SUN-LB026 Do CFTR Modulators Treat Cystic Fibrosis-Related Diabetes?

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are a recent advancement in the treatment of cystic fibrosis and were initially approved for their beneficial effect on lung function. There have also been few reports of their positive role in glycemic control in patients with impaired glucose tolerance and diabetes related to cystic fibrosis. Clinical Case: Ms. A is a 27yr old female who presented to our Endocrinology Clinic for cystic fibrosis-related diabetes (CFRD). She was diagnosed with diabetes in 2015.  By August 2017 her diabetes had deteriorated and she presented to the hospital with severe hyperglycemia. She had blood glucose levels over 400 mg/dL and HbA1c of 10.8% without diabetic ketoacidosis. Physical exam at that time was unremarkable. Her BMI was 21.5 kg/m(2). She then started a multiple daily injection program that included Glargine and prandial Aspart insulins. Four months later her hemoglobin A1c improved to 7.9%.   Past medical history was significant for cystic fibrosis with homozygous F508 deletion. Her cystic fibrosis had been complicated by bronchiectasis, recurrent sinusitis, pneumonia, pancreatic insufficiency and staphylococcus aureus bacteremia with sepsis. Earlier in 2018, the patient was started on treatment with Orkambi (lumacaftor/ivacaftor) and then Symdeko (tezacaftor/ivacaftor). Interestingly, subsequently Ms. A noticed an improvement of her blood glucose levels and also started having episodes of hypoglycemia. After about 10 months of use of CFTR modulators, she stopped using Glargine as well as prandial Aspart insulins and just required a couple of units of Aspart occasionally when her blood glucose levels were above target. That happened sporadically.   On her last follow up in Dec 2018, Ms. A was feeling well and denied symptoms of hyperglycemia. Her HbA1c at that time was 7.0%, despite the fact that she was not taking long-acting insulin or scheduled prandial insulin for a couple months. Conclusion: CFRD is a distinct form of diabetes mellitus sharing features of both type 1 and type 2 diabetes. In the recent years, CFTR modulators got approved for the treatment of CF showing improvement in lung function. There is limited evidence that suggests that treatment with CFTR modulators may have a beneficial effect on glycemic control in patients with CFRD with one case report showing resolution of CFRD(1). Our case supports this hypothesis. The long-term effect of these medications on progression of CFRD and associated complications is still unknown. Further studies are needed to clarify these questions. References: 1. Standards S, Organisation M. References 1. 2014;28(2013):438-453. doi:10.1016/j.pedn.2008. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.