BACKGROUND: Cystic fibrosis related diabetes (CFRD) is associated with increased morbidity in CF. Variability in physiological systems is associated with dysfunctional homeostasis. We examined whether fluctuation in glucose is a marker of CFRD or "pre-diabetes". METHODS: Using a machine learning approach, we compared glucose IQR to current diagnostic criteria in a review of continuous glucose monitoring data. RESULTS: Analysis was performed on 248 studies from 142 children. Calculated IQR (cIQR) was increased between children with CFRD, normal glucose homeostasis and indeterminate status (p<0.0001) and impaired glucose tolerance (p<0.05, Kruskal-Wallis test). In subjects who developed CFRD (n=20), cIQR increased between baseline and diagnosis (1.4mmol/L versus 2.4mmol/L, p<0.0001, Wilcoxon test). Area under the curve for CFRD on the basis of cIQR was 0.865 (p<0.0001). Neither episodes of hypoglycaemia nor cIQR at baseline predicted CFRD. CONCLUSIONS: Glucose fluctuation on CGMS can be quantified by calculating the IQR. This information may improve early recognition of abnormal glucose homeostasis.