The Journal of clinical endocrinology and metabolism · 2025
Glycemia and Insulin Secretion in Cystic Fibrosis 2 Years After Elexacaftor/Tezacaftor/Ivacaftor: PROMISE-ENDO.
СтатьяМногоцентровое исследованиеНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Chan Christine L, Shirley Bezerra Meghan, Stefanovski Darko, Gallop Robert J, Walega Rachel, Donaldson Scott H, Frederick Carla A, Freedman Steven D, Gelfond Daniel, Hoffman Lucas R, Narkewicz Michael R, Rowe Steven M, Sagel Scott D, Schwarzenberg Sarah Jane, Solomon George M, Stalvey Michael S, Kelly Andrea
Аннотация
BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) is a highly effective therapy that improves lung disease in people with cystic fibrosis (pwCF), but its effect on glucose tolerance and insulin secretion is unclear.
METHODS: PROMISE is a multicenter prospective, observational study of ETI in pwCF ≥12 years and at least one F508del allele. The PROMISE Endocrine substudy (PROMISE-ENDO) enrolled participants at 10 CF Centers where hemoglobin A1c (HbA1c) was collected and 3-hour oral glucose tolerance tests (OGTT) conducted to examine glucose tolerance, glucose excursions, and insulin secretory rates (deconvolution of C-peptide) and sensitivity (oral minimal model) prior to ETI and 12 to 18 months and 24-30 months following ETI initiation. Longitudinal mixed effects models were used to test within-subject ETI effects.
RESULTS: At baseline, 79 participants completed OGTTs (39 [49%] male, median [IQR] age 19.6 [14.7, 27.3] years, BMI z-score 0.12 [-0.51, 0.65]). At 12-18 months n = 68 and at 24-30 months n = 58 completed OGTTs. At 24-30 months, fasting glucose (mg/dL) decreased (94 [92, 96] to 90 [88, 93], P = .02) in the subset not on insulin therapy (n = 61), but no differences in 1-hour or 2-hour glucose were found. HbA1c decreased from 5.8% (5.6%, 5.9%) to 5.5% (5.4%, 5.6%), P < .001 by 24-30 months. Although insulin sensitivity (mU/L-1 min-1) decreased (8.4 [7.2, 9.5] vs 6.8 [5.8, 7.9], P = .03), no changes in oral disposition index were found, P = .14.
CONCLUSION: After 2 years of ETI, fasting glucose and HbA1c showed modest decreases. Glucose tolerance varied, and overall measures of insulin secretion did not deteriorate.
METHODS: PROMISE is a multicenter prospective, observational study of ETI in pwCF ≥12 years and at least one F508del allele. The PROMISE Endocrine substudy (PROMISE-ENDO) enrolled participants at 10 CF Centers where hemoglobin A1c (HbA1c) was collected and 3-hour oral glucose tolerance tests (OGTT) conducted to examine glucose tolerance, glucose excursions, and insulin secretory rates (deconvolution of C-peptide) and sensitivity (oral minimal model) prior to ETI and 12 to 18 months and 24-30 months following ETI initiation. Longitudinal mixed effects models were used to test within-subject ETI effects.
RESULTS: At baseline, 79 participants completed OGTTs (39 [49%] male, median [IQR] age 19.6 [14.7, 27.3] years, BMI z-score 0.12 [-0.51, 0.65]). At 12-18 months n = 68 and at 24-30 months n = 58 completed OGTTs. At 24-30 months, fasting glucose (mg/dL) decreased (94 [92, 96] to 90 [88, 93], P = .02) in the subset not on insulin therapy (n = 61), but no differences in 1-hour or 2-hour glucose were found. HbA1c decreased from 5.8% (5.6%, 5.9%) to 5.5% (5.4%, 5.6%), P < .001 by 24-30 months. Although insulin sensitivity (mU/L-1 min-1) decreased (8.4 [7.2, 9.5] vs 6.8 [5.8, 7.9], P = .03), no changes in oral disposition index were found, P = .14.
CONCLUSION: After 2 years of ETI, fasting glucose and HbA1c showed modest decreases. Glucose tolerance varied, and overall measures of insulin secretion did not deteriorate.