RESUMEN
OBJECTIVE: Although insulin analogs have dramatically changed diabetes treatment, scarce evidence is available on those effects. We aimed to explore whether glycemic control had improved, the use of insulin analogs had been increased, and hypoglycemic events had decreased over time in Japanese pediatric patients with type 1 diabetes (T1D). METHODS: Glycated hemoglobin A1c (HbA1c) values, proportion of insulin regimens, incidence of severe hypoglycemic events, and pubertal increase in HbA1c were compared in three cohorts of childhood-onset Japanese T1D patients (567 subjects in the 1995 cohort, 754 subjects in the 2000 cohort, and 806 subjects in the 2008 cohort). RESULTS: Mean HbA1c values tended to decrease [78.5 mmol/mol (9.33%) in the 1995 cohort, 68.2 mmol/mol (8.39%) in the 2000 cohort, and 61.2 mmol/mol (7.75%) in the 2008 cohort; P < .0001]. The proportion of patients who received basal-bolus treatment tended to increase with statistical significance, as did the proportion on insulin analogs. The incidence of severe hypoglycemic events (events/100 patients/y) had decreased (19.1 in the 2000 cohort and 8.7 in the 2008 cohort; P = .02). The pubertal increase in HbA1c tended to decrease [males, 12.0 mmol/mol (1.10%) in 1995, 9.4 mmol/mol (0.85%) in 2008, and 9.4 mmol/mol (0.86%) in 2008; P = .55; females, 14.0 mmol/mol (1.28%) in 1995, 10.3 mmol/mol (0.94%) in 2000, and 4.2 mmol/mol (0.38%) in 2008; P = .0003]. CONCLUSIONS: Glycemic control and incidence of severe hypoglycemic events were chronologically improved, especially in female adolescents.
Asunto(s)
Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/epidemiología , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Lactante , Insulina/efectos adversos , Insulina/análogos & derivados , Japón/epidemiología , Masculino , Adulto JovenRESUMEN
BACKGROUND: Glycated albumin is an intermediate glycaemic control marker for which there are several measurement procedures with entirely different reference intervals. We have developed a reference measurement procedure for the purpose of standardizing glycated albumin measurements. METHODS: The isotope dilution liquid chromatography/tandem mass spectrometry method was developed as a reference measurement procedure for glycated albumin. The stable isotopes of lysine and fructosyl-lysine, which serve as an internal standard, were added to albumin isolated from serum, followed by hydrogenation. After hydrolysis of albumin with hot hydrochloric acid, the liberated lysine and fructosyl-lysine were measured by liquid chromatography/tandem mass spectrometry, and their concentrations were determined from each isotope ratio. The reference materials (JCCRM611) for determining of glycated albumin were prepared from pooled patient blood samples. RESULTS: The isotope dilution-tandem mass spectrometry calibration curve of fructosyl-lysine and lysine showed good linearity (r = 0.999). The inter-assay and intra-assay coefficient of variation values of glycated albumin measurement were 1.2 and 1.4%, respectively. The glycated albumin values of serum in patients with diabetes assessed through the use of this method showed a good relationship with routine measurement procedures (r = 0.997). The relationship of glycated albumin values of the reference material (JCCRM611) between these two methods was the same as the relationship with the patient serum samples. CONCLUSION: The Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry recommends the isotope dilution liquid chromatography/tandem mass spectrometry method as a reference measurement procedure, and JCCRM611 as a certified reference material for glycated albumin measurement. In addition, we recommend the traceability system for glycated albumin measurement.
Asunto(s)
Análisis Químico de la Sangre/normas , Albúmina Sérica/análisis , Sociedades Médicas , Cromatografía Liquida , Productos Finales de Glicación Avanzada , Humanos , Japón , Estándares de Referencia , Espectrometría de Masas en Tándem , Albúmina Sérica GlicadaRESUMEN
In 2010, the Japan Diabetes Society decided to introduce the National Glycohemoglobin Standardization Program (NGSP) values into clinical practice. Accordingly, NGSP Certification of Japanese manufacturers of HbA1c-related diagnostic reagents and instruments was initiated in February, 2012, through an NGSP network laboratory, the Asian Secondary Reference Laboratory (ASRL) #1. Traceability to the NGSP reference system can be endorsed by manufacturer certification, as well as by the College of American Pathologists (CAP) survey. Nevertheless, only a few manufacturers participate in the CAP survey in Japan. Thus, proficiency testing (PT) was proposed and executed by ASRL #1. Single-donor whole-blood samples were used for the PT. The participated measurement systems were NGSP certified. Twenty-two laboratories obtained certification through ASRL #1; 2 through the Secondary Reference Laboratory (SRL) #8; and 9 through the SRL #9. The combination plots of the bias data in this PT and in the NGSP certification performed in March and May in 2012 were consistent with each other: mean NGSP values at each level agreed well with the target value. In conclusion, PT using whole blood is useful in endorsing NGSP certification.
