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.
Name: Blood or Saliva Sample Collection
Name: Glucose -potentiated arginine (GPA) stimulation tests
Description: To examine the prevalence of GWAS-implicated T2DM alleles (including TCF7L2) across the spectrum of glucose abnormalities in children and adults with CF.Measure: Blood sample for DNA to genotype TCF7L2 and about 10 other GWAS-implicated T2DM genes. Time: 1 day
Description: Pancreatic ß-cell function will be evaluated using the GPA test which can be used to measure β-cell secretory capacity and sensitivity to glucose.Measure: Glucose-Potentiated Arginine Stimulation Test (GPA test) Time: 1 day
Description: Incretin and insulin secretion as well as glucose tolerance will be assessed using the MMTT.Measure: Mixed Meal Tolerance Testing (MMTT) Time: 1 day
There is one SNP
SECOND PHASE OF STUDY: Inclusion Criteria 1. Subjects age >8y 2. Diagnosis of Cystic Fibrosis 3. pancreatic insufficient 4. negative urine pregnancy test at enrollment 5. TCF7L2 rs7903146 genotype of T/T or C/C 6.