P-281: Metabolic and nutritional effects of CFTR modulator therapy (ETI) in cystic fibrosis: a stratified analysis by genotype and CFRD status
G da Costa Oliveira, F Faganello Colombo, T Altarejo Marin, L Trevisan Carvalho, D de Souza Paiva Borgli, A Fernando Ribeiro, A C Gonçalves, J D Ribeiro, M Zorron Mei Hsia PuAbstract
Introduction
Cystic fibrosis-related diabetes (CFRD) is the most common endocrine-metabolic comorbidity in cystic fibrosis (CF), resulting from progressive insulin deficiency due to beta-cell dysfunction, chronic inflammation, and insulin resistance. The introduction of elexacaftor/tezacaftor/ivacaftor (ETI) has improved pulmonary and nutritional outcomes, but its metabolic effects, especially on glycemic control, remain heterogeneous.
Objectives
To evaluate changes in glycated hemoglobin (HbA1c) and body mass index (BMI) before and after 6 months of ETI therapy in CF patients, stratified by glycemic status and genotype.
Methods
This longitudinal observational study included CF patients from a reference center. BMI and HbA1c were assessed at baseline and after 6 months of ETI therapy. Patients were stratified into CFRD, pre-diabetes, and no CFRD groups. Genotypes were classified as homozygous, heterozygous for minimal function mutations, or heterozygous for residual function mutations.
Results
CFRD patients had higher baseline HbA1c. After ETI, HbA1c decreased in the CFRD group (6.0% to 5.4%), remained stable in pre-diabetes (5.97%), and slightly decreased in non-CFRD patients (5.45% to 5.35%). BMI increased markedly in the CFRD group (14.8 to 19.1 kg/m2), slightly in non-CFRD (16.5 to 16.7 kg/m2), and remained stable in pre-diabetes (19.0 to 18.7 kg/m2).
Conclusions
ETI was associated with improved nutritional status, particularly in CFRD patients, and may improve glycemic control in those with higher baseline HbA1c. The heterogeneous response underscores the need for individualized metabolic monitoring in cystic fibrosis.