This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Cystic fibrosis-related diabetes (CFRD) has emerged as a major complication, shortening survival and increasing morbidity as patients with CF are living into adulthood. Years prior to the diagnosis of CFRD patients have decreasing insulin secretion, glucose intolerance, deteriorating pulmonary function, and nutritional impairment. However, there is lack of evidence that treatment of this prediabetic state will prevent the deterioration of the lung function, nutritional status and potentially slow the progression to manifest CFRD. To test this hypothesis, we will perform a pilot, double-blinded, randomized controlled trial in 20 CF patients ages of 12 and 22 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 before meals for two years. Nutritional assessment, pulmonary function tests, inflammatory markers and determination of glucose tolerance, insulin secretion and insulin sensitivity will be performed at baseline and every three months. In addition, based on the evidence of increased inflammation in type 2 diabetes, correlation of systemic inflammatory response at different degrees of glucose tolerance impairment and after treatment will also be assessed in these subjects and in another 20 CF patients with normal glucose tolerance that will be studied once without intervention.If successful, the findings of such a trial will be novel, may determine the importance of considering early treatment of glucose impairment during the pre-diabetic state in CF and may generate new approaches on the current standards of care and prognosis of CF patients.
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