Pilot and Feasibility Study for the Treatment of Pre-diabetes in Patients With Cystic Fibrosis

The purpose of this study is to provide the necessary data and experience to design a larger, full scale clinical trial to determine if a certain medicine (repaglinide), which increases the amount of insulin secreted by the pancreas, can improve the nutritional status and pulmonary function of adolescents and young adults with cystic fibrosis and prediabetes by improving blood glucose control. The investigators are also trying to determine the relationship between systemic inflammatory factors and glucose impairment.

As people with Cystic Fibrosis (CF) are living well into adulthood new complications are arising. CF-Related Diabetes (CFRD) has emerged as a major complication. Years prior to the diagnosis of CFRD, patients have decreasing insulin secretion, glucose intolerance, deteriorating pulmonary function, and nutritional impairment. There are no current standard recommendations for the treatment of CF patients with prediabetes, and there is little evidence that treatment of this prediabetic state in CF patients will prevent the deterioration of the lung function, nutritional status and potentially slow the progression to manifest CFRD.

To determine the feasibility of testing this hypothesis, we will perform a pilot, double-blinded, randomized controlled trial in 20 CF pancreatic insufficient patients ages of 12 to 24 years old with impaired glucose tolerance test (IGT) or CFRD without fasting hyperglycemia (CFRD-No FH) and assign them to either placebo or Repaglinide 0.5 mg PO 3 - 4 times a day before meals for two years. Patients will monitor their blood glucose daily and will be followed every 3 months for 2 years to determine changes in nutritional status by BMI and DEXA, lung function tests, frequency of hospitalizations, antibiotic courses, and degree of glucose tolerance, insulin secretion and insulin sensitivity.

In addition, based on the evidence of increased inflammation in type 2 diabetes, correlation of systemic inflammatory response at different degrees of glucose tolerance and after treatment, will be assessed in these subjects, as well as in another 20 CF pancreatic insufficient matched patients with normal glucose tolerance who will be studied once without intervention

Eligibility Criteria:
Inclusion Criteria:

* Male or females 12 -24 years old
* Diagnosis of Cystic Fibrosis by sweat test with exocrine pancreatic insufficiency
* Must have a glucose pattern by Oral Glucose Tolerance Test with fasting blood glucose \<126 mg/dl and 2 hour: 140 - 199 mg/dl or \>200 mg/dl.
* Weight must be stable within 5% for 3 months prior to initiation visit
* Must be able to reproducibly perform spirometry based on American Thoracic Society guidelines

Exclusion Criteria:

* Patients receiving growth hormone therapy or taking insulin
* Patients with evidence of liver dysfunction
* Patients who are status-post lung or liver transplantation
* Patients who have received systemic steroids for more than 28 days during the 6 months prior to the study
* Patients with active ABPA on steroids
* Patients taking medications that affect glucose metabolism or contraindicated with repaglinide