HbA1c Assay Research Articles

Hb Tacoma by seven HbA1c methods – one with significant interference

Hemoglobin Tacoma is known to potentially interfere HbA1c assays. The variant is common in Finland with prevalence of up to 2% regionally and cases are also reported in areas that have attracted Finnish immigrants, especially in Sweden and North America. Here, we investigated the effect of Hb Tacoma on seven HbA1c methods. 20 non-variant and 20 Hb Tacoma samples were measured with Tina-quant Gen. 3 (immunoassay, considered as reference) and the following point of care instruments: Afinion 2, HbA1c 501 (both utilizing boronate affinity), QuikRead go, cobas b 101, DCA Atellica, and Standard F (all immunoassays). Repeatability was also assessed by measuring both non-variant and Hb Tacoma samples five times each at two different levels. For non-variant samples, the mean relative bias with all methods was < ±4%, whereas for Hb Tacoma samples Standard F had 38% mean relative bias. In absolute bias, the difference was 17 mmol/mol on average and constant through the measured range. For other methods the mean relative bias for Hb Tacoma samples was < ±6%. The repeatability with all methods was similar for non-variant and Hb Tacoma samples and at highest 4.1% (mean CV% of two levels). The observed interference by Standard F is likely due to two-antibody assay design as Hb Tacoma has been shown to result in conformational change. This interference is clinically significant and highlight the need for better controlling and better understanding hemoglobin variants in HbA1c testing.

A-052 Clinical usefulness of ADAMS A1c HA-8190V automatic switching mode for the HbA1c measurement in Hb variants

Abstract Background High-performance liquid chromatography (HPLC) is widely used as a HbA1c routine assay. However, quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. In this study, we evaluated the clinical utility and analytical performance of new developed ARKRAY ADMAS HA-8190V assay using autoswitch mode, that automatically switches between variant and fast mode depending on patient Hb characteristics, in patients with Hb variant suspected in Korea. Methods The measuring time for HbA1c assay was compared between the HA-8180V fast mode (existing model) and the autoswitch mode of HA-8190V (new model) in 60 normal Hb samples. And the HbA1c measured values was compared bewteen the HA-8180V fast mode and the HA-8190V autoswitch mode in 30 low Hb samples. In addition, flag detection for the abnormal Hb and measured values for 21 Hb variant samples were analyzed using the HA-8180V fast mode and the HA-8190V autoswitch mode. Results It took 50.8 minutes and 39.1 minute to measure 60 normal Hb samples by HA-8180V fast mode and HA-8190V autoswitching mode, respectively. The values could not be measured at the HA-8180V fast mode for 7 of 30 low Hb samples, whereas all samples could be measured at HA-8190V autoswitching mode. For 21 Hb variant samples, HA-8180V fast mode showed abnormal flag detections for only 14 samples, but HA-8190V autoswitch mode reported abnormal variant flags for 20 samples. In the result accuracy evaluation (% difference) based on capillary electrophoresis HbA1c assay (Sebia, Lisses, France) in the 21 Hb variant samples, the % difference of HA-8190 V autoswitch mode was 3.9%, which was superior to HA-8180V fast mode of -11.65%. Conclusions Autoswitch mode of The HA-8190V (automatically switch between variant and fast mode based on patient Hb characteristics) showed more accurate flag detection and HbA1c measurements in patients with Hb variants, along with shorter test time and manual reduction.

A comprehensive review on fructosyl peptide oxidase as an important enzyme for present hemoglobin A1c assays.

Glycated proteins are generated by binding of glucose to the proteins in blood stream through a nonenzymatic reaction. Hemoglobin A1c (HbA1c) is a glycated protein with glucose at the N-terminal of β-chain. HbA1c is extensively used as an indicator for assessing the blood glucose concentration in diabetes patients. There are different conventional clinical methods for the detection of HbA1c. However, enzymatic detection method has newly obtained great attention for its high precision and cost-effectiveness. Today, fructosyl peptide oxidase (FPOX) plays a key role in the enzymatic measurement of HbA1c, and different companies have marketed HbA1c assay systems based on FPOX. Recent investigations show that FPOX could be used in assaying HbA1 without requiring HbA1c primary digestion. It could also be applied as a biosensor for HbA1c detection. In this review, we have discussed the recent improvements of FPOX properties, different methods of FPOX purification, solubility, and immobilization, and also the use of FPOX in HbA1c biosensors.

