Incretin HormonesBeta-cell Response to Incretin Hormones in Cystic Fibrosis

Inclusion Criteria:

1. Confirmed diagnosis of cystic fibrosis, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria,
2. Age greater than or equal to 18y on date of consent
3. Pancreatic insufficiency
4. Recent OGTT consistent with Indeterminate-GT, IGT, CFRD w/o fasting hyperglycemia, or an established diagnosis of CFRD without fasting hyperglycemia
5. For female subjects, negative urine pregnancy test at enrollment.

Control Subjects:

1. No history of cystic fibrosis.
2. Age ≥ 18y on date of consent.
3. Recent OGTT consistent with NGT.
4. For female subjects, negative urine pregnancy test at enrollment.

Exclusion Criteria:

1. Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia (fasting glucose greater than126 mg/dL)
2. History of clinically symptomatic pancreatitis within last year
3. Prior lung or liver transplant
4. Severe CF liver disease, as defined by portal hypertension
5. Fundoplication-related dumping syndrome
6. Medical co-morbidities that are not CF-related or are unstable per investigator opinion (i.e. history of bleeding disorders, immunodeficiency)
7. Acute illness or changes in therapy (including antibiotics) within 6 weeks prior to study procedures
8. Treatment with oral or intravenous corticosteroids within 6 weeks of study
9. Hemoglobin less than10g/dL, within 90 days of Visit 1 or at Screening
10. Abnormal renal function, within 90 days of Visit 1 or at Screening; defined as Creatinine greater than 2x upper limit of normal (ULN) or potassium greater than 5.5mEq/L on non-hemolyzed specimen
11. Inability to perform study specific procedures (MMTT, GPA)
12. Subjects, who in study team opinion, may be non-compliant with study procedures.

Control Subjects who will be exposed to GIP only:

1. History of clinically symptomatic pancreatitis.
2. History of liver disease.
3. History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk to the subject.
4. Hemoglobin <10g/dL, within 90 days of GPA test or at Screening.
5. Abnormal renal function, within 90 days of GPA test or at Screening; defined as creatinine > 2x upper limit of normal (ULN) or potassium > 5.5mEq/L on non-hemolyzed specimen.
6. Inability to perform study specific procedures (MMTT, GPA).
7. subjects, who in study team opinion, may be non-compliant with study procedures.
8. elevation of serum amylase or lipase > 1.5x ULN within 90 days of GPA test.