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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 背景资料： 对于无空腹高血糖的囊性纤维化相关糖尿病（CFRD）患者的治疗，尚无既定指南。管理包括餐前胰岛素给药，这对CF患者来说是一个重大负担。口服药物可以显著改善生活质量。然而，目前可用的代理商是不理想的面板堆石坝。 新型胰岛素促分泌剂瑞格列奈已开始在CFRD中进行研究。 其独特的药理学和药代动力学特性表明，它可能是在这种情况下的价值。 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，而不会引起低血糖。 目的： 1. 通过剂量递增研究，确定瑞格列奈控制餐后血糖而不诱发低血糖的最大剂量。 2. 系统比较口服瑞格列奈与当前“标准治疗”：标准化流质餐后皮下注射短效赖脯胰岛素。 研究设计和方法： 14名没有空腹高血糖的CFRD患者和7名对照者将进食流质食物。 CFRD受试者将接受以下研究条件之一：无餐前药物、赖脯胰岛素或瑞格列奈剂量递增。 对照受试者将接受不含餐前药物的流质餐。 将在基线时评估拟人和体格检查、炎症指数和代谢状态。将在进餐后按计划获得血糖、胰岛素、C肽和胰高血糖素测量值。 结束点： 终点为：进餐后240分钟葡萄糖和胰岛素的曲线下面积，以及葡萄糖、胰岛素、C-肽和胰高血糖素的其它参数响应进餐的变化。

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.