Mediation of the total effect of cystic fibrosis-related diabetes on mortality: A UK Cystic Fibrosis Registry cohort study

Kamaryn T Tanner ORCID logo; Rhian M Daniel ORCID logo; Diana Bilton ORCID logo; Nicholas J Simmonds; Linda D Sharples ORCID logo; Ruth H Keogh ORCID logo; (2022) Mediation of the total effect of cystic fibrosis-related diabetes on mortality: A UK Cystic Fibrosis Registry cohort study. Diabetic medicine, 39 (11). e14958. ISSN 0742-3071 DOI: 10.1111/dme.14958
Copy

AIM: To investigate whether the effect of cystic fibrosis-related diabetes (CFRD) on the composite outcome of mortality or transplant could act through lung function, pulmonary exacerbations and/or nutritional status. METHODS: A retrospective cohort of adult cystic fibrosis (CF) patients who had not been diagnosed with CFRD were identified from the UK Cystic Fibrosis Registry (n = 2750). Rate of death or transplant was compared between patients who did and did not develop CFRD (with insulin use) during follow-up using Poisson regression, separately by sex. Causal mediation methods were used to investigate whether lung function, pulmonary exacerbations and nutritional status lie on the causal pathway between insulin-treated CFRD and mortality/transplant. RESULTS: At all ages, the mortality/transplant rate was higher in both men and women diagnosed with CFRD. Pulmonary exacerbations were the strongest mediator of the effect of CFRD on mortality/transplant, with an estimated 15% [95% CI: 7%, 28%] of the effect at 2 years post-CFRD diagnosis attributed to exacerbations, growing to 24% [95% CI: 9%, 46%] at 4 years post-diagnosis. Neither lung function nor nutritional status were found to be significant mediators of this effect. Estimates were similar but with wider confidence intervals in a cohort that additionally included people with CFRD but not using insulin. CONCLUSION: There is evidence that pulmonary exacerbations mediate the effect of CFRD on mortality but, as they are estimated to mediate less than one-quarter of the total effect, the mechanism through which CFRD influences survival may involve other factors.


picture_as_pdf
Tanner_etal_2022_Mediation-of-the-total-effect.pdf
subject
Published Version
Available under Creative Commons: 4.0

View Download

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads