P-124: Atypical onset of cystic fibrosis related diabetes (CFRD): a case report
J Groto Rico, A Vervloet da Luz, G Adami, R Biasi, L Cudizio, L E CalliariAbstract
Introduction
Cystic Fibrosis (CF) is an autosomal recessive, multisystem disease, and Cystic Fibrosis-Related Diabetes (CFRD) is the most common extrapulmonary comorbidity. Mutations in the CFTR gene, which encodes a chloride/bicarbonate channel on epithelial cell surfaces, lead to thick, viscous secretions in multiple organs, including the pancreas. This results in inflammation, fibrosis, and progressive destruction of beta cells, culminating in insulin insufficiency. Insulin resistance may occur in more severe, advanced stages, particularly during acute exacerbations or glucocorticoid use. The diagnosis of CFRD follows the same ADA guidelines used for Type 1 and Type 2 Diabetes Mellitus. Normal fasting glucose and glycated hemoglobin do not exclude the diagnosis, making the Oral Glucose Tolerance Test (OGTT) essential. Screening should begin at age 10 and be performed annually due to the disease’s insidious progression.
Objectives
To emphasize that, although uncommon, CFRD can initially present with Diabetic Ketoacidosis (DKA), even in patients who undergo early and regular screening.
Methods
A 14y11m-old male patient with CF (p.Phe508del / intronic variant 1bp del exon), receiving Elexacaftor, Tezacaftor, and Ivacaftor since 13 years old, had shown glucose intolerance at the age of 12 based on OGTT. He remained under regular follow-up, without the need for pharmacological intervention, until the age of 14, when he developed DKA (pH 7.29, HCO3 20.2 mEq/L, glucose 500 mg/dL), requiring full-dose insulin therapy.
Results
In CF, unlike Type 1 Diabetes, the progression of insulin insufficiency is typically gradual and insidious, making DKA in CFRD uncommon. However, rapid progression can occur in some cases.
Conclusions
This finding indicates that although annual screening is essential, it does not exclude the possibility of accelerated CFRD development, reinforcing the need for individualized and continuous follow-up.