This edition of the Annals contains an article by Geberhiwot et al. describing how HbA1c measurement may help avoid unnecessary oral glucose tolerance tests (OGTTs) in the diagnosis of type 2 diabetes. The use of HbA1c to diagnose diabetes is certainly appealing. It would obviate the need for the patient to attend testing while fasting and, if an OGTT was required, would address the problem associated with poor reproducibility of the 2 h glucose value. Thus, from both a patient and health-care provider perspective, it would be a muchmore convenient wayof testing for the disease. There is also an argument that HbA1c testing may be a more physiological assessment of glucose intolerance than the arti¢cial conditions of the OGTT. However, one of the obvious di⁄culties in solely using HbA1c as a substitute for the OGTT is that it compares a single test with a condition which can be diagnosed using two diierent criteria, namely the fasting plasma glucose (FPG) concentration and the 2 h value. We know that in some individuals -such as obese subjects -diabetes is more likely to be diagnosed on the FPG result, while in others -such as the elderly -it is more likely to be due to a diagnostic 2 hvalue. Sowhile the FPG cut-oi of 7.0mmol/L was chosen because it roughly corresponded with a 2 h value of 11.1mmol/L, nearly a third of Europeans with diagnostic 2 h values have ‘normal’ (p6mmol/L) FPGs, simply because they are a less obese population than the ones from which the new diagnostic criteria were established. This in turn means that the utility of HbA1c as a screening test for diabetes could vary depending on the demographics of age or weight in the particular population studied. Not that this has prevented there being numerous previous studies designed to investigate the possibility, or otherwise, of using HbA1c for this purpose. A metaanalysis of 34 studies con¢rmed that while an HbA1c result above the upper reference limit can be relatively speci¢c for glucose intolerance, it is not especially sensitive. In other words, a raised HbA1c is likely to indicate developing or overt glucose intolerance, but a ‘normal’ value does not exclude it. This is consistent with studies into the biological variability of HbA1c, which have found that non-diabetic subjects hover closely around a ‘set point’ within the 4--6% HbA1c reference interval. As a consequence, a subject with a usual HbA1c of 4% would need to abnormally increase his/her glycation rate by 50% to match another nondiabetic subject with an HbA1c of 6%. It is therefore not surprising that there can be overlap between the HbA1c values of diabetes patients with those of nondiabetic subjects. Likewise, it is also not unexpected that a ‘high-normal’ (5.5--6%) HbA1c can predict diabetes onset, since subjects with these results are likely to be a mixture of those who ordinarily have these concentrations together with others who are progressing to diabetes from lower initial values. Undoubtedly aware of these di⁄culties, Geberhiwot et al. have not attempted to use HbA1c as a screening test in its own right, but have rather sought to combine it with FPG to try to avoid unnecessary OGTTs. Eiectively, therefore, they are using glycated haemoglobin as a surrogate for the 2 h glucose concentration. There is certainly evidence that HbA1c correlates at least as well with post-prandial glucose excursions as it does with pre-meal glucose, and, together with the speci¢city of high HbA1c values for diabetes, the test has been used by them to triage the requirement for the laborious OGTT. At least some of the reasons that we are still debating the use of HbA1c in diagnosis (nearly three decades after its proven use in patients with established diabetes) relate to the analytical and inherent limitations of the test. Leaving aside the current HbA1c standardization/harmonization debate, there remain issues around individuals with abnormal haemoglobins and anaemias, especially when the latter is secondary to haemolysis or iron de¢ciency. In addition, from an analytical perspective, HbA1c is still not the most precisely measurable analyte, so an assay showing a 3% coe⁄cient of variation (CV) at the critical 6.0% HbA1c value can show a diierence in excess of 0.7% HbA1c within the same individual. Givenall these hurdles, it is di⁄cult to see howHbA1c will ever supplant (or even complement) the measurement of glucose while the latter test remains the single means by which the diagnosis is decided.To a clinician, near-certainty in making a diagnosis using HbA1c is not certain enough when deciding whether a person will nowhave an illness which has lifelong health, lifestyle and ¢nancial consequences for them. For this situation to change, HbA1c (a marker of glycation) would need to prove itself to be at least as good a predictor of diabetes complications as hyperglycaemia.