Beta-cell Response to Incretin Hormones in Cystic Fibrosis

Prior treatment

• Prior lung or liver transplant
• Acute illness or changes in therapy (including antibiotics) within 6 weeks prior to study procedures
• Treatment with oral or intravenous corticosteroids within 6 weeks of study

Other illness

• History of clinically symptomatic pancreatitis within last year
• Severe CF liver disease, as defined by portal hypertension
• Fundoplication-related dumping syndrome
• Medical co-morbidities that are not CF-related or are unstable per investigator opinion (i.e. history of bleeding disorders, immunodeficiency)
• History of clinically symptomatic pancreatitis.
• History of liver disease.
• 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.

Lab values

• Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia (fasting glucose greater than126 mg/dL)
• Hemoglobin less than10g/dL, within 90 days of Visit 1 or at Screening
• 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
• Hemoglobin \<10g/dL, within 90 days of GPA test or at Screening.
• 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.
• elevation of serum amylase or lipase \> 1.5x ULN within 90 days of GPA test.

Other

• Inability to perform study specific procedures (MMTT, GPA)
• Subjects, who in study team opinion, may be non-compliant with study procedures.
  • Control Subjects who will be exposed to GIP only:
• Inability to perform study specific procedures (MMTT, GPA).
• subjects, who in study team opinion, may be non-compliant with study procedures.

• Confirmed diagnosis of cystic fibrosis, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria,
• Age greater than or equal to 18y on date of consent
• Pancreatic insufficiency
• Recent OGTT consistent with Indeterminate-GT, IGT, CFRD w/o fasting hyperglycemia, or an established diagnosis of CFRD without fasting hyperglycemia
• For female subjects, negative urine pregnancy test at enrollment.
  • Control Subjects:
• No history of cystic fibrosis.
• Age ≥ 18y on date of consent.
• Recent OGTT consistent with NGT.
• For female subjects, negative urine pregnancy test at enrollment.