REPAGLINIDE AS A VIABLE ALTERNATIVE TO PRE-MEAL INSULIN IN CYSTIC FIBROSIS RE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: There are no established guidelines for treatment of patients with Cystic Fibrosis Related Diabetes (CFRD) without fasting hyperglycemia. Management consists of pre-meal insulin administration and represents a significant burden for CF patients. An oral agent could significantly improve quality of life. However, the currently available agents are not ideal for CFRD. The novel insulin secretagogue repaglinide has begun to be studied in CFRD. Its unique pharmacologic and pharmacokinetic properties suggest it may be of value in this setting. Hypothesis: Repaglinide can provide postprandial glycemic control comparable to injected insulin without causing hypoglycemia. Objectives: 1. To determine the maximum dose of repaglinide that can control postprandial glycemia without inducing hypoglycemia by performing a dose escalation study. 2. To systematically compare oral repaglinide to current "standard of care": subcutaneous short acting insulin lispro following a standardized liquid meal. Research Design and Methods: Fourteen patients with CFRD without fasting hyperglycemia and 7 controls will consume a liquid meal. One of the study conditions will be administered to CFRD subjects: no pre-meal medication, lispro insulin, or escalating repaglinide doses. Control subjects will receive the liquid meal without pre-prandial medication. Anthropomorphics and physical exam, indices of inflammation and metabolic status will be assessed at baseline. Plasma glucose, insulin, C-peptide, and glucagon measurements will be obtained as scheduled following meal administration. Endpoints: The endpoints will be: the area under the curve for glucose and insulin for 240 minutes following meal administration, and other parameters of glucose, insulin, C-peptide, and glucagon changes in response to meal.