A MULTI-CENTER, PLACEBO-CONTROLLED, DOUBLE-BLINDED, RANDOMIZED STUDY OF DIABETE

该子项目是利用 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。 大多数囊性纤维化（CF）患者现在存活超过儿童期，由于胰岛素缺乏，CF相关糖尿病（CFRD）很常见。在25%的CF成人中发现了无空腹高血糖（FH）的CFRD，并与发病率和死亡率增加相关。 与糖耐量正常的CF患者相比，这些患者的BMI和肺功能恶化更快。 胰岛素缺乏会改变蛋白质和脂肪代谢，导致体重和瘦体重减轻，并导致肺部疾病和临床衰退。尽管胰岛素缺乏对蛋白质和脂肪代谢、体重和瘦体重有不利影响，但这些患者不常规使用外源性胰岛素治疗。 初步的同位素数据表明，胰岛素和口服降糖药瑞格列奈（程度较轻）可显著改善无FH的CFRD患者的蛋白质合成。 如果能证明胰岛素或瑞格列奈也能改善体重和肺功能，这将对成人CF患者的当前治疗和预后产生重大影响。 这些患者是否应该接受糖尿病治疗的问题在CFRD全国共识会议上被赋予了未来研究资金的最高优先权[1]。本研究的主要目的是确定胰岛素或增加内源性胰岛素分泌的口服糖尿病药物治疗是否会改善患有糖尿病但无空腹高血糖症的囊性纤维化患者的体重指数（BMI）和肺功能

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. The majority of cystic fibrosis (CF) patients now survive beyond childhood, and CF related diabetes (CFRD), due to insulin deficiency, is common. CFRD without fasting hyperglycemia (FH) is found in 25% of CF adults and is associated with increased morbidity and mortality. BMI and pulmonary function deteriorate much more rapidly in these patients than in CF patients with normal glucose tolerance. Insulin deficiency alters protein and fat metabolism resulting in loss of weight and lean body mass and contributing to pulmonary disease and clinical decline. These patients are not routinely treated with exogenous insulin despite the detrimental effects of insulin deficiency on protein and fat metabolism, weight, and lean body mass. Preliminary isotopic data have shown that insulin and, to a lesser extent, the oral diabetes agent repaglinide acutely improve protein synthesis in patients with CFRD without FH. If it can be shown that insulin or repaglinide also improves body mass and pulmonary function, it would have a major impact on the current therapy and prognosis for adult CF patients. The question of whether these patients should receive diabetes therapy was given the highest priority for future research funding at a national consensus conference on CFRD [1]. The primary objective of this research is to determine whether treatment with either insulin or an oral diabetes agent that increases endogenous insulin secretion will improve body mass index (BMI) and pulmonary function in cystic fibrosis patients who have diabetes without fasting hyperglycemia