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Hemoglobina Glucada/análisis , Ensayos de Aptitud de Laboratorios/normas , Asia , Cromatografía Líquida de Alta Presión , Pruebas de Enzimas , Hemoglobina Glucada/normas , Humanos , Inmunoensayo , Japón , Control de Calidad , Estándares de Referencia , República de Corea , Sociedades CientíficasRESUMEN
The glycation gap (G-gap: difference between measured hemoglobin A1c [A1C] and the value predicted by its regression on the fructosamine level) is stable and associated with diabetic complications. Measuring A1C level in International Federation of Clinical Chemistry (IFCC) units (A1C-SI; mmol/mol) and National Glycohemoglobin Standardization Program units (A1C-NGSP; %) and using glycated albumin (GA) level instead of fructosamine level for calculating the G-gap, we investigated whether the G-gap is better represented by GA/A1C ratio if expressed in SI units (GA/A1C-SI ratio) rather than in NGSP units (GA/A1C-% ratio). We examined 749 Japanese children with type 1 diabetes using simultaneous GA and A1C measurements. Of these, 369 patients were examined more than five times to assess the consistency of the G-gap and the GA/A1C ratio within individuals. The relationship of GA/A1C-% ratio to the corresponding A1C-NGSP was stronger than that of GA/A1C-SI ratio to A1C-IFCC. At enrollment, the inverse relationship between the GA/A1C-SI ratio and G-gap was highly significant (R(2) = 0.95) compared with that between the GA/A1C-% ratio and G-gap (R(2) = 0.69). A highly significant inverse relationship was also observed between the mean GA/A1C-SI ratio and the mean G-gaps obtained individually over time (R(2) = 0.95) compared with that using the corresponding A1C-NGSP (R(2) = 0.67). We conclude that the G-gap is better represented by the GA/A1C-SI ratio. We propose the use of mean GA/A1C-SI ratios easily obtained individually over time as reference values in Japanese children with type 1 diabetes (6.75 ± 0.60 [means ± SD]).
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Fructosamina/sangre , Hemoglobina Glucada/análisis , Hiperglucemia/prevención & control , Albúmina Sérica/análisis , Adolescente , Algoritmos , Niño , Estudios de Cohortes , Terapia Combinada , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Dieta para Diabéticos , Femenino , Productos Finales de Glicación Avanzada , Glicosilación/efectos de los fármacos , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Sistema Internacional de Unidades , Japón , Masculino , Albúmina Sérica Humana , Albúmina Sérica GlicadaRESUMEN
The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have recently decided to use both units in the hemoglobin A1c (HbA1c) measurement based on the NGSP (previously called the National Glycohemoglobin Standardization Program) and the IFCC (International Federation of Clinical Chemistry) in articles and scientific meetings, whereas each country or region may use either NGSP units (conventional %) or IFCC units (SI; mmol/mol) in common practice. This is expressed as "a new twist on the path to harmony" in the measurement of HbA1c. Accordingly, the Japan Diabetes Society has used only NGSP units as of April 1, 2013, whereas the previous JDS units will be used for the high reproducibility of the JDS Standardization System but not in the clinical setting. JDS units are converted to NGSP units using JDS lots in Japan. Unfortunately however, there are significant differences between NGSP values obtained by the previously reported IFCC-JDS equations and those currently available in Japan. Therefore, this paper argues that IFCC units as the only valid anchor for scientific standardization should seek robust master equations for NGSP and JDS units. Furthermore, the biological variability of HbAlc, such as the Hemoglobin Glycation Index and the Glycation Gap, may be accurately evaluated by IFCC units because the values do not include additional factors such as non-glycated Hb in JDS and NGSP units.
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Biomarcadores/sangre , Diabetes Mellitus/sangre , Hemoglobina Glucada/normas , Hiperglucemia/diagnóstico , Diabetes Mellitus/diagnóstico , Hemoglobina Glucada/análisis , Humanos , JapónRESUMEN
Effective and efficient planning and development of residential environments require clarifying the nature of residential preferences. In reality, residential preferences are heterogeneous, so the standard econometric models that assume only one type of preference are not optimal. In this study, conjoint choice experiment methods are employed with a mixed logit approach. The findings reveal significant heterogeneity with regard to some residential attributes. The determinants of preference heterogeneity were also investigated by conducting regression analyses on the attributes that were valued heterogeneously. Overall, the relationships observed between the explanatory variables and the heterogeneity in the valuations were understandable. However, coefficient of determination values for each model were low, indicating that the bulk of preference heterogeneity results from unobservable factors.
