Genetics of Insulin and Incretins in Cystic Fibrosis
- Conditions
- Cystic Fibrosis
- Interventions
- Genetic: Blood or Saliva Sample Collection
- Registration Number
- NCT01852448
- Lead Sponsor
- Children's Hospital of Philadelphia
- Brief Summary
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 550
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Patients with Cystic Fibrosis Blood or Saliva Sample Collection Blood or saliva sample collection and medical record review.
- Primary Outcome Measures
Name Time Method Blood sample for DNA to genotype TCF7L2 and about 10 other GWAS-implicated T2DM genes. 1 day To examine the prevalence of GWAS-implicated T2DM alleles (including TCF7L2) across the spectrum of glucose abnormalities in children and adults with CF.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (2)
The Children's Hopsital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
The University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States