The Impact of Insulin Therapy on Protein Turnover in Pre-Diabetic CF Patients

胰岛素治疗对糖尿病前期 CF 患者蛋白质周转的影响

基本信息

批准号：
9115576
负责人：
Antoinette M. Moran
金额：
$ 69.2万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9115576
关键词：
Address Adult Affect Age Albumins American Beta Cell Body Weight Body Weight decreased Body mass index Catabolism Cells Cessation of life Childhood Clinical Consensus Controlled Clinical Trials Cystic Fibrosis Defect Deterioration Diabetes Mellitus Disease Dose Double-Blind Method Educational workshop Endocrine Fasting Fibrosis Foundations Functional disorder Health Hormones Hyperglycemia Individual Institutes Insulin Lung diseases Maintenance Malnutrition Methods Morbidity - disease rate National Institute of Diabetes and Digestive and Kidney Diseases Oxidative Stress Pancreas Pathologic Pathology Patients Pilot Projects Placebo Control Placebos Population Prediabetes syndrome Prevalence Proteins Protocols documentation Regimen Replacement Therapy Research Priority Respiratory physiology Role Severities Societies Therapeutic Transferrin Youth basal insulin clinical practice cystic fibrosis patients diabetic double-blind placebo controlled trial early cystic fibrosis glucose tolerance improved insulin secretion lean body mass lifetime risk loss of function mortality muscle form non-diabetic novel oxidative damage placebo controlled study protein degradation research study standard care sulfated glycoprotein 2 symposium

项目摘要

DESCRIPTION (provided by applicant): Insulin insufficiency related to pancreatic fibrosis and ß-cell dysfunction is present in almost every cystic fibrosis (CF) patient. Progressive abnormalities in insulin secretion begin in childhood, and, in adults, CF related diabetes (CFRD) is eventually present in more than half of the CF population. CFRD is associated with weight loss, protein catabolism, loss of lean body mass (LBM), and early death from lung disease and malnutrition. The negative consequences of diabetes are just the "tip of the iceberg", since clinical deterioration has been documented to begin in the pre-diabetic period. Non-diabetic glucose tolerance abnormalities in CF are associated with protein catabolism, weight loss and lung function decline, all of which correlate with the severity of insulin secretory defects, suggesting a key pathologic role for insulin insufficiency. Insulin is a potent anabolic hormone, critical for maintenance of body weight and muscle mass. In a placebo-controlled clinical trial, insulin therapy improved body mass index (BMI) and LBM in patients with very early CFRD (CFRD without fasting hyperglycemia), and this is now standard care for these patients. There is growing preliminary evidence that insulin therapy is beneficial even earlier, in CF patients with pre-diabetes due to insulin insufficiency. Given the universal prevalence of insulin insufficiency in CF, the high lifetime risk of developing diabetes, the clinical impact of insulin insufficiency n protein catabolism and survival in CF, and the critical importance of maintaining body weight and LBM in this population, there is an urgent need to determine whether insulin replacement therapy should be instituted for anabolic purposes prior to the actual onset of diabetes and, if so, to ascertain the optimal regimen. The current protocol describes a double-blind, placebo-controlled trial to determine whether insulin therapy improves protein catabolism in youth with CF and abnormal glucose tolerance, and to explore differences in efficacy between multiple daily pre-meal insulin dosing (as is currently standard for early CFRD) versus a more convenient once daily basal insulin dose (as has been used in small uncontrolled pilot studies). The findings of this study will provide a mechanistic rationale for instituting insulin in youth wih CF and pre-diabetes, and will inform both research studies and clinical practice as to the best regimen for insulin delivery in this population.

描述（适用提供）：几乎所有囊性纤维化（CF）患者都存在与胰腺纤维化和β细胞功能障碍有关的胰岛素不足。胰岛素分泌的进行性异常始于儿童期，在成年人中，与CF相关的糖尿病（CFRD）最终存在于CF人群的一半以上。 CFRD与体重减轻，蛋白质分解代谢，瘦体重（LBM）以及肺部疾病和营养不良的早期死亡有关。糖尿病的负面后果只是“冰山一角”，因为临床定义已记录在糖尿病前期开始。 CF的非糖尿病耐受性异常与蛋白质分解代谢，体重减轻和肺功能下降有关，所有这些都与胰岛素分泌缺陷的严重程度相关，这表明胰岛素不足的关键病理作用。代谢马龙，对于维持体重和肌肉质量至关重要。在一项安慰剂对照的临床试验中，胰岛素治疗改善了非常早期CFRD患者的体重指数（BMI）和LBM（CFRD而无需禁食高血糖），这现在是这些患者的标准护理。越来越多的初步证据表明，由于胰岛素不足，糖尿病患者的胰岛素治疗甚至更早。鉴于CF胰岛素不足的普遍流行，患糖尿病的终生风险很高，胰岛素不足N蛋白质的蛋白质分解及其CF的临床影响以及在该人群中保持体重和LBM的重要性最佳方案。当前的方案描述了一项双盲，安慰剂对照试验，以确定胰岛素治疗是否可以改善CF和异常葡萄糖耐受性的年轻人的蛋白质分解代谢，并探索多个日常膜前胰岛素剂量之间的效率差异（就像当前的早期CFRD一样），而每天的基础胰岛素次数更便宜）（曾经使用过的und shim）。这项研究的结果将为在青年CF和糖尿病前建立胰岛素提供机械原理，并将研究研究和临床实践提供有关该人群中胰岛素递送的最佳方案的信息。