Cystic fibrosis-related diabetes (CFRD) is a common complication in over 50 % of adult people with CF (PwCF).1 It has been associated with poorer clinical outcomes, including accelerated pulmonary function decline and excess morbidity.2,3 The clinical significance of early glucose abnormalities in PwCF, particularly in absence of CFRD, is being evaluated in ongoing studies.4 As controversy remains in the clinical impact of glucose tolerances abnormalities before the onset of CFRD,5,6 studies have demonstrated decline in pulmonary function and body mass index up to 5 years prior to a diagnosis of CFRD by OGTT.7,8 It suggests that abnormalities in glucose metabolism occur earlier than clinically recognized. This provides a potential opportunity for earlier intervention in order to reduce associated morbidity and mortality, and thus justifies early screening.

Several sets of guidelines propose definitions of glucose tolerance abnormalities in CF based on 2-h blood glucose levels following oral glucose tolerance testing (OGTT), starting at 10 years of age, when CFRD prevalence begins to rise.9,10 Current gold standard criteria for CFRD diagnosis are based on the OGTT and extrapolated from American Diabetes Association (ADA) type 2 diabetes guidelines. However, thresholds (fasting glucose ≥126 mg/dL and 2-h glucose ≥200 mg/dL) are intended to identify the glucose value at which the risk for microvascular complications, largely retinopathy, increases in adults with type 2 diabetes. In addition to the burden of OGTT (mild but frequent side effects, patient and clinician-time costs), it has suggested that 2-h blood glucose presents more variability in people with CF.11 Several authors reported the usefulness of determining 1-h plasma glucose levels following OGTT, enabling earlier detection of hyperglycaemia.12 One-hour hyperglycaemia in OGTT appeared to correlate more strongly with continuous glucose monitoring (CGM) data than 2-h hyperglycaemia.13

Given the limitations of current approaches to CFRD screening and diagnosis, CGM is increasingly being used, as it can detect glycaemic abnormalities earlier than other tests.14,15 Prior studies have shown the benefits of CGM in CF and report an association between CGM abnormalities and clinical deterioration. CGM can reveal hyperglycaemia that is undetectable using OGTT.16 Correlations between CGM glucose >200 mg/dL, area under the curve (AUC) >140 mg/dL, percentage of time > 140 mg/dL and lung function decline have been described,17, 18, 19 and between CGM time spent over 140 mg/dL and poor weight gain in CF.20 Although an increasing number of retrospective and cross-sectional studies are linking CGM abnormalities with clinical deterioration in CF, prospective studies are lacking in the literature.

Therefore, over a five-year prospective longitudinal multicentre study, we aimed to analyse the association between early glucose abnormalities revealed by 2-h standard OGTT and CGM on lung function decline in PwCF without known CFRD.