Diabetes mellitus is the most common comorbidity in cystic fibrosis (CF), occurring in a variable number of children and adolescents. Glucose metabolism derangements (GMDs) are responsible for a negative impact on the general health status of CF patients. Screening of GMDs is important since the youngest age and should be performed by means of OGTT, including its intermediate times, that could detect other non-traditional GMDs. Insulin treatment, administered before overt diabetes, could be beneficial in reducing the number of pulmonary infections, in improving both pulmonary function and nutritional status. Early screening of GMDs in pediatric age can exert an important preventing role regarding all aspects of health status of patients with CF.