WS16.05Impact of elexacaftor/tezacaftor/ivacaftor on glucose tolerance in adolescents with cystic fibrosis. Data from the MODUL-CF study

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.586

A.-S. Bonnel , A. Galderisi , L. Weiss , I. Sermet-Gaudelus , A. Besancon , A. Letierce , D. Sahki , Modul-CF Study Group

{"title":"WS16.05Impact of elexacaftor/tezacaftor/ivacaftor on glucose tolerance in adolescents with cystic fibrosis. Data from the MODUL-CF study","authors":"A.-S. Bonnel , A. Galderisi , L. Weiss , I. Sermet-Gaudelus , A. Besancon , A. Letierce , D. Sahki , Modul-CF Study Group","doi":"10.1016/j.jcf.2025.03.586","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>Highly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI), herald a new era in therapeutic strategy of cystic fibrosis (CF). ETI improves lung function and decreases recurrency of pulmonary infections. Its metabolic effects, including the impact on glucose tolerance and the risk for CF related diabetes (CFRD), remain controversial.</div></div><div><h3>Methods</h3><div>We investigated the effect of ETI on glucose tolerance in adolescents with CF (awCF) enrolled in the national French registry MODUL-CF. All the participants underwent a baseline oral glucose tolerance test (OGTT) before ETI initiation (M0) and at 12 months (M12). The cohort was stratified in two subgroups based on the baseline OGTT: normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) defined by impaired fasting glucose or impaired glucose tolerance or diabetes not requiring insulin treatment.</div></div><div><h3>Results</h3><div>We included 106 awCF (age 14.1 ± 1.5 years), 75 with NGT, 31 with AGT. The baseline characteristics of the two groups were similar except for a higher glucose level at 1-h and 2-h OGTT in the AGT group. ETI induced an increase in BMI z-score and in Forced Expiratory Volume in one second (p<0.001). After 12 months, awCF with NGT did not experience any change of 1-h and 2-h glucose. In contrast, awCF with AGT displayed a reduction of 2-h glucose at M12 (p=0.006). Fifteen awCF out of the 31 in the AGT group (48%) reversed to NGT whereas only 9/75 (17%) awCF in the NGT group progressed to AGT. The 3 participants with CFRD at baseline reversed to AGT. A 1-h glucose ≥ 8.7 mmol/L (157mg/dL) at baseline had 80% sensitivity to identify awCF with AGT at 12 months. A unitary increase of 1-h OGTT glucose at baseline increased by 1.51 [CI 1.20, 1.92] the risk of having AGT at 12-month ETI.</div></div><div><h3>Conclusion</h3><div>ETI improves glucose tolerance in awCF. One-hour glucose contributes to identify those at higher risk for AGT after 1 year of treatment.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S33"},"PeriodicalIF":5.4000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cystic Fibrosis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1569199325006824","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives

Highly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI), herald a new era in therapeutic strategy of cystic fibrosis (CF). ETI improves lung function and decreases recurrency of pulmonary infections. Its metabolic effects, including the impact on glucose tolerance and the risk for CF related diabetes (CFRD), remain controversial.

Methods

We investigated the effect of ETI on glucose tolerance in adolescents with CF (awCF) enrolled in the national French registry MODUL-CF. All the participants underwent a baseline oral glucose tolerance test (OGTT) before ETI initiation (M0) and at 12 months (M12). The cohort was stratified in two subgroups based on the baseline OGTT: normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) defined by impaired fasting glucose or impaired glucose tolerance or diabetes not requiring insulin treatment.

Results

We included 106 awCF (age 14.1 ± 1.5 years), 75 with NGT, 31 with AGT. The baseline characteristics of the two groups were similar except for a higher glucose level at 1-h and 2-h OGTT in the AGT group. ETI induced an increase in BMI z-score and in Forced Expiratory Volume in one second (p<0.001). After 12 months, awCF with NGT did not experience any change of 1-h and 2-h glucose. In contrast, awCF with AGT displayed a reduction of 2-h glucose at M12 (p=0.006). Fifteen awCF out of the 31 in the AGT group (48%) reversed to NGT whereas only 9/75 (17%) awCF in the NGT group progressed to AGT. The 3 participants with CFRD at baseline reversed to AGT. A 1-h glucose ≥ 8.7 mmol/L (157mg/dL) at baseline had 80% sensitivity to identify awCF with AGT at 12 months. A unitary increase of 1-h OGTT glucose at baseline increased by 1.51 [CI 1.20, 1.92] the risk of having AGT at 12-month ETI.

Conclusion

ETI improves glucose tolerance in awCF. One-hour glucose contributes to identify those at higher risk for AGT after 1 year of treatment.

查看原文本刊更多论文

elexaftor /tezacaftor/ivacaftor对青少年囊性纤维化患者糖耐量的影响。数据来自module - cf研究

目的高效的囊性纤维化（CF）调节剂，如elexexaftor /tezacaftor/ivacaftor (ETI)，预示着囊性纤维化（CF）治疗策略的新时代。ETI可以改善肺功能，减少肺部感染的复发。其代谢作用，包括对葡萄糖耐量的影响和CF相关性糖尿病（CFRD）的风险，仍然存在争议。方法：研究ETI对法国国家注册库module -CF中青少年CF （awCF）患者糖耐量的影响。所有参与者在ETI开始前（M0）和12个月时（M12）进行了基线口服葡萄糖耐量试验（OGTT）。该队列根据基线OGTT分为两个亚组：正常糖耐量（NGT）和异常糖耐量（AGT），由空腹血糖受损或糖耐量受损或不需要胰岛素治疗的糖尿病定义。结果awCF 106例（年龄14.1±1.5岁），NGT 75例，AGT 31例。除了AGT组在OGTT 1小时和2小时时血糖水平较高外，两组的基线特征相似。ETI诱导BMI z评分和用力呼气量在1秒内增加（p<0.001）。12个月后，NGT治疗的awCF 1-h和2-h血糖没有任何变化。相比之下，AGT awCF在M12时显示2小时葡萄糖减少（p=0.006）。AGT组31例awCF中有15例（48%）逆转为NGT，而NGT组只有9/75例（17%）awCF进展为AGT。基线时患有CFRD的3名受试者逆转为AGT。基线1小时血糖≥8.7 mmol/L (157mg/dL)， 12个月时诊断awCF与AGT的敏感性为80%。基线时1小时OGTT血糖的单一增加使12个月ETI时发生AGT的风险增加1.51 [CI 1.20, 1.92]。结论eti可改善awCF患者的葡萄糖耐量。治疗一年后，1小时血糖有助于识别AGT高危人群。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.