Primary care monitoring of HbA1c tests in type 2 diabetic patients in Northern France and impact of the successive COVID-19 pandemic containments

BackgroundFrench health authorities recommend the testing of HbA1c every 3 to 6 months in patients with diabetes. The successive containments linked to the SARSCoV-2 pandemic may have had a profound impact on the follow-up of diabetic patients in primary care. The objective of this study was to investigate the effect of containments on the volume of HbA1c assays and on HbA1c values of type 2 diabetic patients monitored in primary care in Northern France compared to usual seasonal variations. MethodsEpidemiological study of a multicentre retrospective cohort, collecting the number and the value of HbA1c assays from type 2 diabetic patients, carried out in 73 private medical analysis laboratories in Northern France region between October 1, 2018 and October 31, 2022. ResultsA total of 196,744 patients and 828,037 tests were included. The first and third containments were associated with a significant decrease in the mean number of performed HbA1c tests, the decrease in the 2nd containment did not reach significance. We observed a significant decrease in HbA1c testing during the winter holiday season and the summer months. The variations in HbA1c values were not substantial compared to seasonal variations.

Changes in screening, diagnosis, management, and outcomes of gestational diabetes during the COVID-19 pandemic: A systematic review

BackgroundGestational diabetes mellitus (GDM) is the most common medical complication of pregnancy, and it can lead to complications for the mother and the infant/fetus. This was especially evident during the COVID-19 pandemic. Therefore, the present systematic review aimed to describe the changes in screening, diagnosis, management, and outcomes of gestational diabetes during the COVID-19 pandemic. MethodsThe systematic review was conducted from December 2019 until January 1, 2022. To find articles related to the purpose of the study, PubMed, Scopus, Web of Science, and WHO were searched using relevant and validated keywords using MeSH/Emtree. ResultsIn total, 675 entries were ascertained from the database inquiry, and 17 scholarly works were deemed suitable for inclusion in the final review. The salient conclusions derived from this review were as follows: (a) During the COVID-19 pandemic, there was a significant decrease in the use of OGTTs and a rise in the use of HbA1c assays for both GDM screening and diagnosing. (b) A predominant number of physicians incorporated some variation of telemedicine to remotely supervise and conduct follow-up evaluations of patients with GDM. Various strategies are presented for the provision of prenatal care to women afflicted with GDM, such as concentrating on high-risk demographics, the initiation of lifestyle modifications at early stages, and the implementation of remote patient monitoring techniques. The 'single test procedure' is identified as the most suitable for the preliminary screening of GDM. The OGTT should be assigned clinical precedence in patients at high risk during the ongoing COVID-19 pandemic. Additionally, Medical Nutrition Therapy (MNT) was established as the primary management strategy, and the most influential determinant of the transition from dietary adjustments to pharmacotherapy was the Fasting Blood Glucose (FBG) levels during the second trimester. ConclusionSuggested strategies for GDM screening and management during the pandemic integrated into routine antenatal care, emphasized the importance of remote diabetes education and technology utilization during health emergencies.

Verification of analytical performance of the HbA1c assay method by CAPILLARYS 3 in the biochemistry laboratory

Verification of analytical performance of the HbA1c assay method by CAPILLARYS 3 in the biochemistry laboratory

Longitudinal assessment of HbA1c assay performance over a 4-year period: Insights from Thai participants in the European HbA1c trial

Longitudinal assessment of HbA1c assay performance over a 4-year period: Insights from Thai participants in the European HbA1c trial

Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa

BackgroundHyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa.MethodsWe performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2–3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders.ResultsA total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8–6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9–10.6).ConclusionMaternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.

