In vitro determination of hemoglobin A1c for diabetes diagnosis and management: technology update

It is fascinating to consider the analytical improvements that have occurred since glycated hemoglobin was first used in routine clinical laboratories for diabetes monitoring around 1977; at that time methods displayed poor precision, there were no calibrators or material with assayed values for quality control purposes. This review outlines the major improvements in hemoglobin A1c (HbA1c) measurement that have occurred since its introduction, and reflects on the increased importance of this hemoglobin fraction in the monitoring of glycemic control. The use of HbA1c as a diagnostic tool is discussed in addition to its use in monitoring the patient with diabetes; the biochemistry of HbA1c formation is described, and how these changes to the hemoglobin molecule have been used to develop methods to measure this fraction. Standardization of HbA1c is described in detail; the development of the IFCC Reference Measurement Procedure for HbA1c has enabled global standardization to be achieved which has allowed global targets to be set for glycemic control and diagnosis. The importance of factors that may interfere in the measurement of HbA1c are highlighted

Evaluation of Four HbA1c Point-of-Care Devices Using International Quality Targets: Are They Fit for the Purpose?

BACKGROUND: Point-of-care (POC) testing is becoming increasingly valuable in health care delivery, and it is important that the devices used meet the same quality criteria as main laboratory analyzers. While external quality assessment (EQA) provides a great tool for assessing quality, many POC devices are not enrolled in these schemes and standard laboratory evaluations are needed to assess performance. METHODS: The Clinical and Laboratory Standards Institute (CLSI) protocols EP-5 and EP-9 were applied to investigate imprecision, accuracy and bias. We assessed bias using the mean of 4 certified secondary reference measurement procedures (SRMPs). RESULTS: The Afinion2™ and the Quo-Lab had CVs of ≤1.7 and ≤2.4% respectively in IFCC SI units (≤1.2 and ≤1.7% NGSP) and a bias ≤2 mmol/mol (≤0.2% NGSP) at 48 and 75 mmol/mol (6.5 and 9.0% NGSP). Sigma for the Afinion2 was 5.8 and for the Quo-Lab 4.0. Both methods passed the NGSP criteria with 2 instruments when compared with 4 individual SRMPs. The HbA1c 501 had a CV of 3.4% and 2.7% in IFCC SI units (2.1% and 1.7% NGSP) and a bias ≤2.4 mmol/mol (≤0.2% NGSP) and passed the NGSP criteria with 2 instruments compared with 4 individual SRMPs except for instrument 2 compared with the Tosoh G8. Sigma was 2.1. The A1Care had a sigma of 1.4 and failed all criteria mainly due to a high CV (6.2% and 4.1% in IFCC SI units [4.1% and 2.9% NGSP] at 48 and 75 mmol/mol [6.5 and 9.0% NGSP]). CONCLUSIONS: The analytical performance was excellent for the Afinion2 and the Quo-Lab, acceptable for the HbA1c 501 and unacceptable for the A1Care according to different used criteria, demonstrating that whilst performance is improving there are still areas for considerable improvement

HbA1c method performance: The great success story of global standardization

Diagnosing and monitoring the treatment of people with diabetes is a global issue and uses considerable resources in laboratories and clinics worldwide. Hemoglobin A1c (HbA1c) has been the mainstay of monitoring glycemic control in people with diabetes for many years and more recently it has been advocated as a diagnostic tool for type 2 diabetes mellitus (T2DM). Good analytical performance is key to the successful use of any laboratory test, but is critical when using the test to diagnose disease, especially when the potential number of diagnoses could exceed 500 million people. Very small variations in bias or increased imprecision could lead to either a missed diagnosis or overdiagnosis of the disease and given the scale of the global disease burden, this could mean erroneous categorization of potentially millions of people. Fundamental to good performance of diagnostic testing is standardization, with defined reference materials and measurement procedures. In this review, we discuss the historical steps to first harmonize HbA1c testing, followed by the global standardization efforts and provide an update on the current situation and future goals for HbA1c testing

Frontiers in Academic Ebook Delivery: Deploying the Library Driven Platform

Explore new and emerging initiatives in academic ebook delivery from University of Michigan Press, including their Fulcrum platform, and LYRASIS' work to expand SimplyE to academic titles

A highly anomalous Red-winged Blackbird (Agelaius phoeniceus) song

Red-winged Blackbird (Agelaius phoeniceus) is a highly vocal species with a repertoire of similar, yet acoustically distinct songs. These songs may be altered drastically if, as a nestling, the male goes deaf or becomes acoustically isolated. In deaf Red-winged Blackbirds, these dramatic song alterations may present as songs bearing slight resemblance to the introductory phrase of their normal song. Here, we present a Red-winged Blackbird song observed in Ottawa, Ontario, Canada, that is far outside any normal variation in Red-winged Blackbird songs. Given the individual’s age and the consistency of the anomalous song, it is possible that this is a deaf bird

