Glycemia and β-cell function before and after elexacaftor/tezacaftor/ivacaftor in youth and adults with cystic fibrosis

Christine L. Chan, Andrea Granados, Amir Moheet, Sachinkumar Singh, Timothy Vigers, Ana Maria Arbeláez, Yaling Yi, Shanming Hu, Andrew W. Norris, Katie Larson Ode

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear. Methods: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), insulin resistance (HOMA2 IR and IS(OGTT Cpep)), and β-cell function (C-peptide oral disposition index, oDIcoeo), were compared before and after ETI. Results: Participants were a median (IQR) of 20.4 (14.1, 28.6) years old, 75 % male. Follow-up occurred 10.5 (10.0, 12.3) months after ETI initiation. BMI z-score increased from 0.3 (-0.3, 0.8) to 0.8 (0.4, 1.5), p = 0.013 between visits. No significant differences were observed in glucose tolerance, glucose area under the curve, nor fsOGTT glucose concentrations before and after ETI. Median (IQR) C-peptide index increased from 5.7 (4.1, 8.3) to 8.8 (5.5, 10.8) p = 0.013 and HOMA2 IR increased (p < 0.001), while oDIcoeo was unchanged (p = 0.67). HbA1c decreased from 5.5 % (5.5, 5.8) to 5.4 % (5.2, 5.6) (p = 0.003) while CGM variables did not change. Conclusions: BMI z-score and measures of both insulin resistance and insulin secretion increased within the first year of ETI initiation. β-cell function adjusted for insulin sensitivity (oDIcoeo) did not change.

Original languageEnglish (US)
Article number100311
JournalJournal of Clinical and Translational Endocrinology
Volume30
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This work was supported by Cystic Fibrosis Foundation Grant LARSON18A0 (KLO), RC2-DK124207 (AWN), and R01-DK115791 (AWN), 5 P30 DK054759-23 (Center for Gene Therapy of Cystic Fibrosis, John Engelhardt PI, provided salary support for SS).

Publisher Copyright:
© 2022 The Authors

Keywords

  • Elexacaftor/tezacaftor/ivacaftor
  • Hemoglobin A1c
  • Insulin resistance
  • Insulin secretion
  • Oral glucose tolerance testing
  • [3–6]: Cystic fibrosis related diabetes

Fingerprint

Dive into the research topics of 'Glycemia and β-cell function before and after elexacaftor/tezacaftor/ivacaftor in youth and adults with cystic fibrosis'. Together they form a unique fingerprint.

Cite this