Zaveri Swati, Stecenko Arlene, Hunt William R, Goss Amy, Sharma Puneet, Hartman Terryl J, Easley Kirk, Chandler Joshua D, Burley Tasha M, Driggers Chris, Ciccarella Amy, Zhou Heather, Narlow Kristen, Ziegler Thomas R, Daley Tanicia, Vellanki Priyathama, Alvarez Jessica
Division of Endocrinology, Metabolism, and Lipids; Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Division of Pulmonary, Asthma, Cystic Fibrosis, and Sleep; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
BMJ Open. 2024 Dec 26;14(12):e092503. doi: 10.1136/bmjopen-2024-092503.
People with cystic fibrosis (PwCF) are at high risk for developing cystic fibrosis (CF)-related diabetes (CFRD), which worsens morbidity and mortality. Although the pathological events leading to the development of CFRD are complex and not completely understood, dietary factors may play a role. For example, habitual intake of dietary added sugar (i.e., sugar not naturally occurring in foods) has been shown to be increased in PwCF and this excess intake of added sugar could increase the risk of CFRD.
METHODS AND ANALYSIS/DESIGN: The goal of this ongoing double-blind, randomised, parallel-group clinical trial is to recruit approximately 60 clinically stable adults with CF to determine if a low-added sugar intervention improves beta-cell responsiveness and insulin sensitivity (Aim 1), reduces visceral adipose tissue (VAT) and other ectopic fat deposition (Aim 2) and improves plasma redox status (Aim 3) over 8 weeks compared with a typical CF diet. All foods will be provided. Participant selection criteria include confirmed CF diagnosis without CFRD, ≥18 years of age, and baseline estimated daily total added sugar intake >16 tsp. Eligible participants will be randomised to one of two arms: a low-added sugar diet (<5% of kcal from added sugars) or a high-added sugar (≥13% kcal from added sugars) diet. The two diets will be isocaloric and provide 35%-40% kcal from fat. Participants will be seen in the research unit for a screening, baseline/randomisation and 4-week and 8-week follow-up visits. Major study endpoints are changes in beta-cell responsiveness determined by a glucose-potentiated arginine stimulation test (primary endpoint), VAT assessed by magnetic resonance imagin (MRI) and fasted plasma cysteine redox potential. Diet tolerance, body weight and compliance are monitored weekly by phone by an unblinded study dietitian. All analyses will be intention-to-treat. Changes in study endpoints will be assessed with repeated-measures analysis. Models will assess the effects by study arm, time on study, and the interaction between arm and time on study.
The National Institutes of Health (NIH) funds this study (R01 DK133523). The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 000004517). Any protocol modifications will be reviewed and approved by the IRB prior to implementation and communicated with the study team and participants, as relevant.We will provide reports of the findings to the NIH and Emory IRB in regular progress reports and post the findings on www.
gov. We will inform the findings of the study to the scientific community through presentations and peer-reviewed publications. Authorship for any resulting publications will follow the guidelines established by the International Committee of Medical Journal Editors.
This research study is registered at www.
gov (NCT05766774).
囊性纤维化患者（PwCF）患囊性纤维化相关糖尿病（CFRD）的风险很高，这会使发病率和死亡率恶化。尽管导致CFRD发生的病理事件很复杂且尚未完全了解，但饮食因素可能起一定作用。例如，已表明PwCF习惯性摄入的膳食添加糖（即食物中天然不存在的糖）有所增加，而这种过量摄入添加糖可能会增加患CFRD的风险。
方法与分析/设计：这项正在进行的双盲、随机、平行组临床试验的目标是招募约60名临床稳定的CF成年患者，以确定与典型CF饮食相比，低添加糖干预在8周内是否能改善β细胞反应性和胰岛素敏感性（目标1）、减少内脏脂肪组织（VAT）和其他异位脂肪沉积（目标2）以及改善血浆氧化还原状态（目标3）。所有食物将由试验提供。参与者选择标准包括确诊为CF但无CFRD、年龄≥18岁以及基线估计每日总添加糖摄入量>16茶匙。符合条件的参与者将被随机分为两组之一：低添加糖饮食（添加糖提供的热量<5%）或高添加糖饮食（添加糖提供的热量≥13%）。两种饮食将提供等热量，脂肪提供35%-40%的热量。参与者将在研究单位进行筛查、基线/随机分组以及4周和8周的随访。主要研究终点是通过葡萄糖增强精氨酸刺激试验确定的β细胞反应性变化（主要终点）、通过磁共振成像（MRI）评估的VAT以及空腹血浆半胱氨酸氧化还原电位。未盲法的研究营养师每周通过电话监测饮食耐受性、体重和依从性。所有分析将采用意向性分析。研究终点的变化将通过重复测量分析进行评估。模型将评估研究组、研究时间以及组与时间之间的相互作用的影响。
美国国立卫生研究院（NIH）资助本研究（R01 DK133523）。研究方案已获得埃默里机构审查委员会批准（IRB批准号：000004517）。任何方案修改将在实施前由IRB审查并批准，并在相关情况下与研究团队和参与者沟通。我们将在定期进展报告中向NIH和埃默里IRB提供研究结果报告，并将结果发布在www.clinicaltrials.gov上。我们将通过演讲和同行评审出版物向科学界通报研究结果。任何由此产生的出版物的作者身份将遵循国际医学杂志编辑委员会制定的指南。
