Background: The national programs for the harmonization of hemoglobin (Hb)A1c measurements in the US [National Glycohemoglobin Standardization Program (NGSP)], Japan [Japanese Diabetes Society (JDS)/Japanese Society of Clinical Chemistry (JSCC)], and Sweden are based on different designated comparison methods (DCMs). The future basis for international standardization will be the reference system developed by the IFCC Working Group on HbA1c Standardization. The aim of the present study was to determine the relationships between the IFCC Reference Method (RM) and the DCMs. Methods: Four method-comparison studies were performed in 2001–2003. In each study five to eight pooled blood samples were measured by 11 reference laboratories of the IFCC Network of Reference Laboratories, 9 Secondary Reference Laboratories of the NGSP, 3 reference laboratories of the JDS/JSCC program, and a Swedish reference laboratory. Regression equations were determined for the relationship between the IFCC RM and each of the DCMs. Results: Significant differences were observed between the HbA1c results of the IFCC RM and those of the DCMs. Significant differences were also demonstrated between the three DCMs. However, in all cases the relationship of the DCMs with the RM were linear. There were no statistically significant differences between the regression equations calculated for each of the four studies; therefore, the results could be combined. The relationship is described by the following regression equations: NGSP-HbA1c = 0.915(IFCC-HbA1c) + 2.15% (r2 = 0.998); JDS/JSCC-HbA1c = 0.927(IFCC-HbA1c) + 1.73% (r2 = 0.997); Swedish-HbA1c = 0.989(IFCC-HbA1c) + 0.88% (r2 = 0.996). Conclusion: There is a firm and reproducible link between the IFCC RM and DCM HbA1c values.

HbA1C is the stable glucose adduct to the N-terminal group of the beta-chain of HbA0. The measurement of HbA1c in human blood is most important for the long-term control of the glycaemic state in diabetic patients. Because there was no internationally agreed reference method the IFCC Working Group on HbA1c Standardization developed a reference method which is here described. In a first step haemoglobin is cleaved into peptides by the enzyme endoproteinase Glu-C, and in a second step the glycated and non-glycated N-terminal hexapeptides of the beta-chain obtained are separated and quantified by HPLC and electrospray ionisation mass spectrometry or in a two-dimensional approach using HPLC and capillary electrophoresis with UV-detection. Both principles give identical results. HbA1c is measured as ratio between the glycated and non-glycated hexapeptides. Calibrators consisting of mixtures of highly purified HbA1c and HbA0 are used. The analytical performance of the reference method has been evaluated by an international network of reference laboratories comprising laboratories from Europe, Japan and the USA. The intercomparison studies of the network showed excellent results with intra-laboratory CVs of 0.5 to 2% and inter-laboratory CVs of 1.4 to 2.3%. Possible interferences have been carefully investigated. Due to the higher specificity of the reference method the results are lower than those generated with most of the present commercial methods which currently are calibrated with unspecific designated comparison methods. The new reference method has been approved by the member societies of the International Federation of Clinical Chemistry and Laboratory Medicine and will be the basis for the future uniform standardization of HbA1c routine assays worldwide.

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Background: The IFCC Reference Measurement System for hemoglobin (Hb)A1c (IFCC-RM) has been developed within the framework of metrologic traceability and is embedded in a network of 14 reference laboratories. This paper describes the outcome of 12 intercomparison studies (periodic evaluations to control essential elements of the IFCC-RM). Methods: Each study included: unknown samples (to test individual network laboratories); known samples (controls); recently manufactured calibrators (to check calculated assigned value); stored calibrators (to test stability) and a calibration-set (to calibrate the IFCC-RM). The unknown samples are measured by use of the IFCC-RM and the designated comparison methods [DCMs; the National Glycohemoglobin Standardization Program (NGSP) in the US, Japanese Diabetes Society/Japanese Society for Clinical Chemistry (JDS/JSCC) in Japan, and Mono-S in Sweden] are used to investigate the stability of the Master Equation (ME), the relationship between IFCC-RM and DCMs. Results: A total of 105 IFCC-RM data sets were evaluated: 95 were approved, 5 were not, and for 5 no data were submitted. Trend analysis of the MEs, expressed as change in percentage HbA1c per year, revealed 0.000% (NGSP, not significant), −0.030%, (JDS/JSCC; significant) and −0.016% (Mono-S; not significant). Evaluation of long-term performance revealed no systematic change over time; 2 laboratories showed significant bias, 1 poor reproducibility. The mean HbA1c determined by laboratories performing mass spectrometry (MS) was the same as the mean determined by laboratories using capillary electrophoresis (CE), but the reproducibility at laboratories using CE was better. One batch of new calibrators was not approved. All stored calibrators were stable. Conclusion: A sound reference system is in place to ensure continuity and stability of the analytical anchor for HbA1c.

OBJECTIVES:To examine whether anemia is associated with a higher incidence of recurrent falls. DESIGN: Prospective cohort study. SETTING: Community-dwelling sample in the Netherlands. PARTICIPANTS: Three hundred ninety-four participants aged 65 to 88 from the Longitudinal Aging Study Amsterdam. MEASUREMENTS: Anemia was defined according to World Health Organization criteria as a hemoglobin concentration less than 12 g/dL in women and less than 13 g/dL in men. Falls were prospectively determined using fall calendars that participants filled out weekly for 3 years. Recurrent fallers were identified as those who fell at least two times within 6 months during the 3-year follow-up. RESULTS: Of the 394 persons, 11.9% (18 women and 29 men) had anemia. The incidence of recurrent falls was 38.3% of anemic persons versus 19.6% of nonanemic persons (P 5.004). After adjustment for sex, age, body mass index, and diseases, anemia was significantly associated with a 1.91 times greater risk for recurrent falls (95% confidence interval 5 1.09-3.36). Poor physical function (indicated by muscle strength, physical performance, and limitations) partly mediated the association between anemia and incidence of recurrent falls. CONCLUSION: Late-life anemia is common and associated with twice the risk of recurrent falls. Muscle weakness and poor physical performance appear to partly mediate this association.