Impact of haemoglobin variants on the diagnostic sensitivity of glycated haemoglobin (HbA1c) assay methodologies in sub-Saharan Africa: a laboratory-based method validation study.

the utility of glycated haemoglobin (HbA1c) for the diagnosis and monitoring of diabetes in sub-Saharan Africa is uncertain due to limited data on the performance of the available HbA1c assay methods in this population, which has a high prevalence of haemoglobin variants. We aimed to compare the diagnostic accuracy of the major HbA1c methodologies (Boronate Affinity, Capillary Electrophoresis, High Performance Liquid Chromatography, Immunoassay) in an African population, and assess the impact of the common haemoglobin variant HbAS (sickle cell trait). whole blood samples were obtained from 182 individuals living with type 2 diabetes in Uganda. HbA1c values for each method were compared to average glucose measured over 14 days by continuous glucose monitoring (CGM). To determine concordance, the three HbA1c assay methods were compared to the capillary electrophoresis method. there was a strong correlation between CGM average glucose levels and all four HbA1c methodologies (r=0.81-0.89) which did not differ in those with and without HbAS (present in 37/182 participants). The presence of HbAS did not alter the relationship between HbA1c and CGM glucose for any assay (p for interaction >0.2 for all methods). Diagnostic accuracy for CGM average glucose thresholds of 7 and 10mmol/L was similar across methods (area under the receiver operating characteristic curve 0.80-0.84 and 0.76-0.84 respectively). The maximum bias between the HbA1c assay methodologies was 2 mmol/mol (2.07%). all major HbA1c technologies offer accurate and comparable HbA1c measurement even in this population with high prevalence of haemoglobin variants.

Rapid haemoglobin A and S quantification using Tosoh HLC-723G8 in variant mode for patients with sickle cell disease.

The management of life-threatening complications in patients with sickle cell disease (SCD) requires an accurate and reproducible quantification of haemoglobin A (HbA) and S (HbS) with a short turnaround time and 24-7 availability. We propose a novel method for quantifying HbA and HbS using the glycated haemoglobin (HbA1c) assay on a Tosoh HLC-723G8 (G8) analyser in variant mode. HbA and HbS results obtained using our method highly correlated with results obtained using a reference method (r > 0.99 for 124 samples of patients with SCD or sickle cell trait). Our method met laboratory requirements for linearity (coefficient of variation [CV] and bias <5%), between-run and within-run reproducibility (CV <10%) and carryover (<0.5%) over the range of HbS and HbA values expected in a therapeutic context. Using the G8 analyser in variant mode is viable for monitoring HbA and HbS concentrations in dire situations. This method is easy to use, quick (1.6min per sample), and automatable and produces highly reproducible results without significant bias. Finally, it does not require modifications to the analytical pipeline recommended by the supplier, enabling a 24-7 availability without disrupting routine monitoring of HbA1c in the laboratory.

Advancing Hematological Point-of-Care Diagnostics: Development and Multi-Site Evaluation of a Novel AI-Enabled Diagnostic Device for CBC Analysis with Differential

Introduction: A complete blood count (CBC) with differential is a routine blood test that provides essential health information that is fundamental for maintaining wellness. While many other routine tests can be run in Point of Care (POC) settings, a CBC with differential is largely confined to central laboratory testing environments. Truvian is in late-stage development of a fully automated device that runs a TruWellness Panel (TM) incorporating all routine tests - a CBC with 3-part differential, comprehensive metabolic panel (CMP), lipid panel, HbA1c and TSH in a single run with 300uL of whole blood. This device incorporates high-throughput cell imaging, Computer Vision (CV) and Artificial Intelligence (AI), including machine learning and deep learning, for on board CBC analysis with 3-part and 5-part differentials. Here, we summarize our development and evaluation of the AI-enabled CBC sub-panel through method comparison studies. Methods: An AI-Enabled 5-part white blood cell (WBC) differential was developed using transfer learning. WBC cells were detected through classical object detection algorithms and extracted from fluorescent images of normal donor blood samples acquired on the Truvian device. Each cell in the set was classified by hematopathologists into one of five categories - Neutrophil, Lymphocyte, Monocyte, Eosinophil, and Basophil - to train a deep learning model. The algorithm currently outputs the data in a 3-part differential format (neutrophils, lymphocytes and “others”) with refinement of the full 5-part differential in progress. The final training dataset consisted of ~2000 - 5000 cells in each class. The training set was divided into training (80%) and test (20%) datasets. Data augmentation techniques were leveraged to improve model invariance to cell orientation and reduce the risk of overfitting. Performance of each iteration of the algorithm was assessed using accuracy of the model on test data. Following incorporation of the algorithm into Truvian's comprehensive and automated blood testing platform, comparability between an external reference laboratory and Truvian's system was performed. Samples from over 150 donors were measured and analytical concordance was evaluated by Passing-Bablok regression, and bias was evaluated using the TOST equivalency test. Results: WBC differential models were improved over a two-year period to incorporate cell image refinement associated with hardware and software iterations. The final algorithm was able to accurately detect and differentiate WBCs into 3 main categories: neutrophils, lymphocytes, and “others” (monocytes, eosinophils, and basophils). Neutrophils, lymphocytes, and “others” demonstrated R correlations of 0.98, 0.96 and 0.49 respectively. Slopes of 1.0 were observed for both neutrophils and lymphocytes while “others” had a slope of 1.37. Intercepts ranged from -0.07 to 0.04 x10 3 cells/μL for the various cell classes. The RBC, WBC and platelet cell counting algorithms were able to produce excellent correlation compared to predicate devices with correlation coefficients ≥ 0.95 and slopes between 0.96 to 1.03. Conclusions: In conclusion, this novel diagnostic device represents a breakthrough in point of care diagnostics. The compact, fully automated blood diagnostic device can run a CMP, lipid panel, CBC with 3-part differential, HbA1c and TSH assays simultaneously. By incorporating Computer Vision algorithms for cell detection and AI techniques such as machine and deep learning for differentiation on board the instrument, it offers an efficient tool for accurate and precise CBC analysis with 3-part differential at the point-of-action. Further development and refinement of the differential algorithm is currently underway.

