Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes
Aims: Combined CFTR modulator therapies have dramatically altered pulmonary outcomes in patients with cystic fibrosis (CF). Their impact on glucose metabolism requires further investigations. This study aims to evaluate insulin requirements after initiation of combined CFTR modulator therapy in pati...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Journal of Clinical & Translational Endocrinology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221462372300008X |
| _version_ | 1827812166582927360 |
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| author | Fabian Lurquin Sophie Gohy Michel P. Hermans Vanessa Preumont |
| author_facet | Fabian Lurquin Sophie Gohy Michel P. Hermans Vanessa Preumont |
| author_sort | Fabian Lurquin |
| collection | DOAJ |
| description | Aims: Combined CFTR modulator therapies have dramatically altered pulmonary outcomes in patients with cystic fibrosis (CF). Their impact on glucose metabolism requires further investigations. This study aims to evaluate insulin requirements after initiation of combined CFTR modulator therapy in patients with CF-related diabetes (CFRD) and HOMA indices changes in CF patients without diabetes. Methods: We retrospectively analyzed: 1) the effects of tezacaftor + ivacaftor and elexacaftor + tezacaftor + ivacaftor on FEV1, weight, BMI, HbA1c, and daily insulin dose, in 17 CFRD patients and 2) the impact of tezacaftor + ivacaftor on HOMA indices in 15 CF patients without diabetes. Results: Age was 37±12y in the CFRD group (70% men), 88% of whom were homozygous for F508del mutation. Diabetes duration was 15±10y. Median duration of combined CFTR modulator therapy was 16 months (IQR: 4) Thirteen patients received tezacaftor + ivacaftor, of whom 9 were switched to elexacaftor + tezacaftor + ivacaftor. Four patients received elexacaftor + tezacaftor + ivacaftor up front. A decrease in insulin needs was noticed in 88% of patients (0.85±0.3 vs 0.71±0.3U/kg/day; p = 0001). Total daily insulin dose decreased from 50±16 to 44±20U/day (p = 0.017). BMI improved (20.9 (IQR: 1.90) vs 22.1 kg/m2 (IQR: 3.70); p = 0.014). HbA1c went from 7.3±1.1 to 7.7±1.6% (p = 0.072). Median age was 22y (IQR: 11) in the CF group without diabetes (67% men), 93% of whom were homozygous for F508del mutation. Duration of combined CFTR modulator therapy was 10±5 months. HOMA-B changes were not significant (129.2 (IQR: 84.8) vs 103.5% (IQR: 66.3) nor were HOMA-S changes (from 94±64 to 95±49%). HOMA-BxS decreased from 112±45 to 104±29% (NS). BMI rose from 21.9±3 to 23.1±3.5 kg/m2 (p = 0.047). HbA1c was unchanged (5.0±0.5%). FEV1 improved in both groups (+11% and + 7% of predicted value; p < 0.001; p = 0.013). Conclusion: Combined CFTR modulator therapies are correlated with a decrease in insulin doses and positive effects on BMI and FEV1. HOMA indices did not change on tezacaftor + ivacaftor among CF patients without diabetes. |
| first_indexed | 2024-03-11T23:14:05Z |
| format | Article |
| id | doaj.art-01c8f81f4e5540b9970499549a43428d |
| institution | Directory Open Access Journal |
| issn | 2214-6237 |
| language | English |
| last_indexed | 2024-03-11T23:14:05Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Clinical & Translational Endocrinology |
| spelling | doaj.art-01c8f81f4e5540b9970499549a43428d2023-09-21T04:36:41ZengElsevierJournal of Clinical & Translational Endocrinology2214-62372023-09-0133100320Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetesFabian Lurquin0Sophie Gohy1Michel P. Hermans2Vanessa Preumont3Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium; Corresponding author at: Avenue Hippocrate 10, Woluwe-Saint-Lambert 1200, Belgique.Department of Pneumology, CF Reference Center, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumDepartment of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumDepartment of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, BelgiumAims: Combined CFTR modulator therapies have dramatically altered pulmonary outcomes in patients with cystic fibrosis (CF). Their impact on glucose metabolism requires further investigations. This study aims to evaluate insulin requirements after initiation of combined CFTR modulator therapy in patients with CF-related diabetes (CFRD) and HOMA indices changes in CF patients without diabetes. Methods: We retrospectively analyzed: 1) the effects of tezacaftor + ivacaftor and elexacaftor + tezacaftor + ivacaftor on FEV1, weight, BMI, HbA1c, and daily insulin dose, in 17 CFRD patients and 2) the impact of tezacaftor + ivacaftor on HOMA indices in 15 CF patients without diabetes. Results: Age was 37±12y in the CFRD group (70% men), 88% of whom were homozygous for F508del mutation. Diabetes duration was 15±10y. Median duration of combined CFTR modulator therapy was 16 months (IQR: 4) Thirteen patients received tezacaftor + ivacaftor, of whom 9 were switched to elexacaftor + tezacaftor + ivacaftor. Four patients received elexacaftor + tezacaftor + ivacaftor up front. A decrease in insulin needs was noticed in 88% of patients (0.85±0.3 vs 0.71±0.3U/kg/day; p = 0001). Total daily insulin dose decreased from 50±16 to 44±20U/day (p = 0.017). BMI improved (20.9 (IQR: 1.90) vs 22.1 kg/m2 (IQR: 3.70); p = 0.014). HbA1c went from 7.3±1.1 to 7.7±1.6% (p = 0.072). Median age was 22y (IQR: 11) in the CF group without diabetes (67% men), 93% of whom were homozygous for F508del mutation. Duration of combined CFTR modulator therapy was 10±5 months. HOMA-B changes were not significant (129.2 (IQR: 84.8) vs 103.5% (IQR: 66.3) nor were HOMA-S changes (from 94±64 to 95±49%). HOMA-BxS decreased from 112±45 to 104±29% (NS). BMI rose from 21.9±3 to 23.1±3.5 kg/m2 (p = 0.047). HbA1c was unchanged (5.0±0.5%). FEV1 improved in both groups (+11% and + 7% of predicted value; p < 0.001; p = 0.013). Conclusion: Combined CFTR modulator therapies are correlated with a decrease in insulin doses and positive effects on BMI and FEV1. HOMA indices did not change on tezacaftor + ivacaftor among CF patients without diabetes.http://www.sciencedirect.com/science/article/pii/S221462372300008XCystic fibrosisCystic fibrosis-related diabetesCFTR modulatorsInsulin therapyHOMA |
| spellingShingle | Fabian Lurquin Sophie Gohy Michel P. Hermans Vanessa Preumont Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes Journal of Clinical & Translational Endocrinology Cystic fibrosis Cystic fibrosis-related diabetes CFTR modulators Insulin therapy HOMA |
| title | Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes |
| title_full | Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes |
| title_fullStr | Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes |
| title_full_unstemmed | Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes |
| title_short | Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes |
| title_sort | combined cftr modulator therapies are linked with anabolic benefits and insulin sparing in cystic fibrosis related diabetes |
| topic | Cystic fibrosis Cystic fibrosis-related diabetes CFTR modulators Insulin therapy HOMA |
| url | http://www.sciencedirect.com/science/article/pii/S221462372300008X |
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