Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology Pub Date : 2023-09-01 DOI:10.1016/j.jcte.2023.100320

Fabian Lurquin , Sophie Gohy , Michel P. Hermans , Vanessa Preumont

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引用次数: 3

Abstract

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 FEV₁, 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 vs 0.71±0.3U/kg/day; p = 0001). Total daily insulin dose decreased from 50±16 to 44±20U/day (p = 0.017). BMI improved (20.9 (IQR: 1.90) vs 22.1 kg/m² (IQR: 3.70); p = 0.014). HbA1c went from 7.3±1.1 to 7.7±1.6% (p = 0.072). 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) vs 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/m² (p = 0.047). HbA1c was unchanged (5.0±0.5%). FEV₁ improved in both groups (+11% and + 7% of predicted value; p < 0.001; p = 0.013).

Conclusion

Combined CFTR modulator therapies are correlated with a decrease in insulin doses and positive effects on BMI and FEV₁. HOMA indices did not change on tezacaftor + ivacaftor among CF patients without diabetes.

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联合CFTR调节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约有关

目的:联合CFTR调节剂治疗可显著改变囊性纤维化(CF)患者的肺预后。它们对葡萄糖代谢的影响需要进一步研究。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，以及非糖尿病CF患者HOMA指数的变化。方法回顾性分析17例CFRD患者tezacaftor + ivacaftor和elexaftor + tezacaftor + ivacaftor对FEV1、体重、BMI、HbA1c、每日胰岛素剂量的影响;15例非糖尿病CF患者tezacaftor + ivacaftor对HOMA指标的影响。结果CFRD组患者年龄为37±12岁(男性占70%)，F508del突变纯合子占88%。糖尿病病程15±10y。CFTR调节剂联合治疗的中位持续时间为16个月(IQR: 4) 13例患者接受tezacaftor + ivacaftor治疗，其中9例患者改为elexaftor + tezacaftor + ivacaftor。4例患者预先接受elexacaftor + tezacaftor + ivacaftor治疗。88%的患者胰岛素需求下降(0.85±0.3 vs 0.71±0.3 u /kg/天);p = 0001)。每日胰岛素总剂量由50±16 u /d降至44±20U/d (p = 0.017)。BMI改善(20.9 (IQR: 1.90) vs 22.1 kg/m2 (IQR: 3.70);p = 0.014)。HbA1c由7.3±1.1降至7.7±1.6% (p = 0.072)。无糖尿病的CF组(67%男性)中位年龄为22岁(IQR: 11)，其中93%为F508del突变纯合子。CFTR调节剂联合治疗时间为10±5个月。HOMA-B变化不显著(129.2 (IQR: 84.8) vs 103.5% (IQR: 66.3)， HOMA-S变化也不显著(从94±64到95±49%)。HOMA-BxS从112±45% (NS)降至104±29% (NS)。BMI由21.9±3 kg/m2上升至23.1±3.5 kg/m2 (p = 0.047)。HbA1c无变化(5.0±0.5%)。两组FEV1均改善(分别为预测值的+11%和+ 7%;p & lt;0.001;p = 0.013)。结论联合CFTR调节剂治疗可降低胰岛素剂量，对BMI和FEV1有积极影响。在非糖尿病的CF患者中，tezacaftor + ivacaftor对HOMA指标没有影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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