HbA1c as a screening tool for cystic fibrosis related diabetes

Aims: Early diagnosis of cystic fibrosis (CF) related diabetes (CFRD) is important to improve outcomes. International guidelines recommend an oral glucose tolerance test (OGTT) for all CF patients aged 10 years this approach is controversial. The aim of this study was to develop an effective screening tool and reduce the need for a universal OGTT. Methods: Adult CF patients (without CFRD) attending an annual review assessment were recruited prospectively (March 2009 July 2012) into two sequential studies a primary investigative study followed by validation study. All patients underwent an OGTT and were simultaneously screened by predetermined biochemical/clinical criteria to identify their risk of CFRD. A sensitivity/specificity analysis was performed using the World Health Organisation diabetes criteria as gold standard; modifications were made to improve the screening tool's accuracy and determine the optimal screening thresholds. This was tested in the validation study. Results: 429 patients (primary, n = 94; validation, n = 335: mean age = 31.7 +/- 10.4(SD), 43% female, 77% on pancreatic supplements). Primary study: in predicting a positive OGTT, the test sensitivity was 66.7% and specificity 60%. HbA1c was carried over to the validation study as it was the most discriminative (optimal threshold >= 5.8% (40 mmol/mol); receiver operating curve, ROC, score 0.60). Validation study: the number of patients with a normal, impaired and diabetic OGTT was 268(80%), 51(15.2%) and 16(4.8%), respectively. HbA1c provided a test sensitivity, specificity and ROC score of 93.8%, 53.0% and 0.73, respectively. Conclusions: The use of HbA1c >= 5.8%(40 mmol/mol) is an effective tool for CFRD screening and reduced the need for an OGTT by 50.7%. (C) 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.