Please select the eligibility criteria that correspond to the clinical trial below.
Title: Determination of Beta-cell Responsiveness to the Incretin Hormones GLP-1 and GIP in Cystic Fibrosis
Brief Summary: In recent years, diabetes has emerged as one of the most significant co-diseases that many Cystic Fibrosis (CF) patients develop. Type 1 (T1D) and Type 2 (T2D) diabetes results when either the body does not make enough insulin or the body does not respond correctly to this insulin, respectively. Insulin is a hormone which is made by cells in the pancreas and helps carry glucose (sugar) from the food we eat to the cells of the body for energy. While cystic fibrosis related diabetes (CFRD) has many features similar to both T1D and T2D, patients with CF may not have the same symptoms as either T1D or T2D patients. Currently, there is little understanding of CFRD and the best options for treatment remain unclear.

The purpose of this research study is to examine and understand the various mechanisms that contribute to CFRD and gain a better understanding of potential means to treat CFRD. In particular, we plan to study the effects of incretin hormones that can enhance insulin production in CF patients.

Enrollment is complete for the protocol as initially written. In order to further study the role of the incretin hormone on Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function , we have received approval to extend our investigation to include the following study groups:

* Cystic Fibrosis participants with normal glucose tolerance
* Non-Cystic Fibrosis controls


Options:
A: 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.
B: Inclusion Criteria:

Inclusion Criteria for the Screening:

* Diagnosed cystic fibrosis
* Age 10 years and older

Inclusion Criteria for the therapeutic part of the study:

* Newly diagnosed Diabetes mellitus in the screening

Exclusion Criteria:

Exclusion Criteria for Screening:

* Diabetic keto-acidosis (blood glucose \> 350 mg/dl and arterial pH \< 7.25)
* Already treated Diabetes mellitus by oral antidiabetic medication or insulin

Exclusion Criteria for the therapeutic part of the study:

* Systemic steroid therapy during the last 3 months
* Transplantation (status post TX or on the waiting list for TX)
* Beginning pulmonary insufficiency, FEV1 \< 35% at pulmonary function test in stable condition
* Pregnancy
* Already diagnosed and treated diabetes mellitus
* Patients with diabetic keto-acidosis (blood glucose \> 350 mg/dl and arterial pH \< 7.25) with or without diabetic coma
* Severe liver insufficiency (chronic hepatitis B, AST or ALT twice the upper limit of normal, Quick's value \< 70% which is a contraindication to use Repaglinide)
* Treatment with an indispensable important drug which contraindicates Repaglinide
* PEG/ gastric tube/ total parenteral alimentation for more than 4 weeks during the study
* CF-patients with type 1 diabetes
* Not patient's consent to randomisation and therapeutic trial
* Participation on other medical trial
C: * Diabetic glucose pattern by oral glucose tolerance test (OGTT) of \>200 at 120 min. (stable and healthy at time of OGTT)
* Fasting glucose levels \<126.
* Weight stable within 5% in previous 3 months.
* Free from illness for two months.
* Male and female 16 and older, who are done growing
* Willing to come in for visits every 3 months.
* Patients receiving infrequent short bursts of systemic glucocorticoids may be considered for the study inclusion if: a. they have not received systemic glucocorticoids steroids for at least one month, b. they did not receive the steroids for more than 14 consecutive days or 28 days total in six months
D: Inclusion Criteria :

* Men or women 18 years and older.
* Diagnosis of CF documented.
* Obstructive ventilatory deficit light to moderate , as defined in the guidelines of the ATS / ERS , an FEV / FVC ratio \> 70% and ≥ 40% FEV .
* Stable health status, no episode of superinfection in the past 6 weeks.
* Impaired glucose tolerance , glucose \> 11.1 mmol / L at the 1st hour of the OGTT or unmedicated CFRD.
* Patients who wants to participate in an exercise program for 12 weeks.
* Sedentary (less than 105 min / week of physical activity ) .

Exclusion Criteria :

* Exacerbation of respiratory symptoms with or without hospitalization , or use of oral antibiotics in the last 6 weeks.
* Exacerbation with intravenous antibiotics .
* Severe obstructive deficit as defined by FEV \<40% , with an FEV / FVC ratio \<70 %.
* Any other disease or condition that may limit exercise performance .
* Without treatment with oral hypoglycemia , insulin, oral anti -inflammatory and other treatments that may influence glucose metabolism (patient under cortef accepted) .
* Hemoptysis ( \> 50-60 cc) in the last 6 weeks.
* Desaturation during exercise.

Answer: A