THU253 The Hemoglobin Wayne Variant And Association With Falsely Elevated HbA1c

Abstract Disclosure: N. Mulpuri: None. A. Bryant: None. D. Shahin: None. K. Soe: None. Background: Hemoglobin Wayne (Hb Wayne) is a rare, silent alpha chain variant caused by a frameshift mutation in the HbA2 gene. Although clinically silent, this mutation falsely elevates HbA1c values. Clinical cases: We are presenting three cases of Hb Wayne patients referred to our diabetes clinic within the last 5 years. All three cases were Caucasian-American males diagnosed with uncontrolled diabetes based on high HbA1c values of ranging from 10.1-10.6 %. One of the patients was initially started on metformin while the other patients’ treatment plan included dietary and lifestyle modifications. Review of the labs showed that renal function, complete blood count and fasting plasma glucose were within the normal range. High HbA1c value was noted by routine screening lab without having any symptoms related to DM or features of insulin resistance. The discrepancy between high HbA1c values and other glycemic index parameters (serum glucose and FSBG values) was noted. Subsequently, further work up was done (repeat HbA1c with different assay and fructosamine) to verify the diagnosis of uncontrolled DM. Fructosamine levels and repeat HbA1c with a different assay (enzymatic assay at Quest lab) were normal. Hemoglobin electrophoresis confirmed presence of an abnormal alpha variant consistent with Hb Wayne. The patients were reassured and educated about this Hb variant, and no further treatment for DM was pursued. Conclusion: Rare hemolgobinopathies may be more common than previously expected as they can be clinically silent and easily overlooked. While HbA1c has been an important clinical tool for diagnosis and management of diabetes, clinicians should look for underlying reasons which can affect HbA1c assay if there is any discrepancy between HbA1c, FSBG and plasma glucose values. The laboratory at our institution uses cation- exchange High Performance Liquid Chromatography method (Bio-Rad D-100 instrument) resulting in falsely high HbA1c values. Some hemoglobinopathies can affect the widely used HbA1c testing method such as CE-HPLC. The impact on HbA1c values will differ depending on hemoglobin variant and specific method and assay used. Given the limitations of HbA1c testing, clinicians should avoid relying heavily on HbA1c values in management and diagnosis of diabetes. It is vital that clinicians use their clinical judgment to correlate HbA1c with other clinical parameters such as continuous glucose monitoring data, glycated albumin,1,5 anhydroglucitrol (1,5 –AG), fingerstick blood glucose, plasma glucose and fructosamine values. Presentation: Thursday, June 15, 2023

