Effect of CFTR modulator therapy on cystic fibrosis-related diabetes

Abstract

Background: Half of adults with cystic fibrosis (CF) develop CF-related diabetes (CFRD). CFRD contributes to worsened pulmonary function and malnutrition. We undertook this study to determine the effect of cystic fibrosis transmembrane regulator (CFTR) modulators on CRFD.

Methods: We reviewed the medical records of adults with CF who followed in the CF clinic at Oklahoma University Medical Center. We collected data for age at diagnosis of CF and CFRD, CF mutations present, first date of ivacaftor therapy either alone or in combination, insulin use, pulmonary function, body mass index data, and home glucose monitoring results. Clinical resolution of CFRD was taken as discontinuation of routine insulin and resolution of high interstitial home glucose values.

Results: We identified 69 adult CF patients, of whom 31 had CFRD. Among these 14 CFRD patients taking ivacaftor alone or in combination, four patients completely stopped using insulin. Another patient went from three times a day pre-prandial insulin to using insulin once a week. Home blood glucose and hemoglobin A1c values supported resolution of CFRD. Three patients continued to have hypoglycemia despite stopping insulin. No CFRD patient not taking CFTR modulators markedly changed the insulin regimen. Pulmonary function was preserved in those patients with resolved CFRD (FEV₁ +6.75% ±7.6), whereas it worsened in CFRD patients who either were not taking CFTR modulators (FEV₁ -2.09% ±3.9) or who had no response of CFRD status (FEV₁ -4.9% ±7.6).

Conclusions: About one-third of patients on CFTR modulator therapy had resolution or near resolution of CFRD.

Keywords: Cystic fibrosis (CF); Cystic fibrosis-related diabetes (CFRD); Ivacaftor.

Figure 1.

Distribution of relative difference in FEV₁ by Group number. Values are derived using formula: [(2018 FEV₁ value) – (2016 FEV₁ value)]/(2016 FEV₁ value). Exact Wilcoxon rank test shows significant difference (one-sided p value = 0.012) for Group 1 (+0.2086) vs Group 2 (−0.1003), and significant difference (one-sided p value = 0.0291) for Group 1 vs Group 3 (0.00793).

Figure 2.

Distribution of relative difference in BMI by Group number. Values are derived using formula: [(2018 BMI value) – (2016 BMI value)]/(2016 BMI value). Exact Wilcoxon rank test shows no significant difference for Group 1 vs Group 2 (one-sided p value is 0.1576), and no significant difference for Group 1 vs group 3 (one-sided p value is 0.2231).