Evaluation of Insulin Secretion and Continuous Glucose Monitoring in Patients with Cystic Fibrosis After Initiation of Transmembrane Conductance Regulator Modulator: A 52-Week Prospective Study

Introduction: Limited studies have explored the impact of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators on glucose tolerance and insulin secretion in patients with CF, yielding varied results. This study aims to assess alterations in glucose metabolism and insulin secretion over 24 and 52 weeks following CFTR modulator initiation in a cohort of pediatric and adult patients with CF. Materials and Methods: A prospective longitudinal study conducting oral glucose tolerance test (OGTT) with C-peptide and insulin levels. The insulin secretion rate at 60 min (ISR60) and the insulinogenic index (IGI) were calculated during the first 60 and 30 min of the OGTT, respectively. Glucose metabolism status was categorized as normal (NGT), indeterminate (INDET), impaired glucose tolerance (IGT), or cystic fibrosis-related diabetes (CFRD). Additionally, continuous glucose monitoring (CGM) was performed for 14 days at each visit. We employed a repeated-measures general linear model to assess changes in insulin secretion and CGM metrics, with glucose tolerance status as the between-subjects factor and visit (baseline, 24 and 52 weeks) as the within-subjects factor. Results: The study comprised 25 patients (11 adults and 14 pediatrics). At baseline, 2 patients (8%) had NGT, 8 (32%) had INDET, 10 (40%) had IGT, and 5 (20%) had CFRD. Overall, there were no significant changes in insulin and C-peptide area under the curve (AUC), IGI and DI after 52 weeks. However, we observed an increase in ISR60 among NGT patients (mean change: 1.766; 95% CI: 1.414; 2.118, p < 0.001). Consistently, average glucose exhibited a significant decrease in NGT patients between 24 and 52 weeks (mean change: -5.645; 95% CI: -4.233; -10.866, p = 0.028). Conclusions: Treatment with CFTR modulators potentially enhances insulin secretion in patients with CF NGT. Early initiation of treatment, as evaluated through long-term prospective trials, is essential to further investigate whether decreased glucose control is preventable or reversible.