B-034 Evaluation of the Analytical Performance of Sebia CAPI 3 HbA1c Assay

Abstract Background HbA1c has been the most important marker for glycemic control and for the diagnosis of diabetes mellitus. The NGSP has invested significant efforts in the standardization of the HbA1c assays, and several analytical methods have been developed. We evaluated the analytical performance of the Sebia CAPI 3 HbA1c assay, which is determined by capillary electrophoresis. Additionally, samples with and without hemoglobin variants are analyzed, and results are compared to two HPLC-based methods. Methods Control materials are used in the precision study, which are included in the Sebia CAPI 3 HbA1c kit (Lisses, France). Linearity study is assessed with the linearity materials from LGC Maine Standards (Cumberland Foreside, ME). Carryover is determined by the EP Evaluator (Colchester, VT) with total 21 aliquots of a high and a low HbA1c sample assayed in a specific order. Accuracy study is determined by whole blood patient samples without hemoglobin variants (n = 40) and with hemoglobin variants (n = 8, mostly with Hb S of 30–40%). Results from Sebia CAPI 3 are compared to the current laboratory method (BioRad Variant II Turbo) (Hercules, CA) and the TOSOH G8 (Tokyo, Japan). Both are HPLC-based methods. Results The within-run precision at a mean of 5.5% HbA1c has a CV at 1% (n = 24), and the between-run precision at the level of 5.5% and 8.7% HbA1c has a CV at 1% (n = 20) and 2% (n = 20), respectively. Linearity study demonstrates the analytical measuring range is between 3.1% and 20.8%, although each laboratory might establish its own clinical reportable range. Carryover is passed based on the automatically calculated error limit in EP Evaluator (3 times the SD of the Low-Low results). The accuracy study shows the Sebia results correlate well with percent bias at 2% for BioRad Variant II Turbo and 3% for TOSOH G8 in samples with (n = 8) and without (n = 40) hemoglobin variants. Conclusion The Sebia CAPI 3 HbA1c assay is based on capillary electrophoresis principle, which is a recognized method by NGSP. The assay has demonstrated good precision, a wide analytical measuring range and minimum carryover. The results are comparable to two HPLC-based methods and are well within the total allowable error of 6% by NGSP in samples with and without hemoglobin variant.

A-142 Comparison of Alinity c Hemoglobin A1c Immunoassay with Premier Hb9210 Automated HPLC Assay: Very Few Patients May be Outside Reportable Range Using Alinity c.

Abstract Background Hemoglobin A1c (HbA1c; glycosylated hemoglobin) is used for diagnosis and monitoring of patients with diabetes. In the clinical laboratory both immunoassays and high-performance liquid chromatography (HPLC) based tests are available for such measurement. We use Premier Hb9210 analyzer (HPLC method; Trinity Biotech, Jamestown, NY) for measuring HBA1c in whole blood. As our laboratory is transitioning to Abbott chemistry systems, we compared HbA1c values obtained by the Alinity c and Premier Hb9210. Methods The Premier Hb9210 analyzer is based on boronate affinity high performance liquid chromatography with output in 66 sec. The analytical measurement range is 3.8 to 18.5% although values as low as 2% can be reported by the analyzer but result may not be accurate. The Alinity c Hemoglobin A1c assay measures both total hemoglobin and HbA1c (enzymatic assay) in whole blood and then calculates %HbA1c. The analytical measurement range of this assay is 4 to 14% of HbA1c. Specimens cannot be diluted for Alinity c HbA1c measurement. Results Alinity c HbA1c has excellent total precision (0.4% at HbA1c of 5.1% and 0.25% at Hb A1c of 9.4%). In contrast, Premier HB9210 has total precision of 1.89% at HbA1c of 5.5% and 1.81% at HbA1c of 8.4%. However, analytical measurement range of Premier HB9219 is slightly wider compared Alinity c assay. Plotting HbA1c results obtained by the Premier Hb9210 analyzer in the x-axis and the corresponding values obtained by the Alinity c assay, we observed the following regression equation: y = 0.9499 x + 0.1108 ( n = 50, 0.99). The 95% confidence interval of the slope was 0.9241 to 0.9757. Rarely, we get specimen where HbA1c is between 3.8 and 4.0% (42 specimens out of 52 803 between 2/7/22 to 2/7/23; 0.08%) or above 14% (174 specimens out of 52 802; same period; 0.33%) and these specimens would not produce any result with Alinity c assay. We recently observed HbA1c result of 2.4 % in a sickle cell patient (reported as &amp;lt;3.8% per our lab policy). Discussion Our result indicates that HbA1c immunoassay on the Alinity c analyzer showed values comparable to HPLC method. However, for very few patients HbA1c may exceed 14% due to uncontrollable diabetes. Because specimen cannot be diluted, real value could not be measured using Alinity c but can be measured by the HPLC method. Conclusions We conclude that HbA1c assay on the Alinity c analyzer is a viable alternative to HPLC for measuring HbA1c in clinical laboratory. However, for very few patients (sickle cell trait, uncontrolled diabetes), HbA1c may be outside the range of Alinity c, requiring HPLC analysis.

