ESPE Abstracts (2022) 95 RFC8.6

ESPE2022 Rapid Free Communications Diabetes and Insulin (6 abstracts)

Short-term effects of elexacaftor/tezacaftor/ivacaftor modulator therapy on glucose tolerance in young people with cystic fibrosis

Insa Korten 1 , Elisabeth Kieninger 1 , Linn Krueger 1 , Marina Bullo 1 , Christa E. Flück 2,3 , Philipp Latzin 1 , Carmen Casaulta 1 & Claudia Boettcher 2,3


1Division of Paediatric Respiratory Medicine and Allergology, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 2Department of Paediatric Endocrinology, Diabetology & Metabolism, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 3Department of BioMedical Research, Bern University Hospital and University of Bern, Bern, Switzerland

Background: CFRD is a unique subtype of diabetes mellitus, distinct from type 1 and type 2, harbouring β-cell dysfunction and β-cell loss and insulin resistance. Modulator therapies directly target the underlying defect of CF, modulating or correcting the function of the CFTR gene (mutation-specific). Few studies investigated the effect of modulators on CFRD and glucose metabolism. We performed an observational study on the short-term effects of the triple-modulator-therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on glucose tolerance in people with CF.

Methods: 16 adolescents with CF (homozygous or heterozygous F508-CFTR variant) underwent oral glucose tolerance tests (OGTT) before and four- six weeks after initiating ELX/TEZ/IVA therapy. A continuous glucose monitoring (CGM) system was used three days before until seven days after starting ELX/TEZ/IVA. OGTT results were categorised into normal glucose tolerance (NGT), indeterminate glucose tolerance (INDET), a combined group of impaired fasting glucose/impaired glucose tolerance (IGT) and CFRD. In terms of CGM measurements, we calculated the percentage of time of glucose levels within the following categories: Very low (≤ 2.7 mmol/L), low (≥ 2.8 and ≤ 3.3 mmol/L), normal (≥ 3.4 and ≤ 7.7 mmol/L), high (≥ 7.8 and ≤ 11.1 mmol/L), and very high (≥ 11.2 mmol/L). People with known CFRD were excluded.

Results: OGTT results were available from 15 adolescents. Before ELX/TEZ/IVA treatment, OGTTs resulted in two new diagnoses of CFRD; six participants were categorised as having IGT, two as INDET and five as NGT. OGTT categories improved after initiating ELX/TEZ/IVA (P=0.02): no participant fell into the category CFRD, two into the category IGT, four into INDET and nine into NGT. Glucose levels of OGTT improved at 60, 90 and 120 min (P< 0.05), whereas fasting glucose did not change. Eleven participants successfully performed CGM measurements. We did not find a difference in the percentage of the respective glucose level time before and after ELX/TEZ/IVA initiation. No episodes of hypoglycaemia (very low and low category) were observed after starting ELX/TEZ/IVA. Episodes of hyperglycaemia were similar before and after starting ELX/TEZ/IVA treatment (3.0% [IQR 0.6 - 4.46] vs 1.2% [IQR 0.84- 2.08].

Conclusions: Shortly after initiating ELX/TEZ/IVA therapy, glucose tolerance measured by OGTT improved in people with CF. This pilot study indicates that ELX/TEZ/IVA treatment has beneficial effects on the endocrine pancreatic function and might prevent or at least postpone future CFRD.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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