Are hemoglobin A1c point-of-care analyzers fit for purpose? The story continues

Objectives: Point-of-care (POC) analyzers are playing an increasingly important role in diabetes management but it is essential that we know the performance of these analyzers in order to make appropriate clinical decisions. Whilst there is a growing body of evidence around the more well-known analyzers, there are many ‘new kids on the block’ with new features, such as displaying the presence of potential Hb-variants, which do not yet have a proven track record. Methods: The study is a comprehensive analytical and usability study of six POC analyzers for HbA1c using Clinical and Laboratory Standards Institute (CLSI) protocols, international quality targets and certified International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Measurement Procedures (SRMP). The study includes precision (EP-5 and EP-15), trueness (EP-9), linearity (EP-6), sample commutability (fresh, frozen and lyophilized), interference of Hb-variants (fresh and frozen samples). Results: Only two of the six analyzers performed to acceptable levels over the range of performance criteria. Hb-variant interference, imprecision or variability between lot numbers are still poor in four of the analyzers. Conclusions: This unique and comprehensive study shows that out of six POC analyzers studied only two (The Lab 001 and Cobas B101) met international quality criteria (IFCC and NGSP), two (A1Care and Innovastar) were borderline and two (QuikReadgo and Allegro) were unacceptable. It is essential that the scientific and clinical community are equipped with this knowledge in order to make sound decisions on the use of these analyzers

The Role of BDNF in Peripheral Nerve Regeneration: Activity-Dependent Treatments and Val66Met

Despite the ability of peripheral nerves to spontaneously regenerate after injury, recovery is generally very poor. The neurotrophins have emerged as an important modulator of axon regeneration, particularly brain derived neurotrophic factor (BDNF). BDNF regulation and signaling, as well as its role in activity-dependent treatments including electrical stimulation, exercise, and optogenetic stimulation are discussed here. The importance of a single nucleotide polymorphism in the BDNF gene, Val66Met, which is present in 30% of the human population and may hinder the efficacy of these treatments in enhancing regeneration after injury is considered. Preliminary data are presented on the effectiveness of one such activity-dependent treatment, electrical stimulation, in enhancing axon regeneration in mice expressing the met allele of the Val66Met polymorphism

Understanding the Use of Sigma Metrics in Hemoglobin A1c Analysis

This study utilizes three unique data sets to demonstrate the state of the art of HbA1c analyzers in a range of settings and compares their performance against the international guidance set by the IFCC task force for HbA1c standardization. The data is used to demonstrate the effect of tightening of those criteria and the study serves as a guide to the practical implementation of the sigma metrics approach in a range of clinical settings

The global impact of the International Federation of Clinical Chemistry and Laboratory Medicine, Education and Management Division: engaging stakeholders and assessing HbA1c quality in a multicentre study across China

Background: Diabetes mellitus is a major global issue and high quality testing is essential for the diagnosis and treatment of the disease. The IFCC Committee for the Education in the Utility of Biomarkers in Diabetes (C-EUBD) plays a global role in improving knowledge and understanding around diabetes testing. This paper describes a multi-stakeholder approach, to improving diagnostic and therapeutic testing for diabetes, using a multicentre study in China as an example of the global impact of the group. Methods: Educational workshops were developed to support the scientific aims of the study in which 30 centres around China received identical, fresh frozen whole blood samples with values assigned using IFCC secondary reference methods and undertook precision (EP-5) and trueness studies. Performance was assessed using sigma metrics. Results: A successful multi-stakeholder group was developed and sustained throughout the study through several educational workshops, which enabled the formation of a long-term collaboration with key opinion leaders and policy makers in China. All 30 centres showed good performance with within and between laboratory coefficient of variations (CVs) below 3% in SI units at both low and high haemoglobin A1c (HbA1c) levels. All individual laboratories met the criteria of a sigma of two or more at a total allowable error (TAE) of 5 mmol/mol (0.46% NGSP). Conclusions: The study led to a successful multi-partner approach to improving diabetes testing in China. All centres involved in the study meeting the published IFCC quality criteria, paving the way for future clinical trials and an expanded role for HbA1c testing across the country

Infrastructure to Improve Beef Business Outcomes in the Queensland Gulf

There are significant economic and environmental issues impacting on the short and long term viability of family-run breeding enterprises in the Queensland Gulf. Falling cattle prices and increased business costs threaten the social and financial well-being of many beef producers. Set stocking and overgrazing combine to reduce native 3P (productive, palatable and perennial) grass frequency and herd productivity. The Ryan family on Greenhills Station at George-town in the Queensland Gulf embarked on a 5 year water and fencing infrastructure development program aiming to improve pasture utilisation, land condition and long term carrying capacity