Pediatric Diabetes 2008: 9(Part I): 338–344 doi: 10.1111/j.1399-5448.2008.00437.x All rights reserved # 2008 The Authors Journal compilation # 2008 Blackwell Munksgaard Pediatric Diabetes ISPAD Clinical Practice Consensus Guidelines 2008 Management of cystic fibrosis-related diabetes O’Riordan SMP, Robinson PD, Donaghue KC, Moran A. Management of cystic fibrosis-related diabetes. Pediatric Diabetes 2008: 9(Part I): 338–344. Stephen MP O’Riordan a , Paul D Robinson b , Kim C Donaghue c and Antoinette Moran d a The Developmental Endocrinology Research Group, The Institute of Child Health, University College London, London, UK; b Department of Respiratory Medicine, The Children’s Hospital at Westmead, University of Sydney, Sydney, Australia; c Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, University of Sydney, Sydney, Australia; and d Department of Pediatrics, University of Minnesota Children’s Hospital, Minneapolis, MN, USA Corresponding author: Dr Stephen MP O’Riordan MRCPI, MD The Developmental Endocrinology and Research Group The Department of Clinical and Molecular Genetics The Institute of Child Health, University College London 30 Guliford Street London WC1N 1EH Tel: 144-020-7242-9789, ext. 0732; fax: 144-020-7404-6191 e-mail: s.oriordan@ich.ucl.ac.uk Acknowledgements: Peter Hindmarsh, Mehul Dattani, Hilary Hoey, and Nicola Bridges Editors of the ISPAD Clinical Practice Consensus Guidelines 2008: Kim Donaghue, Ragnar Hanas, Georgeanna Klingensmith, and Peter Swift. Cystic fibrosis (CF) is the most common lethal genetic autosomal recessive disease in Caucasians, with a worldwide prevalence of 1 in 2500 live births. Cystic fibrosis-related diabetes (CFRD) has emerged as the most common co-morbidity in CF (1, 2). There are important differences between CFRD and both type 1 diabetes (T1D) and type 2 diabetes (T2D), which necessitate a unique approach to diagnosis and man- agement (Table 1). Definitions Modified oral glucose tolerance test (OGTT) categories have been developed by the 1998 North American CFRD Consensus Committee in reporting CFRD with and without fasting hyperglycemia [fasting plasma glucose 7.0 mmol/L (126 mg/dL) or ,7 mmol/L; and 2-h plasma glucose 11.1 mmol/L (200 mg/dL)] based on the suggestion that the prognosis may differ between these two groups in CF (2) (E). CFRD falls at one end of a spectrum of progressive glucose tolerance abnormalities. Few CF patients have completely nor- mal blood glucose levels at all times. The earliest change is variable, intermittent postprandial hyperglycemia, followed by impaired glucose tolerance (IGT), then diabetes without fasting hyperglycemia, and diabetes with fasting hyperglycemia. A diagnosis of Ônormal’ glucose tolerance on oral glucose tolerance testing does not exclude abnormal postprandial glucose levels at home (when far more than 75 g of carbohydrate may be consumed) (2) (B). Assigning a specific diagnostic category to CF pa- tients is complicated by the fact that glucose tolerance and insulin resistance are often variable in an individual subject. Factors specific to CF that cause fluctuations in glucose metabolism include: respiratory infection and inflammation, increased energy expenditure, mal- nutrition, glucagon deficiency, and gastrointestinal abnormalities (malabsorption, altered gastric emptying and intestinal motility and liver disease). Prevalence The reported prevalence of CFRD varies depending on the screening and diagnostic criteria utilized. The prevalence may be underestimated at centers where universal screening is not undertaken. While it can occur at any age, CFRD prevalence increases with age: 9% of 5–9 yr olds, 26% of 10–20 yr olds [Minnesota (3)] (Fig. 1) and 50% by 30 yr [Denmark (4)]. Repeated OGTTs have shown that glucose tolerance status can vary from year to year in CF patients (5) (B). Pathophysiology of CFRD Genetics of CFRD and relation to the CF mutation CFRD mainly occurs in people with the most severe CF mutations, all of which are associated with 338