Background: Cystic fibrosis (CF) is an inherited disease that leads to damage to lungs, pancreas and other organs. Most people with CF die prematurely from lung disease, but survival has improved markedly over the decades and it is estimated that children born with CF now will live to an average age of 50 years. CF-related diabetes (CFRD) is due to damage to the pancreas, which, over time, loses its capacity to produce sufficient insulin. CFRD is becoming more common owing to the improved survival of people with CF. Objectives: The initial aim was to review the methods for screening for CFRD, which can be symptomless but still be causing harm. As the aim of screening and early detection is to allow earlier treatment, a second aim was to assess the effectiveness of treatments. However, during the review it became clear that there were problems with how CFRD is defined, uncertainty about when hyperglycaemia should be treated. Data sources: Details of relevant studies were obtained from the usual bibliometric databases - MEDLINE (1950-2008), EMBASE (1980-2008), The Cochrane Library (all sections), Web of Science (1970-2008). Websites of relevant bodies were searched for guidelines and reports. Conference abstracts were searched. Expert co-authors identified key papers. Review methods: Systematic reviews of treatments and screening tests. Screening studies were data extracted if they provided sufficient data to construct 2 x 2 tables. Other screening studies were described in narrative manner. The background to CF and CFRD were described in a narrative manner, as was Chapter 2 on problems with defining CFRD. A model was constructed for cost-effectiveness analysis, but was not used because of lack of data. Results: Diabetes is usually defined based on the level of blood glucose (BG) at which the risk of retinopathy occurs. For CFRD, it would be better to define it on the level at which the risk of lung disease (pulmonopathy) rises. There seems little place for treatments other than insulin, but the best insulin regimen remains to be confirmed. The best screening test may be by continuous glucose monitoring systems but further evidence is required. Screening may need to detect BG levels of >8 mmol/l because that may be the level above which pulmonopathy starts in people with CF. Limitations: The evidence base for treatment is disappointing with few large randomised controlled trials. The key question is when treatment should start, perhaps at the postprandial hyperglycaemia stage. Research is needed. Until that is done, we cannot be sure what we are screening for, and, therefore, which screening strategy should be used. Conclusions: The definition of CFRD should probably be based on pulmonopathy risk, rather than using the classical definition of diabetes. That implies that we should be screening for a wider range of hyperglycaemia than in other forms of diabetes, perhaps to detect BG excursions of >8 mmol/l. Insulin treatment may need to start at lower levels than formerly accepted.
