Cystic fibrosis-related diabetes (CFRD) is the most common complication of cystic fibrosis. It is associated with significantly increased morbidity and mortality in adults and children. Adolescents with cystic fibrosis have a much higher prevalence of diabetes than any other similar age population. Glucose abnormalities that precede diabetes are even more common, especially in children younger than 10 years. The pathophysiology of glucose metabolic abnormalities is poorly understood, but insulin insufficiency is clearly the main component. Findings from animal studies have provided insight into the pathophysiology of CFRD, and imply that carbohydrate metabolic abnormalities might begin at much younger ages than was previously thought in patients with cystic fibrosis, and might be related to the basic cystic fibrosis chloride channel defect. In this Review we explore present knowledge of CFRD in children and adolescents, and new data that indicate that the pathophysiology of CFRD begins in very young patients.
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Studies of the CFTR-null ferret and the CFTR-null and ΔF508 pigs are assessing the effects of CFTR mutations on young animal models to further examine the pathophysiology of CFRD. Cell culture studies funded by the US National Institutes of Health are also underway involving isolated islets from human beings, ferrets, and pigs, including CFTR knockout, ΔF508, and wild type. These studies will help to delineate the role of CFTR in insulin secretion.