Background

Cystic fibrosis related diabetes (CFRD) is associated with pulmonary decline and compromised nutritional status. Emerging data suggest that CFTR dysfunction may play a direct role in the pathogenesis of CFRD; however, studies investigating the effect of CFTR modulators on glycemic outcomes in patients with cystic fibrosis (CF) have shown mixed results. The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on glycemic control is currently unknown. Our objective was to investigate the effect of ETI initiation on glycemia in adults with CF using continuous glucose monitoring (CGM).

Methods

In this prospective observational study, 34 adults with CF and at least one F508del CFTR mutation wore CGM sensors for 14 days prior to starting ETI and again 3-12 months after ETI initiation. Hypoglycemia symptoms were queried at each visit, and most recent anthropometric measures and spirometry data were obtained by chart review.

Results

Twenty-three participants completed the study. Compared to baseline, average glucose (AG), standard deviation (SD), % time >200 mg/dL, and peak sensor glucose decreased with ETI treatment, and % time in target range 70-180 mg/dL increased. Improvements in glycemic parameters were most notable in individuals with CFRD. There was no significant change in CGM-measured or self-reported hypoglycemia before and after ETI initiation.

Conclusion

Initiation of ETI in adults with CF was associated with improvement CGM-derived measures of hyperglycemia and glycemic variability with no effect on hypoglycemia. Further studies are needed to investigate underlying etiology of these changes and the long-term impact of ETI on glycemic control in patients with CF.

中文翻译：

---

elexacaftor/tezacaftor/ivacaftor (ETI) 对囊性纤维化成人血糖的影响

背景

囊性纤维化相关糖尿病 (CFRD) 与肺功能衰退和营养状况受损有关。新出现的数据表明 CFTR 功能障碍可能在 CFRD 的发病机制中发挥直接作用；然而，调查 CFTR 调节剂对囊性纤维化 (CF) 患者血糖结果影响的研究显示了不同的结果。elexacaftor-tezacaftor-ivacaftor (ETI) 对血糖控制的影响目前尚不清楚。我们的目标是使用连续血糖监测 (CGM) 研究 ETI 启动对成人 CF 患者血糖的影响。

方法

在这项前瞻性观察研究中，34 名患有 CF 和至少一个 F508del CFTR 突变的成年人在开始 ETI 之前佩戴 CGM 传感器 14 天，并在 ETI 开始后 3-12 个月再次佩戴。每次就诊时询问低血糖症状，并通过图表审查获得最新的人体测量和肺活量测量数据。

结果

二十三名参与者完成了研究。与基线相比，平均葡萄糖 (AG)、标准差 (SD)、>200 mg/dL 的时间百分比和峰值传感器葡萄糖随着 ETI 治疗而降低，目标范围 70-180 mg/dL 的时间百分比增加。CFRD 患者的血糖参数改善最为显着。在 ETI 启动前后，CGM 测量或自我报告的低血糖没有显着变化。

结论

在患有 CF 的成人中启动 ETI 与改善 CGM 衍生的高血糖和血糖变异性测量相关，但对低血糖没有影响。需要进一步的研究来调查这些变化的潜在病因以及 ETI 对 CF 患者血糖控制的长期影响。