Abstract
A consensus paper 1 on worldwide standardization of measurement and reporting of glycated haemoglobin (HbA1c) has been published recently by the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), International Federation of Clinical Chemistry (IFCC) and Laboratory Medicine and the International Diabetes Federation (IDF). This proposal has accepted that the IFCC Reference Measurement procedure 2 should be the international method for calibrating all assays used for the measurement of glycated haemoglobin. The consensus proposed five points, which are reproduced in Box 1.
ADA, EASD, IFCC, IDF 2007 Consensus 1
HbA1c test results should be standardized worldwide, including the reference system and results reporting.
The new IFCC reference system is the only valid anchor to implement standardization of the HbA1c measurement.
HbA1c test results should be standardized worldwide, including the reference system and results reporting. The new IFCC reference system is the only valid anchor to implement standardization of the HbA1c measurement. HbA1c results are to be reported worldwide in IFCC units (mmol/mol) and derived NGSP units (%), using the IFCC-NGSP master equation.
If the ongoing ‘average plasma glucose study’ fulfils its a priori specified criteria, an ADAG value calculated from the HbA1c result will also be reported as an interpretation of the HbA1c results.
Glycaemic goals appearing in clinical guidelines should be expressed as IFCC units, derived NGSP units and as ADAG.
A meeting convened at the request of Dr Sue Roberts, National Director for Diabetes, was held in London on 23 January 2008. Representatives of 18 professional organizations and representatives of the diagnostic industry involved in the management of people with diabetes as well as patients with diabetes (Box 2) attended to discuss these proposals and how they should be incorporated into clinical practice in the UK.
HbA1c test results should be standardized worldwide, including the reference system and results reporting. The new IFCC reference system is the only valid anchor to implement standardization of the HbA1c measurement. HbA1c results are to be reported worldwide in IFCC units (mmol/mol) and derived National Glycohemoglobin Standardization Program (NGSP) units (%), using the IFCC-NGSP master equation.
These two points were universally accepted and, indeed, they were first proposed at an earlier consensus held in London in 2000.
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Professional organizations represented at the London meeting
Association for Clinical Biochemistry
Association of Clinical Pathologists
Association of British Clinical Diabetologists
Australian Association of Clinical Biochemists
British In-Vitro Diagnostics Association
Department of Health of England
Diabetes UK
European Federation of Clinical Chemistry
International Diabetes Foundation
International Federation of Clinical Chemistry and Laboratory Medicine
Primary Care Diabetes Society
Royal College of General Practitioners
Royal College of Nursing
Royal College of Obstetricians and Gynaecologists
Royal College of Pathologists
Royal College of Physicians
UK National External Quality Assessment Scheme (UK NEQAS)
Wales External Quality Assessment Scheme (WEQAS)
There was an agreement that it was necessary for glycated haemoglobin to be standardized to the IFCC Reference Measurement procedure but there was a concern regarding the introduction of a dual reporting system including new units with which patients and clinicians were unfamiliar. It was felt that there was a real risk that patient control would deteriorate due to lack of understanding, particularly with an unheralded change to IFCC units. It was agreed that dual reporting would be necessary for a considerable period until both unitary systems were understood. However, this should only occur after extensive educational programmes had been performed. Moreover, it must be ensured that these programmes will reach all the appropriate health-care professionals as well as patients.
If the ongoing ‘average plasma glucose study’ fulfils its a priori specified criteria, an HbA1c-derived average glucose (ADAG) value calculated from the HbA1c result will also be reported as an interpretation of the HbA1c results.
A report of the preliminary findings of the ADAG study was presented by one of the study investigators.
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Data were presented on approximately two-thirds of the subjects, although it was stated that it was anticipated at this stage that the final results would not be different. The group attending uniformly felt that there was insufficient information regarding entry criteria, study design and data analysis on which to accept any conclusions at this stage and that further studies validating the findings from the ADAG study would be required before implementation could be considered.
The conceptual benefits of reporting glycated haemoglobin in terms that patients understand was accepted for patients who measure their own blood glucose concentrations, despite the fact that no patient survey had been performed to study this aspect. However, there was a concern that it would not be beneficial for the vast majority of patients with diabetes who have type 2 disease and who do not routinely measure capillary glucose.
Moreover, there was a concern that the formula for calculating estimated average glucose (eAG) would give a different value than the capillary (finger-prick) samples used for daily monitoring. Overall, it was felt that due to issues raised about the study design and the clinical applicability of the eAG measurement in practice, it was not possible to consider implementing this recommendation in the UK.
Glycaemic goals appearing in clinical guidelines should be expressed as IFCC units, derived NGSP units and as ADAG.
There was a general agreement that reporting a single measurement in three different formats was considered to be unacceptably complicated.
There was a mention of the need for a consistent international measurement for the monitoring of diabetes in a world with huge population mobility to ensure that all patients would have optimal care.
It was felt that eAG was an interesting concept that had the potential to help patients with diabetes improve their understanding of diabetes and therefore improve their health. Participants recommended that studies of eAG should be performed in the UK and that these studies should include patient populations who have been excluded from ADAG. These include children, pregnant women, the elderly and ethnic populations.
Summary recommendations for the UK
HbA1c test results should be standardized using the new IFCC Reference Measurement procedure.
An extensive education programme should be developed urgently for all health-care professionals and people with diabetes to help the understanding and interpretation of the new IFCC units. Provision of this programme will require considerable resources.
HbA1c results should be reported in both IFCC units (mmol/mol) and derived NGSP units (%) (synonymous with Diabetes Control and Complications Trial [DCCT]), using the IFCC-NGSP master equation for the time being
There is currently insufficient experimental evidence to support the introduction of eAG.
Further research into the individual utility of eAG and of its use in all groups of individuals with diabetes is required in order to determine what role reporting of eAG has in clinical practice.