title: HbA1c as a screening tool for cystic fibrosis related diabetes.
abstract: OBJECTIVE
  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%.
authors: National Heart and Lung Institute, Imperial College, London, United Kingdom; Adult Cystic Fibrosis Centre, Royal Brompton Hospital, London, United Kingdom.
authors: Juliana C
authors: JC
authors: Burgess
authors: Chelsea Children's Hospital, Chelsea and Westminster NHS Healthcare Trust, Endocrinology and Diabetes, London, United Kingdom.
authors: Nicola
authors: N
authors: Bridges
authors: Medical Statistician, Respiratory Biomedical Research Unit, Royal Brompton Hospital, London, UK.
authors: Winston
authors: W
authors: Banya
authors: Adult Cystic Fibrosis Centre, Royal Brompton Hospital, London, United Kingdom.
authors: Khin M
authors: KM
authors: Gyi
authors: National Heart and Lung Institute, Imperial College, London, United Kingdom; Adult Cystic Fibrosis Centre, Royal Brompton Hospital, London, United Kingdom.
authors: Margaret E
authors: ME
authors: Hodson
authors: Adult Cystic Fibrosis Centre, Royal Brompton Hospital, London, United Kingdom.
authors: Diana
authors: D
authors: Bilton
authors: National Heart and Lung Institute, Imperial College, London, United Kingdom; Adult Cystic Fibrosis Centre, Royal Brompton Hospital, London, United Kingdom. Electronic address: n.simmonds@imperial.ac.uk.
authors: Nicholas J
authors: NJ
authors: Simmonds
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Cystic fibrosis; Cystic fibrosis related diabetes; HbA1c; Oral glucose tolerance test