Figures
- FIGURE 1
Flow chart of participant selection. CFRD: cystic fibrosis-related diabetes; CFTR: cystic fibrosis transmembrane conductance regulator; FEV1 %: % predicted forced expiratory volume in 1 s; BMI: body mass index.
- FIGURE 2
Flow of participants in each treatment group by follow-up year, for the n=1196 individuals included in the % predicted forced expiratory volume in 1 s (FEV1 %) analysis.
- FIGURE 3
Estimated effects (and 95% confidence intervals) of insulin use for 1–5 years on % predicted forced expiratory volume in 1 s (FEV1 %) for the whole cohort (“no interaction”) and for people with high, moderate or low FEV1 % at baseline. High, moderate and low FEV1 % were defined as 100, 75 and 40, respectively. IPTW: inverse-probability-of-treatment weighting.
- FIGURE 4
Estimated effects (and 95% confidence intervals) of insulin use for 1–5 years on body mass index (BMI) z-score for the whole cohort (“no interaction”) and for people with high, moderate or low BMI z-score at baseline. High, moderate and low BMI z-score was defined as the 80th, 50th and 20th percentiles of the distribution of BMI z-scores at baseline. IPTW: inverse-probability-of-treatment weighting.
Tables
- TABLE 1
Protocol for the target trial investigating the impact of insulin use on cystic fibrosis-related diabetes (CFRD) outcomes and the corresponding emulated trial using UK Cystic Fibrosis Registry data
Protocol component Target trial Emulated trial Eligibility criteria Include: Individuals diagnosed with CFRD in the UK aged 12 years and older at time of diagnosis
Exclude: Individuals who have had an organ transplant or are taking oral corticosteroids or CFTR modulators, prior to CFRD diagnosisInclude: Individuals observed in the UK CF Registry and labelled with CFRD between 2008 and 2016, meeting criteria in the target trial and who had data for at least one visit within 2 years prior to CFRD diagnosis and at least 1 year of follow-up after diagnosis
Exclude: As in the target trial. We also exclude people with missing data on baseline confounders, including outcome at baseline, or missing data on infection or pancreatic insufficiency during the follow-up periodTreatment strategies 1) Initiate insulin at CFRD diagnosis and continue to take it throughout follow-up
2) Do not initiate insulin at CFRD diagnosis and continue not to take insulin throughout follow-up. Individuals in the no insulin group may use other non-insulin treatments for CFRDAs in the target trial Assignment procedures Participants will be randomly assigned to a treatment strategy when they are diagnosed with CFRD and will be aware of the strategy to which they have been assigned In the emulated trial individuals are not randomly assigned to the treatment strategy, which is addressed in the analysis Follow-up period 1, 2, 3, 4 and 5 years from diagnosis As in the target trial Outcome We consider two outcomes:
1) FEV1 % (obtained using GLI equations)
2) Body mass index (BMI) z-scoreAs in the target trial Causal contrasts of interest Per-protocol As in the target trial Analysis plan Mean difference in outcome between treatment groups at follow-up, adjusted for baseline level. Estimated using a linear regression model for the outcome, with treatment group and baseline measure of the outcome as explanatory variables Confounding by measured baseline and time-varying covariates is addressed using IPTW of MSMs or G-formula (see section “Statistical analysis”) CFRD: cystic fibrosis-related diabetes; CF: cystic fibrosis; CFTR: cystic fibrosis transmembrane conductance regulator; FEV1 %: % predicted forced expiratory volume in 1 s; GLI: Global Lung Function Initiative; BMI: body mass index; IPTW: inverse-probability-of-treatment weighting; MSMs: marginal structural models.
- TABLE 2
Summary of characteristics at baseline by insulin use at baseline
No insulin Insulin Subjects n 488 708 Female 237 (48.6) 364 (51.4) Age years 25.3±12.0 21.9±9.0 Genotype# High risk 395 (80.9) 618 (87.3) Low risk 33 (6.8) 14 (2.0) Not assigned 60 (12.3) 76 (10.7) FEV1 % 64.6±22.0 64.2±21.4 Change in previous 12 months¶ −1.0±10.6 −2.8±10.5 BMI z-score −0.11±1.29 −0.28±1.20 Change in previous 12 months¶ −0.04±0.50 0.00±0.60 Pseudomonas aeruginosa infection 295 (60.5) 468 (66.1) Burkholderia cenocepacia complex infection 28 (5.7) 28 (4.0) Staphylococcus aureus infection 195 (40.0) 302 (42.7) Pancreatic enzyme supplements use 418 (85.7) 637 (89.9) Maximum years of post-baseline follow-up 1 55 (11.3) 79 (11.2) 2 58 (11.9) 106 (15.0) 3 78 (16.0) 118 (16.7) 4 75 (15.4) 81 (11.4) 5 222 (45.5) 324 (45.8) Continuous variables are summarised using mean±sd and categorical variables are summarised using n (%). FEV1 %: % predicted forced expiratory volume in 1 s; BMI: body mass index. #: genotype risk as described by Mckone et al. [34]. ¶: changes in FEV1 % and BMI are the changes from previous visit (i.e. difference between measures 2 years prior to cystic fibrosis-related diabetes diagnosis and 1 year prior to CFRD diagnosis).
Supplementary Material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Supplementary material 00170-2022.SUPPLEMENT
