RecruitingNot ApplicableNCT01851694

Beta-cell Response to Incretin Hormones in Cystic Fibrosis

Determination of Beta-cell Responsiveness to the Incretin Hormones GLP-1 and GIP in Cystic Fibrosis

Sponsor

University of Pennsylvania

Enrollment

45 participants

Start Date

May 1, 2013

Study Type

INTERVENTIONAL

Conditions

Cystic Fibrosis Pancreatic Insufficiency

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

Eligibility

Min Age: 18 Years

Inclusion Criteria10

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.

Exclusion Criteria21

Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia (fasting glucose greater than126 mg/dL)
History of clinically symptomatic pancreatitis within last year
Prior lung or liver transplant
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)
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
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
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:
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.
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.
Inability to perform study specific procedures (MMTT, GPA).
subjects, who in study team opinion, may be non-compliant with study procedures.
elevation of serum amylase or lipase \> 1.5x ULN within 90 days of GPA test.