Screening for Diabetes with A1C: Staring at the Empty Stable

Abstract

Diabetes’ contribution to vascular diseases, chronic renal disease and as a leading cause of blindness obliges us to pay attention to its identification, management and, where possible, its prevention. Metabolicmemoryor the “legacyeffect,” alluded to in thefindings of the 10-year follow-up of the United Kingdom Prospective Diabetes Study (UKPDS), adds emphasis to the need for effective control early in the natural history (1). Therefore, there is little doubt that, with suitable tests, diabetes easily meets the criteria for a condition appropriate for screening strategies (2). Exactlywhat those “suitable tests” should be has been the source of controversy for decades. While measures of plasma glucoseeeither fasting or in an oral glucose tolerance test (OGTT)ehave been viewed as diagnostic gold standards, it is clear that their inherent variability is a major impediment (3). Authorities on diabetes have long pondered the use of glycated hemoglobin (A1C) (whose levels parallel ambient plasma glucose levels) as a diagnostic test for diabetes (4,5). The purported disadvantages over the years, have primarily been difficulties in laboratory standardization of assays and, in some countries, a higher population prevalence of inherited hemoglobinopathies that compromise the A1C’s accuracy so precluding international implementation. The analytic problems were overcome in 2002 through the development of a definitive reference method for A1C, enabling much more consistent reporting of A1C levels between laboratories (6). These developments provided a foundation in 2009 for the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) to jointly recommend acceptance of A1C as a valid screening test (3). The Canadian Diabetes Association (CDA) has recently aligned with the international position with their publication of recommendations in this journal (7). It is noted that the distinct advantages of the A1C overmeasures of plasma glucose include: the lack of need for timing or fasting; correlation with the results of research trials; greater biochemical stability, and reproducibility and familiarity with its use as a management tool (3). Furthermore, the epidemiological studies used to define the diagnostic glucose values also provide the cut-off A1C value that predicts future microvascular complications (8). It is abit strange,however, that theseanalyticproblemshavenever been cited as a barrier to the very practical matter of using A1C as the evidence-based target for the treatment of patients with diabetes. While the actions of the international diabetes associations and CDA in moving to recommend A1C might be lauded for their recognition of pragmatic factors and the balance of advantages and disadvantages, there has also been opposition to the changes (9). A steady stream of publications has added to the discussion on the appropriateness of A1C as a screening tool in a variety of select