Effects of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Modulating Therapy on Glucose Metabolism in Cystic Fibrosis Patients

Pamela Yesquen; Ariadna Campos; Eduard Mogas; Diego Yeste; Silvia Gartner; María Clemente

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.

Results:


Patients and glucose metabolism
Nº	Therapy	F/M	Age (years)	Pre-therapy		Time to control study (months)	Control
				OGTT	CGM		OGTT	CGM
1.	A	F	10,25	AGT (INDET)	--	17	NGT	--
2.	B	M	14,58	NGT	AGT	13	NGT	NTG
3.		M	15,50	NGT	NGT	7	NGT	--
4.		M	15,60	NGT	NGT	17	NGT	NTG
5.		M	17,25	NGT	NGT	13	NGT	--
6.	F	17,33	NGT	NGT	18	NGT	CFRD
7.	F	20,50	AGT	AGT	19	NGT	NGT
8.	C	M	17,50	CFRD	--	21	AGT	--
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.

ESPE Abstracts

P1-233