A-101 Assessing Glycemic Control in Potential Blood Donor at the Blood Bank of the University College Hospital, Ibadan, Nigeria

Abstract Background Voluntary blood donation exercise remains one the safest means of sourcing for blood product made available for patients. However, there are several eligibility criteria put in place before a prospective donor can be accepted for donation exercise. One of the eligibility criteria not commonly considered is the glycemic control of a donor. This is because pooly controlled diabetes being treated with insulin or a patent with type 1 Dm is considered unfit for blood donation. This study carried out was to determine gycemic control of the prospective donors by assaying their HBA1C levels before blood donation at the blood bank of the university college hospital, Ibadan, Nigeria. Methods Venous blood of the prospective donors was collected during the screening exercise that precedes blood donation to determine eligibility. The blood was for the assay of HBA1C was collected into EDTA bottle and analysed using spectrophometric method. A total number of 184 prospective donors were screened within a period of three weeks. Any result that falls between 4.0%–5.6% was considered normal, 5.7%–6.4% was considered Pre-diabetic while results that are greater than 6.5% were considered diabetic and likely not fit for blood donation. Results A total number of 184 apparently healthy young adult between the ages of 19 and 45 years were screened. Out of the 184 prospective donors, 42 (22.8%) of the population were female, the remaining 142 (77.2%) were male. I56 (84.7%) of the population screened had normal gycemic control between 4.0%–5.6% while 20 (15.2%) of the population had a pre-diabetic results (5.7%–6.4%). The reaming 2 (1.1%) prospective donors had poor glycemic control (&amp;gt;6.5%). This suggests that most of the donors had good glycemic control. Conclusion As much as a good attention is placed on other eligibility criteria for blood donation attention should also be placed on the glycemic control of donor for the safety of both the donor and the recipients of blood products.

B-047 Performance Evaluation of Enzymatic HbA1c Assay on Newly Launched Mindray BS-600M Chemistry Analyzer

Abstract Background HbA1c has important reference value in risk stratification, diagnosis, therapeutic monitoring and drug selection for diabetic patients. Therefore, the ability to detect HbA1c has attracted much attention. This study was designed to evaluate the performance of the enzymatic HbA1c assay on a newly launched Mindray BS-600M chemistry analyzer, which can be used to measure whole blood samples directly after mixing without centrifugation. Methods Total 309 clinical samples (EDTA anticoagulation) were analyzed using Mindray BS-600M (enzymatic method), Tosoh G8 (HPLC method) and Roche c501 (immunoassay method) analyzers for the performance comparison. And also, the analytical performance of BS-600M, such as precision, accuracy, linearity, interference of conventional interferents, hemoglobin variants, hemoglobin derivatives and common drugs, were evaluated using other fresh whole blood samples, eight frozen calibrators (IFCC) and forty frozen venous whole blood samples (NGSP). Results The within-run and between-run precision of the enzymatic method for HbA1c determination were less than 1% and linearity of HbA1c (%, NGSP unit) was excellent from 2.96% to 20.23%. The deviations between the results of 48 accuracy samples (IFCC and NGSP) and target values were within ±5%, and the sigma metrics of HbA1c at the high and low concentration levels were between 9.9∼19.0, which belongs to the "world-class" level. The results were excellently correlated with those obtained by Tosoh HLC -723 G8 and Roche Cobas c501 (r = 0.997, 0.992). The regression equations of HbA1c was y = 0.979x + 0.005 (n = 198) between BS-600M and G8 and y = 0.934x + 0.317 (n = 112) between BS-600M and c501. The deviation of interference from conventional interferents (bilirubin, Intralipid, vitamin C), hemoglobin variants (HbS, HbC, HbD, HbE), hemoglobin derivatives (LAlc, CarHb, AcetylatedHb), and commonly used antipyretic analgesics and hypoglycemic drugs were all within ±6%, except for the high level HbF (&amp;gt;10%); and also, BS-600M cannot be applied to severe anemia patients (HGB &amp;lt; 45 g/L), which may lead to falsely high HbA1c results. Conclusion The Mindray BS-600M proved to be a robust and reliable method for HbA1c measurement, and was suitable for routine clinical chemistry or hematology laboratory use. In addition, attention or comment need to be added for samples having high HbF concentrations and severe anemia patients in reporting HbA1c% result.