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Vivienda , Características de la Residencia , Factores Socioeconómicos , Población Urbana , Historia del Siglo XX , Historia del Siglo XXI , Vivienda/economía , Vivienda/historia , Dinámica Poblacional/historia , Características de la Residencia/historia , Factores Socioeconómicos/historia , Salud Urbana/historia , Población Urbana/historiaRESUMEN
BACKGROUND: The American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD)/International Diabetes Federation (IDF)/IFCC Consensus Statement on the worldwide standardization of HbA(1c) states that "... [HbA(1c)] results are to be reported world-wide in IFCC units ... and derived NGSP units ... , using the IFCC-NGSP master equation." METHODS: We describe statistical methods to evaluate and monitor the relationships as expressed in master equations (MEs) between the IFCC Reference Measurement procedure (IFCC-RM) and designated comparison methods (DCMs) [US National Glycohemoglobin Standardization Program (NGSP), Japanese Diabetes Society/Japanese Society for Clinical Chemistry (JDS/JSCC), and Mono-S in Sweden]. We applied these statistics, including uncertainty calculations, to 12 studies in which networks of reference laboratories participated, operating the IFCC-RM and DCMs. RESULTS: For NGSP and Mono-S, slope, intercept, and derived percentage HbA(1c) at the therapeutic target show compliance with the respective MEs in all 12 studies. For JDS/JSCC, a slight deviation is seen in slope and derived percentage HbA(1c) in 2 of the 12 studies. Using the MEs, the uncertainty in an assigned value increases from 0.42 mmol/mol HbA(1c) (IFCC-RM) to 0.47 (NGSP), 0.49 (JDS/JSCC), and 0.51 (Mono-S). CONCLUSIONS: We describe sound statistical methods for the investigation of relations between networks of reference laboratories. Application of these statistical methods to the relationship between the IFCC-RM and DCMs in the US, Japan, and Sweden shows that they are suitable for the purpose, and the results support the applicability of the ADA/EASD/IDF/IFCC Consensus Statement on HbA1c measurement.
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Pruebas de Química Clínica/estadística & datos numéricos , Interpretación Estadística de Datos , Diabetes Mellitus/sangre , Hemoglobina Glucada/análisis , Pruebas de Química Clínica/métodos , Pruebas de Química Clínica/normas , Humanos , Japón , Programas Nacionales de Salud , Guías de Práctica Clínica como Asunto , Estándares de Referencia , Suecia , Incertidumbre , Estados UnidosRESUMEN
BACKGROUND: The IFCC Reference Measurement System for hemoglobin (Hb)A(1c) (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 HbA(1c) 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 HbA(1c) 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 HbA(1c).
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Pruebas de Química Clínica/normas , Hemoglobina Glucada/normas , Sesgo , Calibración , Cromatografía Líquida de Alta Presión , Electroforesis Capilar , Hemoglobina Glucada/análisis , Humanos , Modelos Lineales , Espectrometría de Masas , Control de Calidad , Estándares de Referencia , Reproducibilidad de los Resultados , IncertidumbreRESUMEN
The measurement of glycated hemoglobin is central in the monitoring of glycemic control in patients with diabetes. There are at least 30 different laboratory assays commercially available to measure the proportion of HbA1c in blood. In 1995 the IFCC established a Working Group (IFCC WG-HbA1c) to achieve international standardization of HbA1c measurement. The main achievements can be summarized as follows: a) a reference measurement procedure has been established with purified primary calibrators; b) a network of reference laboratories has been developed worldwide; and c) work has begun on implementation of traceability to the IFCC reference system. The IFCC WG-HbA1c recognizes the recommendation of the IFCC-IUPAC Committee on Nomenclature, Properties and Units that the analyte measured by the IFCC reference measurement procedure has been defined as betaN1-deoxyfructosyl-hemoglobin and that the recommended measurement units are mmol/mol. The IFCC WG-HbA1c recommends maintaining the use of the name HbA1c in clinical practice.
