title: Comparison of IFCC-calibrated HbA(1c) from laboratory and point of care testing systems.
abstract: OBJECTIVE
  WHO, IDF and ADA recommend HbA(1c) ≥6.5% (48 mmol/mol) for diagnosis of diabetes with pre-diabetes 6.0% (42 mmol/mol) [WHO] or 5.7% (39 mmol/mol) [ADA] to 6.4% (47 mmol/mol). We have compared HbA(1c) from several methods for research relating glycaemic markers.
  
  
  METHODS
  HbA1c was measured in EDTA blood from 128 patients with diabetes on IE HPLC analysers (Bio-Rad Variant II NU, Menarini HA8160 and Tosoh G8), point of care systems, POCT, (A1cNow+ disposable cartridges and DCA 2000(®)+ analyser), affinity chromatography (Primus Ultra2) and the IFCC secondary reference method (Menarini HA8160 calibrated using IFCC SRM protocol).
  
  
  RESULTS
  Median (IQ range) on IFCC SRM was 7.5% (6.8-8.4) (58(51-68) mmol/mol) HbA(1c) with minimum 5.3%(34 mmol/mol)/maximum 11.9%(107 mmol/mol). There were positive offsets between IFCC SRM and Bio-Rad Variant II NU, mean difference (1SD), +0.33%(0.17) (+3.6(1.9) mmol/mol), r(2)=0.984, p<0.001 and Tosoh G8, +0.22%(0.20) (2.4(2.2) mmol/mol), r(2)=0.976, p<0.001 with a very small negative difference -0.04%(0.11) (-0.4(1.2) mmol/mol), r(2)=0.992, p<0.001 for Menarini HA8160. POCT methods were less precise with negative offsets for DCA 2000(®)+ analyser -0.13%(0.28) (-1.4(3.1) mmol/mol), r(2)=0.955, p<0.001 and A1cNow+ cartridges -0.70%(0.67) (-7.7(7.3) mmol/mol), r(2)=0.699, p<0.001 (n=113). Positive biases for Tosoh and Bio-Rad (compared with IFCC SRM) have been eliminated by subsequent revision of calibration.
  
  
  CONCLUSIONS
  Small differences observed between IFCC-calibrated and NGSP certified methods across a wide HbA(1c) range were confirmed by quality control and external quality assurance. As these offsets affect estimates of diabetes prevalence, the analyser (and calibrator) employed should be considered when evaluating diagnostic data.
authors.affiliation: Clinical Biochemistry and Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Division of Medical Sciences, University of Birmingham, Birmingham, UK. Electronic address: susan.manley@uhb.nhs.uk.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Manley
authors.affiliation: Clinical Biochemistry and Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Hikin
authors.affiliation: Clinical Biochemistry and Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Round
authors.affiliation: Clinical Biochemistry and Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Manning
authors.affiliation: Diabetes Research Group, Swansea University, Swansea, UK.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Luzio
authors.affiliation: Diabetes Research Group, Swansea University, Swansea, UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Dunseath
authors.affiliation: Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Nightingale
authors.affiliation: Gloucester Diabetic Retinopathy Research Group, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Stratton
authors.affiliation: Clinical Biochemistry and Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Division of Medical Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Cramb
authors.affiliation: Melbourne Pathology, Melbourne, Australia.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Sikaris
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Stephen C L
authors.initials: SC
authors.lastname: Gough
authors.affiliation: Diabetes Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Webber
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002138:Calibration / Q000592:standards; D002846:Chromatography, Affinity / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D003920:Diabetes Mellitus / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019095:Point-of-Care Systems / Q000592:standards; D011786:Quality Control
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Diabetes; Diagnosis; HbA(1c) measurement; IFCC-calibrated HbA(1c); Pre-diabetes