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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景： 对于无空腹高血糖的囊性纤维化相关性糖尿病(CFRD)患者，目前尚无明确的治疗指南。管理包括餐前胰岛素注射，这对CF患者来说是一个巨大的负担。口服制剂可以显著提高生活质量。然而，目前可用的代理并不是CFRD的理想选择。 新型胰岛素促分泌剂瑞格列奈已开始在CFRD进行研究。其独特的药理和药代动力学特性表明，它在这种情况下可能有价值。 假设： 瑞格列奈可以提供与注射胰岛素相当的餐后血糖控制，而不会导致低血糖。 目标： 1.通过剂量递增研究，确定在不引起低血糖的情况下控制餐后血糖的瑞格列奈的最大剂量。 2.系统地比较口服瑞格列奈和目前的“护理标准”：标准化液体餐后皮下短效胰岛素利普罗。 研究设计与方法： 14名无空腹高血糖的CFRD患者和7名对照组将摄入流质餐。其中一项研究条件将应用于CFRD受试者：不使用餐前药物，不使用利普罗胰岛素，或增加瑞格列奈的剂量。对照受试者将接受不含餐前药物的流质餐。 人体形态和体格检查、炎症和代谢状态指数将在基线时进行评估。餐后如期检测血糖、胰岛素、C-肽和胰高血糖素。 终端： 终点是：餐后240分钟内血糖和胰岛素曲线下的面积，以及血糖、胰岛素、C肽和胰升糖素随餐后变化的其他参数。

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.