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Hemoglobina Glucada/análisis , Hemoglobina Glucada/normas , Humanos , Guías de Práctica Clínica como Asunto , Estándares de ReferenciaRESUMEN
BACKGROUND: The Committee on Standardization of Laboratory Testing Related to Diabetes Mellitus of the Japan Diabetes Society (JDS) previously recommended use of the primary calibrator (JDS Lot 1) prepared by the former Committee for Standardization of Glycohemoglobin for standardizing the measurement of haemoglobin A1c (HbA1c). Owing to the depletion of vials of Lot 1 in March 2001, the present committee certified a new reference material, Lot 2, now distributed by the Health Care Technology Foundation (HECTEF). The standardization programme for HbA1c measurement in Japan is currently based on Lot 2, which has values assigned from within Lot 1; the Lot 1 values were consensus values based on assays by laboratories in the Japanese national quality control programme. In this study, for the purpose of international comparison and standardization, Lot 2 was assayed by the JDS reference laboratories, the National Glycoprotein Standardization Program (NGSP) in the USA, and by reference laboratories approved by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). METHOD: The HbA1c values of JDS Lot 2 were transferred from those assigned to Lot 1 using KO500, a high-resolution HPLC method, at three laboratories approved by the JDS committee. Subsequently, vials of JDS Lot 2 were shipped to and assayed by the NGSP in the USA and 10 IFCC reference laboratories. RESULT: The JDS-assigned HbA1c values (from Lot 1) are 4.04 for Level 1, 5.38 for Level 2, 7.32 for Level 3, 9.88 for Level 4, and 12.63 for Level 5, all expressed as a percentage of total haemoglobin. The values obtained by NGSP and the IFCC laboratories gave the following formulas: NGSP value(%)=JDS value(%)+0.3%; IFCC value(%)=1.068xJDS value(%)-1.741%. CONCLUSION: Although the values obtained by the IFCC laboratories are significantly lower than the values assigned to Lot 2 by the JDS, the relationship is linear. In addition, standardization of HbA1c based on JDS Lot 2 is currently at a satisfactory level in Japan. As a result, the reassignment of values for Lot 2 to agree with the IFCC values should be relatively easy and will be done after all relevant parties agree to the change.
Asunto(s)
Análisis Químico de la Sangre/normas , Diabetes Mellitus/diagnóstico , Hemoglobina Glucada/análisis , Laboratorios/normas , Análisis Químico de la Sangre/métodos , Calibración , Hemoglobina Glucada/normas , Humanos , Cooperación Internacional , Japón , Control de Calidad , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estados UnidosRESUMEN
BACKGROUND: In 2001, the Committee on Standardization of Laboratory Testing Related to Diabetes Mellitus of the Japan Diabetes Society (JDS) prepared and certified a new reference material for haemoglobin A1c (HbA1c), Lot 2. The standardization programme for HbA1c measurement in Japan is currently based on Lot 2, although some laboratories still use the previous material (Lot 1). The values assigned to Lot 2 were based on the consensus values for Lot 1 and should give the same results. Therefore, there should be no difference in the measured values no matter which calibrators are used. The Committee conducted a domestic survey in order to confirm this relationship. METHOD: In November 2002, four samples for HbA1c assay were sent to 795 laboratories as part of a national survey in Japan. Assays were performed using the laboratories' routine clinical methods. The coefficients of variation (CVs) of the reported values from all laboratories for the samples were calculated in order to determine the current level of standardization in Japan. RESULTS: The overall CVs in the measured values for the four samples ranged from 2.7% to 4.0%. Values from laboratories using calibrators based on Lots 1 and 2 were similar. CONCLUSION: The present state of standardization for the routine measurement of HbA1c in Japan, as indicated by the 2002 survey, is excellent. This should aid in the eventual conversion of Lot 2 to IFCC-based values from the results of the 2002 national HbA1c survey.
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Análisis Químico de la Sangre/normas , Diabetes Mellitus/diagnóstico , Hemoglobina Glucada/análisis , Laboratorios/normas , Análisis Químico de la Sangre/métodos , Calibración , Cromatografía Líquida de Alta Presión , Hemoglobina Glucada/normas , Humanos , Inmunoensayo , Japón , Control de Calidad , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The national programs for the harmonization of hemoglobin (Hb)A(1c) 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 HbA(1c) 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 HbA(1c) 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-HbA(1c) = 0.915(IFCC-HbA(1c)) + 2.15% (r(2) = 0.998); JDS/JSCC-HbA(1c) = 0.927(IFCC-HbA(1c)) + 1.73% (r(2) = 0.997); Swedish-HbA(1c) = 0.989(IFCC-HbA(1c)) + 0.88% (r(2) = 0.996). CONCLUSION: There is a firm and reproducible link between the IFCC RM and DCM HbA(1c) values.
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Hemoglobina Glucada/análisis , Análisis Químico de la Sangre/métodos , Análisis Químico de la Sangre/normas , Calibración , Hemoglobina Glucada/normas , Humanos , Japón , Programas Nacionales de Salud , Estándares de Referencia , Suecia , Estados UnidosRESUMEN
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.