1. Mediation of the total effect of cystic fibrosis-related diabetes on mortality: A UK Cystic Fibrosis Registry cohort study.
- Author
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Tanner KT, Daniel RM, Bilton D, Simmonds NJ, Sharples LD, and Keogh RH
- Subjects
- Adult, Cohort Studies, Female, Humans, Insulin therapeutic use, Male, Registries, Retrospective Studies, United Kingdom epidemiology, Cystic Fibrosis complications, Cystic Fibrosis epidemiology, Diabetes Mellitus diagnosis
- Abstract
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., (© 2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)
- Published
- 2022
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