Introduction: CFTR-modulating therapy aims to restore CFTR function. It improves lung function and quality of life in CF patients however, its effects on glucose metabolism are not yet well defined.
Methodology: Retrospective and longitudinal study.
Inclusion criteria: patients with CF genetic diagnosis ≥10 years old on modulator therapy (ivacaftor + lumacaftor or ivacaftor + tezacaftor or triple therapy: elexacaftor + tezacaftor + ivacaftor) and who had OGTT ± Continuous-glucose-monitoring (CGM) performed before and after therapy onset. Tests were performed without underlying disease exacerbations or corticosteroid at the time of test or 4 weeks prior. OGTT classifies patients into normal tolerance (NGT), impaired tolerance (AGT) or diabetes (CFRD). CGM (IproTM2-Medtronic) performed for 6 days with regular exercise and diet; patients were classified as NGT: <4.5% of monitoring time >140mg/dl, AGT: ≥4.5% of monitoring time >140mg/dl or one glucose peak ≥200mg/dl and CFRD: ≥2glucose peaks ≥200mg/dl on different days.
|Patients and glucose metabolism|
|Nº||Therapy||F/M||Age (years)||Pre-therapy||Time to control study (months)||Control|
|A:lumacaftor and ivacaftor. B: tezacafor and ivacaftor. C: ivacaftor, tezacaftor and elexacaftor|
HbA1c was <6% before and at therapy control, except for patient Nº6 who started with HbA1c7.9%. Five patients (62.5%) were homozygous and 3 heterozygous for F508del mutation. Patients with pre-therapy glucose abnormalities improved and one patient without glucose abnormalities worsened. Patient nº8 required nasogastric tube feeding, insulin (CFRD) and was a lung transplant candidate before beginning triple therapy; nowadays he doesn`t need nasogastric tube feeding, stopped insulin after 16 months on therapy and he is no longer a transplant candidate. Patient nº6 had 11 peaks of postprandial glucose >200mg/dl on control CGM while OGTT showed normal glucose values (maximum 138mg/dl).
Conclusions: • CFTR-modulating therapy appears to improve glucose metabolism in patients who had glucose abnormalities.
• The effects of CFTR-modulating therapy on glucose metabolism seem to take longer than the rapid improvement observed in lung function and nutritional status.
• CGM is more sensible than OGTT to changes of glucose metabolism in CF patients.
15 Sep 2022 - 17 Sep 2022