Comparison of Hb A1c Quantification in the Presence of Hemoglobin Variants of an HPLC Assay with an Enzymatic Assay.

In this study, we evaluated the impact of hemoglobin (Hb) variants on the performance of the Abbott Alinity c and Bio-Rad Variant II Turbo 2.0 HPLC Hb A1c assays. The analytical performance of the Abbott Alinity c Hb A1c (enzymatic) assay was compared to the Bio-Rad Variant II Turbo 2.0 HPLC method using leftover whole blood EDTA samples with and without the presence of a hemoglobin variant. Assay precision was determined from an analysis of controls. Bias was estimated from analysis of a set of 40 samples analyzed by a Tosoh G8 HPLC instrument at the University of Missouri Diabetes Diagnostic Laboratory, an NGSP Secondary Reference Laboratory. Between-day precision was excellent for both methods (<3%). Bias met NGSP criteria of ±5% to target value. Correlation between the Alinity and Bio-Rad methods was good for patient samples without a hemoglobinopathy (y = 1.028x - 0.38, standard error of the estimate (SEE) = 0.16, n = 36, mean bias = -0.22). A total of 700 hemoglobin variant samples were evaluated on the 2 methods. Of the hemoglobin variants, 640/700 gave results on both methods: hemoglobin (Hb) S trait (n = 452), C trait (n = 131), D trait (n = 23), E trait (n = 26), and a mixture of other hemoglobinopathies (n = 8) including beta thalassemia, high hemoglobin F, transfused Hb SC, transfused Hb SD, and transfused Hb SS, or unknown variant. There was good agreement for the 640 Hb variants between the methods with a range of mean differences of -0.10 to +0.06 depending on the variant, but more variability (SEE 0.25 to 0.39). Sixty samples did not have paired results. To our knowledge, this study was the largest investigation of the effect of hemoglobinopathies on the Abbott Alinity c Hb A1c assay. Analytical performance varied depending on the specific hemoglobin variant trait when compared to the Bio-Rad Variant II Turbo 2.0 HPLC method.

Optimal glycated hemoglobin A1c value for prediabetes and diabetes in patients with pancreatic diseases.

Some articles suggest that using HbA1c alone for diabetes diagnosis is inappropriate. It requires considerable researches to explore the efficacy of HbA1c for diagnosing hyperglycemia in patients with pancreatic disease. This study analyzed 732 patients, comprising of 331 without pancreatic disease and 401 patients diagnosed with pancreatic diseases. All participants underwent the HbA1c assay and oral glucose tolerance test. Kappa coefficients were calculated to assess agreement between the HbA1c and glucose criteria. The receiver operating characteristic curve (ROC) was used to calculate the optimal HbA1c value. DeLong test was analyzed to compared the aera under curves (AUCs). There were 203 (61.3%) patients with NGT, 78 (23.6%) with prediabetes, and 50 (15.1%) with diabetes in patients without pancreatic diseases. In patients with pancreatic disease, 106 participants were diagnosed with NGT (36.4%), 125 with prediabetes (31.2%), and 130 with diabetes (32.4%). Patients with pancreatic disease exhibited elevated levels of bilirubin, transaminase enzymes, aspartate transaminase, high density lipoprotein cholesterol and total bile acid. The sensitivity and specificity of the HbA1c (6.5%) for diagnosing pancreatic diabetes were 60.8% (95% CI 52.3, 69.3) and 92.6% (95% CI 89.5, 95.7). In prediabetes, the sensitivity and specificity of HbA1c (5.7%) is 53.2% (44.3, 62.0) and 59.6 (51.5, 67.6). The optimal HbA1c value for diagnosing diabetes was 6.0% (AUC = 0.876, 95% CI 0.839, 0.906), with the sensitivity of 83.8% and the specificity of 76.8%. The optimal HbA1c value for the diagnosis of prediabetes was 5.8% (AUC = 0.617, 95% CI: 0.556, 0.675), with the corresponding sensitivity and specificity of 48.0% and 72.6% respectively. The combined tests (HbA1c, 6.0% or FPG, 7.0mmol/L) presented the sensitivity of 85.7% (95% CI 79.1, 91.3)and the specificity of 92.6% (95% CI 87.6, 97.3) in pancreatic diabetes. From our results, the recommended HbA1c by ADA criterion may not be sufficiently sensitive to diagnose hyperglycemia in pancreatic disease. The optimal value of 5.8% and 6.0% improved the accuracy for diagnosing prediabetes and diabetes and should be considered to be applied. Besides, we advocate the combination of HbA1c and FPG test for the diagnosis of diabetes in patients with pancreatic diseases.

