
Identifiers
NCT: NCT01852448 · 12-009589