2469-P: Insulin Secretion Trends in Cystic Fibrosis (CF) in the Pre- and Post-CFTR Modulator Era

Introduction and Objective: Advanced cystic fibrosis transmembrane conductance regulator (CFTR) modulators such as elexacaftor-tezacaftor-ivacaftor (ETI) have transformed outcomes in people with CF (pwCF). Their effect on the natural history of glucose intolerance remains unclear. We evaluated longitudinal changes in insulin secretion and sensitivity by leveraging 3-hr frequently sampled oral glucose tolerance tests (fsOGTT) collected across two studies in pwCF (GEM-CF and EnVision-GT, 2016-2023). Methods: We conducted a secondary retrospective analysis of fsOGTTs including glucose and insulin. Longitudinal changes in insulin secretion were compared pre- vs post-ETI initiation with the following estimates: insulinogenic index (IGI), insulin:glucose incremental area under the curve (iAUC) within 30 min (iAUC30) and 180 min (iAUC180). Matsuda index was used to estimate insulin sensitivity and was used derive the oral disposition index (oDI). Analysis used mixed-effects models to account for within-participant correlation of repeat measures. Results: 13 participants had ≥2 fsOGTTs pre-ETI and at least ≥1 fsOGTT post-ETI. Median age=10.8 years (IQR 7.4-14.5), 47% female. Median time between first and last fsOGTT=3.16 years (IQR 2.99-3.76). The rates of change for IGI and oDI pre vs post-ETI were not significantly different (Table). Conclusion: In our small sample of pwCF, we did not find significant differences in insulin secretion or oDI change before vs after ETI initiation. Disclosure M. Maher: None. T. Vigers: None. A. Moheet: None. A. Granados: None. K. Larson Ode: None. C.L. Chan: None. Funding Cystic Fibrosis Foundation (CHAN16GE0, LARSON18A0, MAHER24B0), Colorado REDCap NIH support (UL1 TR002535)