Changes in glucose metabolism and metabolic outcomes following ETI initiation in patients with cystic fibrosis
Floor Bracquez, Aster Desouter, Stefanie Vincken, Eef Vanderhelst, Elke De Wachter, Alberto Papaleo, Robert HilbrandsAbstract
Background
Cystic fibrosis–related diabetes (CFRD) is a frequent complication in people with cystic fibrosis (pwCF). CFTR modulators such as Elexacaftor/Tezacaftor/Ivacaftor improve pulmonary outcomes, but their effect on glucose metabolism remains uncertain. This study evaluated changes in oral glucose tolerance after initiation of ETI.
Methods
In this uncontrolled retrospective single-center study, pwCF aged ≥10 years receiving ETI underwent a 2-hour oral glucose tolerance test before treatment, at 12 and 24 months. Participants were classified by baseline glucose tolerance: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CFRD. Secondary outcomes included changes in body weight, FEV1, lipids, and HbA1c.
Results
Of 68 pwCF (median age 23 years), 56% had NGT, 25% IGT, and 19% CFRD at baseline. Among 62 participants with OGTT data at baseline and 24 months, glucose tolerance remained stable in 48 (77%), improved in 10 (16%), and worsened in 4 (6%). Median HbA1c decreased from 5.5% to 5.3% (P<0.001). In 52 adults, median body weight increased by +7.3 kg (P<0.001). At year 1, pwCF with deteriorated OGTT showed a greater increase in total cholesterol compared with those with stable or improved OGTT (+26 vs. +5 mg/dL, P=0.008).
Conclusions
Glucose tolerance improved in some pwCF after ETI initiation, but responses were heterogeneous and improvements were not consistently sustained. A greater cholesterol increase in a small exploratory subgroup with worsening glucose tolerance requires confirmation.