Does HLA genotype influence the relative risk of Type 1 diabetes conferred by dietary factors?

Measurement of HbA1c remains the cornerstone of management of glycaemic control in people with diabetes, being the major factor in assessing an individual’s risk of microvascular complications. The need for standardization of measurements, particularly to allow comparison of individual values with the Diabetes Control and Complications (DCCT) and the UK Prospective Diabetes Study (UKPDS) results, and for service audit, benchmarking and quality assurance, remains a crucial issue of world-wide interest and importance. In the UK in 2000, experts agreed that within the limits of knowledge and technical expertise available at the time, as a first step towards standardization, harmonization of results could be achieved by using HbA1c assays which were DCCTtraceable and which reported results comparable to DCCT and UKPDS values [1,2]. Methods currently used to measure HbA1c in clinical practice achieve this by using calibration material whose values have been assigned by the US National Glycohemoglobin Standardisation Program (NGSP). Since the publication of this agreement as a Consensus Statement, there has been a significant shift in the UK to DCCT-aligned assays. Information from the external quality assessment schemes confirms that currently around 80% of UK laboratories participating in the scheme use DCCT-aligned methods. Following similar discussions in the USA, under the auspices of the NGSP, a similar shift has occurred: 62% of laboratories report DCCT-traceable results. The UK Consensus Statement recognized that this procedure was a pragmatic first step and that formal standardization required much more work. The NGSP Clinical Advisory Committee met recently to discuss how to move forward. The signatories to this letter were invited to attend as representatives of the UK Consensus Statement Group (S.M.M.), the International Diabetes Federation (P.D.H.), UKPDS central laboratory (S.E.M.) and The International Federation of Clinical Chemistry (W.G.J.). The International Federation of Clinical Chemistry (IFCC) has developed a specific HbA1c method which has been accepted internationally as the IFCC official Reference Method. Primary reference materials are currently being investigated in the hope that they could be used world-wide as a standardization tool. Clearly, the development of a valid chemical standard is highly desirable. After initial difficulties, in recent unpublished studies, it has been found that the regression line and line obtained between NGSP values and the IFCC Reference Method are now almost parallel. Results obtained with the IFCC standard are approximately 1.5–2.0% HbA1c lower than with NGSP, as might be expected from non-specific interference measured by the method used in the DCCT. Validation of the IFCC standard material continues. From the end of 2003, an EU Directive on the use of in vitro diagnostic equipment (IVD Directive; Directive 98/9/EC) will require that ‘the traceability of values assigned to calibrators and/or control materials must be assured through available reference measurement procedures and/or available reference materials of a higher order’ (Annex I–Essential Requirements. Part A. General Requirements, Clause 3). However, as the IFCC standard material is still under investigation, it would seem precipitous to recommend universal adoption of the IFCC calibration to achieve standardization of HbA1c results at the moment. Long-term evaluation of the stability of the IFCC reference method relationship to the DCCT/UKPDS assay must be ensured if clinicians are to have confidence in it. In addition, whilst it is vitally important in the future to have a chemically specific standardization anchor for HbA1c measurement, it remains equally important that expression of results remains linked to DCCT/UKPDS values. We would therefore strongly endorse for the time being the procedure for HbA1c harmonization described in the 2000 Consensus Statement. The position will be re-evaluated next year by the NGSP and the International Diabetes Federation.