Bio-Rad D-100의 헤모글로빈 A1c 분석능 평가 = Analytical Performance of Bio-Rad D-100 on a Hemoglobin A1c Assay

다국어 초록 (Multilingual Abstract)

Background: Hemoglobin A1c (HbA1c) is considered a marker useful for the follow-up and diagnosis of diabetes and implies the importance of reliable assay methods that are traceable to a reference method. We evaluated analytical performance of a new high-performance liquid chromatography system for the HbA1c assay: D-100 from Bio-Rad Laboratories (USA).
Methods: We evaluated precision, linearity, and carry-over of D-100, according to the Clinical and Laboratory Standards Institute’s guidelines. Comparative analysis of D-100 with Integra 800 (Roche Diagnostics, Germany) and Capillarys 3 (Sebia, France) was conducted. Additionally, we evaluated the throughput of the three instruments.
Results: Precision of low- and high-concentration controls in D-100 showed a CV of less than 1%. The linearity was excellent (R2=0.999) in the range of 3.51-18.7%, and carry-over was not observed. HbA1c results of D-100 (n=144) showed good correlation with those of Integra 800 (r=0.993) and Capillarys 3 (r=0.996). The % bias between D-100 and Integra 800 or Capillarys 3 was within the allowable range at all 3 medical decision levels (5.7%, 6.5%, and 10.0%). Elapsed time in the analysis of the first sample by D-100 was shorter than that of Integra 800 (2.4 vs. 11.1 minutes), but subsequent samples took more time (0.8 vs. 0.3 minutes per sample).
Conclusions: D-100 showed reliable analytical performance with good precision and linearity, minimal carry-over, and acceptable comparative characteristics relative to other instruments. D-100 is expected to be useful for clinical measurements of HbA1c for diabetes diagnosis and theranostics.

국문 초록 (Abstract)

배경: 헤모글로빈 A1c (HbA1c)는 당뇨의 진단과 치료, 추적 관찰에 유용한 지표로서 표준화된 검사법에 의한 정확한 검사 결과를 제공하는 것이 중요하다. 본 연구에서는 고성능 액체크로마토그래피법(HPLC)을 이용하여 HbA1c를 측정하는 장비인 D-100 (Bio-Rad Laboratories, USA)의 분석 성능을 평가하고자 하였다.
방법: Clinical and Laboratory Standards Institute (CLSI)의 지침에따라 D-100의 정밀도와 직선성, 검체 간 교차오염률을 평가하였다. 그리고 D-100과 기존 운용장비인 Integra 800 (Roche Diagnostics, Germany), Capillarys 3 (Sebia, France)와의 상관성 및 일치도를 조사하였다. 마지막으로 세 검사법의 검사 소요 시간을 비교 분석하였다.
결과: D-100을 사용한 HbA1c 측정의 검사차례 내 정밀도와 총 정밀도는 저농도와 고농도 모두에서 1% 미만의 변이계수를 보였다. 직선성은 HbA1c 3.51-18.7%에서 우수하였고 검체 간 교차오염률은 관찰되지 않았다. D-100의 Integra 800과 Capillarys 3에 대한 상관성 평가(n=144)에서 상관계수는 각각 0.993, 0.996으로 높은 상관성을 보였으며 세 가지의 임상적 의사결정 농도(5.7%, 6.5%, 10.0%) 모두에서 바이어스(%bias)는 허용범위 이내에 존재하였다. 검사 소요시간은 세 장비의 특성에 따라 차이가 있었다. D-100은 Integra 800에 비해 최초 검체를 더 빨리 처리하였으나(2.4분 vs. 11.1분) 연속 검체 처리시간은 더 길었다(0.8분 vs. 0.3분).
결론: D-100은 우수한 정밀도와 직선성 및 기존의 장비와의 비교에서 높은 상관성과 빠른 검체 처리속도를 보여주었다. 임상적으로 당뇨병의 진단과 치료, 당뇨 합병증의 예방을 위한 추적 관찰에 유용하게 사용할 수 있을 것으로 예상된다.

