联合CFTR调节剂疗法与囊性纤维化相关糖尿病的合成代谢益处和胰岛素节省作用相关。
Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes.
作者信息
Lurquin Fabian, Gohy Sophie, Hermans Michel P, Preumont Vanessa
机构信息
Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium.
Department of Pneumology, CF Reference Center, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium.
出版信息
J Clin Transl Endocrinol. 2023 Jun 24;33:100320. doi: 10.1016/j.jcte.2023.100320. eCollection 2023 Sep.
AIMS
Combined CFTR modulator therapies have dramatically altered pulmonary outcomes in patients with cystic fibrosis (CF). Their impact on glucose metabolism requires further investigations. This study aims to evaluate insulin requirements after initiation of combined CFTR modulator therapy in patients with CF-related diabetes (CFRD) and HOMA indices changes in CF patients without diabetes.
METHODS
We retrospectively analyzed: 1) the effects of tezacaftor + ivacaftor and elexacaftor + tezacaftor + ivacaftor on FEV, weight, BMI, HbA1c, and daily insulin dose, in 17 CFRD patients and 2) the impact of tezacaftor + ivacaftor on HOMA indices in 15 CF patients without diabetes.
RESULTS
Age was 37±12y in the CFRD group (70% men), 88% of whom were homozygous for F508del mutation. Diabetes duration was 15±10y. Median duration of combined CFTR modulator therapy was 16 months (IQR: 4) Thirteen patients received tezacaftor + ivacaftor, of whom 9 were switched to elexacaftor + tezacaftor + ivacaftor. Four patients received elexacaftor + tezacaftor + ivacaftor up front. A decrease in insulin needs was noticed in 88% of patients (0.85±0.3 0.71±0.3U/kg/day; ). Total daily insulin dose decreased from 50±16 to 44±20U/day (). BMI improved (20.9 (IQR: 1.90) 22.1 kg/m (IQR: 3.70); ). HbA1c went from 7.3±1.1 to 7.7±1.6% (). Median age was 22y (IQR: 11) in the CF group without diabetes (67% men), 93% of whom were homozygous for F508del mutation. Duration of combined CFTR modulator therapy was 10±5 months. HOMA-B changes were not significant (129.2 (IQR: 84.8) 103.5% (IQR: 66.3) nor were HOMA-S changes (from 94±64 to 95±49%). HOMA-BxS decreased from 112±45 to 104±29% (NS). BMI rose from 21.9±3 to 23.1±3.5 kg/m (). HbA1c was unchanged (5.0±0.5%). FEV improved in both groups (+11% and + 7% of predicted value; ; ).
CONCLUSION
Combined CFTR modulator therapies are correlated with a decrease in insulin doses and positive effects on BMI and FEV. HOMA indices did not change on tezacaftor + ivacaftor among CF patients without diabetes.
目的
联合使用囊性纤维化跨膜传导调节因子（CFTR）调节剂疗法显著改善了囊性纤维化（CF）患者的肺部预后。其对葡萄糖代谢的影响尚需进一步研究。本研究旨在评估CF相关糖尿病（CFRD）患者开始联合CFTR调节剂治疗后的胰岛素需求，以及无糖尿病的CF患者的稳态模型评估（HOMA）指数变化。
方法
我们进行了回顾性分析：1）在17例CFRD患者中，评估替扎卡福+依伐卡托以及依列卡福+替扎卡福+依伐卡托对第一秒用力呼气容积（FEV）、体重、体重指数（BMI）、糖化血红蛋白（HbA1c）和每日胰岛素剂量的影响；2）在15例无糖尿病的CF患者中，评估替扎卡福+依伐卡托对HOMA指数的影响。
结果
CFRD组患者年龄为37±12岁（70%为男性），其中88%为F508del突变纯合子。糖尿病病程为15±10年。联合CFTR调节剂治疗的中位持续时间为16个月（四分位间距：4）。13例患者接受替扎卡福+依伐卡托治疗，其中9例换用依列卡福+替扎卡福+依伐卡托。4例患者一开始就接受依列卡福+替扎卡福+依伐卡托治疗。88%的患者胰岛素需求减少（从0.85±0.3降至0.71±0.3U/kg/天）。每日胰岛素总剂量从50±16U/天降至44±20U/天。BMI有所改善（从20.9（四分位间距：1.90）升至22.1kg/m²（四分位间距：3.70））。HbA1c从7.3±1.1%升至7.7±1.6%。无糖尿病的CF组患者中位年龄为22岁（四分位间距：11）（67%为男性），其中93%为F508del突变纯合子。联合CFTR调节剂治疗的持续时间为10±5个月。HOMA-β变化不显著（从129.2（四分位间距：84.8）降至103.5%（四分位间距：66.3）），HOMA-IS变化也不显著（从94±64降至95±49%）。HOMA-β×S从112±45降至104±29%（无统计学意义）。BMI从21.9±3升至23.1±3.5kg/m²。HbA1c无变化（5.0±0.5%）。两组患者的FEV均有所改善（分别提高至预测值的+11%和+7%）。
结论
联合CFTR调节剂疗法与胰岛素剂量减少以及对BMI和FEV的积极作用相关。在无糖尿病的CF患者中，替扎卡福+依伐卡托治疗后HOMA指数未发生变化。
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