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Background: Insulin secretion and glucose tolerance is annually assessed in patients with cystic fibrosis (PwCF) through oral glucose tolerance tests (OGTTs) as a screening measure for cystic fibrosis-related diabetes. We aimed to describe the distribution and provide reference quartiles of OGTT-related variables in the Italian cystic fibrosis population. Methods: Cross-sectional study of PwCF receiving care in three Italian cystic fibrosis centers of excellence, from 2016 to 2020. We performed a modified 2-h OGTT protocol (1.75 g/kg, maximum 75 g), sampling at baseline and at 30-min intervals, analyzing plasma glucose, serum insulin, and C-peptide. The modified OGTT allowed for the modeling of β cell function. For all variables, multivariable quantile regression was performed to estimate the median, the 25th, and 75th percentiles, with age, sex, and pancreatic insufficiency as predictors. Results: We have quantified the deterioration of glucose tolerance and insulin secretion with age according to sex and pancreatic insufficiency, highlighting a deviation from linearity both for patients <10 years and >35 years of age. Conclusions: References of OGTT variables for PwCF provide a necessary tool to not only identify patients at risk for CFRD or other cystic fibrosis-related complications, but also to evaluate the effects of promising pharmacological therapies. [ABSTRACT FROM AUTHOR]