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

Rikke Spragge Ekblond*, Bibi Uhre Nielsen, Christine Højte, Thomas Peter Almdal, James Shaw, Tacjana Pressler, Daniel Faurholt-Jepsen, Inger Hee Mabuza Mathiesen

*Corresponding author for this work

Abstract

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.

Original languageEnglish
JournalPediatric Pulmonology
Volume58
Issue number9
Pages (from-to)2600-2609
Number of pages10
ISSN8755-6863
DOIs
Publication statusPublished - Sept 2023

Keywords

  • Adult
  • Aminophenols/therapeutic use
  • Benzodioxoles
  • C-Peptide
  • Cystic Fibrosis Transmembrane Conductance Regulator/genetics
  • Cystic Fibrosis/drug therapy
  • Glucose
  • Glycated Hemoglobin
  • Humans
  • Insulin
  • Insulin Resistance
  • Mutation
  • oral glucose tolerance test
  • CFTR modulator
  • Cystic fibrosis
  • cystic fibrosis-related diabetes
  • insulin secretion
  • glucose tolerance

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