LBODP085 Effects Of Elexacaftor-tezacaftor-ivacaftor On Glucose Tolerance And Other Metabolic Parameters In Children With Cystic Fibrosis

Cystic fibrosis related diabetes (CFRD) occurs in up to 20% of teenagers and has detrimental effects on lung function and nutritional status. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have had positive and mixed effects on glucose tolerance in children. Our study aimed to investigate the effect of elexacaftor-tezacaftor-ivacaftor (ETI) on glucose tolerance, as well as on anthropometric measures and lipids, in children. We hypothesized that glucose tolerance and BMI would improve. We completed a retrospective study of children at a Pediatric Cystic Fibrosis (CF) Center who were started on ETI after December 2019. Our inclusion criteria were children 12 years and older who were on ETI for at least one year. We did not include children on long-term corticosteroids, with type 1, type 2, or other secondary diabetes, or who were post-transplant. Blood glucose at 2 hours after an oral glucose tolerance test (2-hour BG), Hemoglobin A1c (HgbA1c), lipids, and weight and BMI z-scores were assessed after at least one year on ETI. For patients with CFRD, only HgbA1c was performed for monitoring glycemic control. These measures were compared to corresponding measures in control groups of children older than or at 12 years old, heterozygous or homozygous for F508d, who were seen at the CF Center 4 years prior, and therefore were not receiving ETI. Patients with normal and impaired glucose tolerance (NGT/IGT) were compared to controls with similar glucose tolerance and separated by age. Patients with CFRD were compared to controls with CFRD only. Average length of time on ETI was 18.7 months. CFRD was diagnosed in 8.6% of patients and impaired glucose tolerance in 13.8% of patients. Previous CFTR modulators were used in 31.6% of patients. Average 2-hour BG increased by 3.2 mg/dl (n=44, p=0.6) and average HgbA1c decreased by 0. 05% (n=53, p=0.18) after the use of ETI. Weight z-score increased by 0. 07 (n=54, p=0.38) and BMI z-score increased by 0.13 (n=58, p=0.31). Total cholesterol increased significantly by 17.6 mg/dl (n=56, p<0. 0001), but in contrast, triglycerides only increased by 4.75 mg/dl (p=0.46). Change in average 2-hour BG for children in the NGT/IGT control group (total n=30) were similar to children receiving ETI: 12-13 years: 3.6 versus 3.2 mg/dl, 13-14 years: -9. 0 versus -3.5 mg/dl, and 14-18 years: 18.5 versus 8.6 mg/dl (all p>0. 05). In children with CFRD, the control (n=7) and ETI (n=5) groups had similar changes in HgbA1c (-0.56% versus -0.5%, p=0.94). In a retrospective analysis of children, 2-hour BG and HgbA1c changed minimally after at least one year on ETI and did not differ significantly when compared to controls. Minimal changes were also seen for BMI, weight, and triglycerides after use of ETI. However, total cholesterol increased significantly with the use of ETI. Presentation: No date and time listed