The utility of glucose area under the curve from the oral glucose tolerance test as a screening tool for cystic fibrosis-related diabetes

Background: Consistently abnormal glucose levels on oral glucose tolerance test (OGTT) are the most effective screening tool for cystic fibrosis-related diabetes (CFRD). However, some cystic fibrosis (CF) patients demonstrate abnormal glucose profiles not reaching levels required for CFRD diagnosis and are, therefore, left untreated. Since CFRD is associated with disease deterioration, early diagnosis and treatment are desirable. Aim: To explore the association between the area under the curve of glucose (G-AUC) obtained during a five-point 2-h standard OGTT and CF disease severity parameters. Methods: All CF patients referred for an annual routine OGTT at the Hadassah CF Center between 2002 and 2018, were included. Disease severity parameters were correlated with the G-AUC. Results: Two hundred forty-two OGTTs were performed in 81 patients (mean age 19.7 ± 9.0 years); 54% were normal, 14% showed impaired glucose tolerance (IGT), 5% had values in the indeterminate range (INDET), 11% had both IGT and INDET and 16% were diagnosed with CFRD. A gradual increase in mean G-AUC was observed among the groups. In multivariate regression models, G-AUC ≥ 295 mg h/dl was independently associated with an increased number of pulmonary exacerbations (PEx). Not all the patients having this value met the CFRD definition. Conclusion: Patients who do not fulfill the criteria for CFRD may have abnormal glucose metabolism identifiable by abnormally high G-AUC values, which may be associated with more PEx. The potential advantage of treating these patients with insulin and the subsequent reduction in PEx needs further investigation.