Evaluation of the Enteroinsular Axis in Cystic Fibrosis
Children's Hospital of Philadelphia
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.
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…
Eligibility
- Age range
- 2+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria 1. Subjects age \>2y 2. Diagnosis of Cystic Fibrosis 3. 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) .
Interventions
- GeneticBlood 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.
Locations (2)
- The Children's Hopsital of PhiladelphiaPhiladelphia, Pennsylvania
- The University of PennsylvaniaPhiladelphia, Pennsylvania