TY - JOUR

T1 - Changes in glucose tolerance in people with cystic fibrosis after initiation of first-generation CFTR modulator treatment

AU - Ekblond, Rikke Spragge

AU - Nielsen, Bibi Uhre

AU - Højte, Christine

AU - Almdal, Thomas Peter

AU - Shaw, James

AU - Pressler, Tacjana

AU - Faurholt-Jepsen, Daniel

AU - Mathiesen, Inger Hee Mabuza

N1 - © 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.

PY - 2023/6/21

Y1 - 2023/6/21

N2 - Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been shown to have a beneficial effect on pulmonary function and nutritional status in patients with cystic fibrosis (CF), but the extent to which they affect glucose tolerance is not fully understood. In the current study, we evaluated the change in glucose tolerance and insulin secretion after first-generation CFTR modulator treatment in adults with CF.Methods: We performed a longitudinal observational study with an oral glucose tolerance test performed at baseline and after three and a half years of follow-up. The test comprised glucose, C-peptide and insulin measured at fasting, 1 h, and 2 h, and HbA1c at fasting. We compared changes in parameters of glucose tolerance and insulin secretion from baseline to follow-up.Results: Among 55 participants, 37 (67%) were treated with a first-generation CFTR modulator for a median of 21 months. Glucose levels were unchanged in both the treated and untreated group. In the treated group, C-peptide levels declined, yet no significant differences in glucose, insulin, and C-peptide levels were observed between the groups. HbA1c increased in both groups, while no significant change in the insulin sensitivity indices was detected in either group. However, homeostatic model assessment for insulin resistance tended to decline in the treated group, whilst tending towards an increase in the untreated group. The difference between the groups reached statistical significance (p = 0.040).Conclusion: Treatment with first-generation CFTR modulators, mainly tezacaftor/ivacaftor, did not seem to be associated with glucose tolerance nor insulin secretion in adults with CF. However, CFTR modulators may still have a beneficial effect on insulin sensitivity.

AB - Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been shown to have a beneficial effect on pulmonary function and nutritional status in patients with cystic fibrosis (CF), but the extent to which they affect glucose tolerance is not fully understood. In the current study, we evaluated the change in glucose tolerance and insulin secretion after first-generation CFTR modulator treatment in adults with CF.Methods: We performed a longitudinal observational study with an oral glucose tolerance test performed at baseline and after three and a half years of follow-up. The test comprised glucose, C-peptide and insulin measured at fasting, 1 h, and 2 h, and HbA1c at fasting. We compared changes in parameters of glucose tolerance and insulin secretion from baseline to follow-up.Results: Among 55 participants, 37 (67%) were treated with a first-generation CFTR modulator for a median of 21 months. Glucose levels were unchanged in both the treated and untreated group. In the treated group, C-peptide levels declined, yet no significant differences in glucose, insulin, and C-peptide levels were observed between the groups. HbA1c increased in both groups, while no significant change in the insulin sensitivity indices was detected in either group. However, homeostatic model assessment for insulin resistance tended to decline in the treated group, whilst tending towards an increase in the untreated group. The difference between the groups reached statistical significance (p = 0.040).Conclusion: Treatment with first-generation CFTR modulators, mainly tezacaftor/ivacaftor, did not seem to be associated with glucose tolerance nor insulin secretion in adults with CF. However, CFTR modulators may still have a beneficial effect on insulin sensitivity.

KW - Faculty of Science

KW - CFTR modulator

KW - Cystic fibrosis

KW - Cystic fibrosis‐related diabetes

KW - Glucose tolerance

KW - Insulin secretion

KW - Oral glucose tolerance test

U2 - 10.1002/ppul.26562

DO - 10.1002/ppul.26562

M3 - Journal article

C2 - 37341613

SP - 2600

EP - 2609

JO - Pediatric pulmonology. Supplement

JF - Pediatric pulmonology. Supplement

SN - 1054-187X

ER -