참고문헌 (Reference)

• 1 이혜진, "당뇨병 진단기준으로 헤모글로빈A1C의 역할" 대한내과학회 79 (79): 495-499, 2010
• 2 윤우준, "공복혈당과 당화혈색소에 의한 당뇨병 진단 비교" 대한예방의학회 43 (43): 451-454, 2010
• 3 Woodworth A, "Utilization of assay performance characteristics to estimate hemoglobin A1c result reliability" 60 : 1073-1079, 2014
• 4 Bonora E, "The pros and cons of diagnosing diabetes with A1C" 34 (34): S184-S190, 2011
• 5 Weykamp C, "The IFCC Reference Measurement System for HbA1c : a 6-year progress report" 54 : 240-248, 2008
• 6 "Standards of medical care in diabetes--2012" 35 (35): S11-S63, 2012
• 7 "Standards of medical care in diabetes--2010" 33 (33): S11-S61, 2010
• 8 Braga F, "Standardization and analytical goals for glycated hemoglobin measurement" 51 : 1719-1726, 2013
• 9 Chung S, "Six Years’ Experience of accuracy-based proficiency testing for HbA1c in Korea" 37 : 92-100, 2015
• 10 Braga F, "Revaluation of biological variation of glycated hemoglobin(HbA(1c))using an accurately designed protocol and an assay traceable to the IFCC reference system" 412 : 1412-1416, 2011
• 11 Little RR, "Performance of hemoglobin A1c assay methods: good enough?" 60 : 1031-1033, 2014
• 12 Clinical and Laboratory Standards Institute, "Method comparison and bias estimation using patient samples; approved guideline. EP9-A2" Clinical and Laboratory Standards Institute 2002
• 13 Gillett MJ, "International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes" 30 : 197-200, 2009
• 14 da Rocha Fernandes J, "IDF Diabetes Atlas estimates of 2014 global health expenditures on diabetes" 117 : 48-54, 2016
• 15 Clinical and Laboratory Standards Institute, "Harmonization of glycohemoglobin measurements; approved guideline. C44-A" Clinical and Laboratory Standards Institute 2002
• 16 Krishnamurti U, "Glycohemoglobin : a primary predictor of the development or reversal of complications of diabetes mellitus" 47 : 1157-1165, 2001
• 17 Little RR, "Glycated hemoglobin standardization--National Glycohemoglobin Standardization Program(NGSP)perspective" 41 : 1191-1198, 2003
• 18 Sacks DB, "Global harmonization of hemoglobin A1c" 51 : 681-683, 2005
• 19 Guariguata L, "Global estimates of diabetes prevalence for 2013 and projections for 2035" 103 : 137-149, 2014
• 20 Sacks DB, "Executive summary : guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus" 57 : 793-798, 2011
• 21 Clinical and Laboratory Standards Institute, "Evaluation of the linearity of quantitative measurement procedures: a statistical approach; approved guideline. EP6-A" Clinical and Laboratory Standards Institute 2003
• 22 Herpol M, "Evaluation of the Sebia Capillarys 3 Tera and the Bio-Rad D-100 systems for the measurement of hemoglobin A1c" 146 : 67-77, 2016
• 23 Clinical and Laboratory Standards Institute, "Evaluation of precision performance of quantitative measurement methods; approved guideline" Clinical and Laboratory Standards Institute 2004
• 24 Lee K, "Evaluation of analytical performance of the D-100 hemoglobin testing system for Hemoglobin A1c assay" 38 : 95-101, 2016
• 25 Fleming JK, "Evaluation of HbA1c on the Roche COBAS Integra 800 clo-sed tube system" 40 : 822-827, 2007
• 26 Maesa JM, "Evaluation of Bio-Rad D-100 HbA1c analyzer against Tosoh G8 and Menarini HA-8180V" 5 : 57-64, 2016
• 27 Gerstein HC, "Effects of intensive glucose lowering in type 2 diabetes" 358 : 2545-2559, 2008
• 28 "Diagnosis and classification of diabetes mellitus" 33 (33): S62-S69, 2010
• 29 Nathan DM, "Diabetes : advances in diagnosis and treatment" 314 : 1052-1062, 2015
• 30 Icks A, "Cost-effectiveness analysis of different screening procedures for type 2 diabetes : the KORA Survey 2000" 27 : 2120-2128, 2004
• 31 이진영, "Comparison of HbA1c Analyzers: D-10, Variant II Turbo, Cobas Integra 800, and Afinion AS100" 대한진단검사의학회 30 (30): 345-350, 2010
• 32 Rohlfing CL, "Comparing analytic performance criteria : evaluation of HbA1c certification criteria as an example" 433 : 259-263, 2014
• 33 Jaisson S, "Analytical performances of the D-100TM hemoglobin testing system(Bio-Rad)for HbA1c assay" 53 : 1473-1479, 2015