The pivotal role of HbA1c assay to detect hemoglobinopathies: A 5-year observational retrospective study in the population of Southern France.

Mobility and migration flows are growing from different countries of the world to European countries, including France and in particular the Mediterranean basin. This study aimed to investigate the presence of hemoglobin (Hb) variants in outpatients/inpatients of the Montpellier Hospital (France) in whom an HbA1c assay had been performed and for which the country of birth had been informed. This is a retrospective study from January 2016 to December 2020 based on all high-performance liquid chromatography (HPLC) chromatograms (Tosoh Bioscience HLC-723G8) having an alarm of suspected Hb variant during HbA1c measurement. The corresponding samples were systematically sent to the hematology laboratory for confirmation and identification of Hb variant. Patient's medical history, clinical and demographic data were extracted from each medical chart. Statistical analyses were performed using XLSTAT® software, version 2016.06.35661. Three hundred sixty-three patients were confirmed with Hb variant exhibiting 17 different Hb profiles, highlighting the pivotal role of glycated hemoglobin (HbA1c) as a detection step. The prevalence of Hb variant in this southern French population was 0.71%, with the highest frequency for the beta-globin variants (n = 342/363; i.e., 94.2%), including the most common: S, C, E, and D in 200/342 (58.5%), 83/342 (24.3%), 29/342 (8.5%), and 11/342 (3.2%), respectively. Among patients with Hb variants, almost half (165/363; i.e., 45.4%) were born in the African continent with a predominance for Morocco (32/165; i.e., 19.3%) and Algeria (29/165; i.e., 17.5%). HbA1c assay is a useful tool to detect Hb variants. Hemoglobinopathies are a public health issue in the current French population which is a multiethnic society. Despite the monocentric nature of our study, we note a high frequency of Hb variants in the south of France, which underlines the importance of screening for Hb variants in the whole population.

954-P: A New Portable HbA1c Meter—Red Blood Cell Deformability–Based HbA1c Test

In the United States, more than 1 in 5 people with diabetes do not know they have diabetes, and they are at higher risk of severe health complications by diabetes management failure. Early diagnosis and management of diabetes through HbA1c monitoring can address these public health issues, but many people still do not benefit from the HbA1c test due to its limited accessibility. Alternatively, a portable HbA1c meter, which lay users can easily use, could be a valuable solution to monitor their HbA1c levels without visiting the doctor. However, the current HbA1c test requires precise sample volume and temperature-sensitive maintenance, reducing its usability for lay users. In this study, as a solution for portable HbA1c meters, we proposed a new HbA1c assay that can be free from sampling error and maintenance by estimating RBC deformability. This novel system employed a microfluidic channel, evaluating RBCs deformability via detecting the velocity of individual RBCs in a fluidic channel with a narrower width than RBC. The results showed that RBC deformability was inversely correlated with HbA1c level and successfully converted the HbA1c level from estimated RBC deformability data. In conclusion, RBC deformability-based HbA1c test has the potential to revolutionize the HbA1c test assay and could benefit individuals beyond the limits of current point-of-care devices. Disclosure E.Park: Board Member; Orange Biomed Ltd., Co. S.Kang: Board Member; Orange Biomed Ltd., Co. U.Ko: Board Member; Orange Biomed Ltd., Co. Funding Orange Biomed Ltd., Co.