HbA1c as a Diagnostic Tool for Diabetes Screening and New-Onset Diabetes Prediction

Individuals with A1c ≥5.6% have an increased risk for future diabetes….

Various cutoff levels of hemoglobin A_1c (A1c) have been suggested to screen for diabetes, although more consensus about the best level, especially for different ethnicities, is required. Researchers in South Korea evaluated the usefulness of A1c levels when screening for undiagnosed diabetes and as a predictor of 6-year incident diabetes in a prospective, population-based cohort study.

A total 10,038 participants were recruited from the Ansung-Ansan cohort study. All subjects underwent a 75-g oral glucose tolerance test at baseline and at each biennial follow-up. Excluding subjects with a previous history of diabetes (n = 572), the receiver-operating characteristic curve was used to evaluate the diagnostic accuracy of the A1c cutoff. The Cox proportional hazards model was used to predict diabetes at 6 years.

The results showed that, at baseline, 635 participants (6.8%) had previously undiagnosed diabetes. An A1c cutoff of 5.9% produced the highest sum of sensitivity (68%) and specificity (91%). At 6 years, 895 (10.2%) subjects had developed incident diabetes. An A1c cutoff of 5.6% had the highest sum of sensitivity (59%) and specificity (77%) for the identification of subsequent 6-year incident diabetes. After multivariate adjustment, men with baseline A1c ≥5.6% had a 2.4-fold-increased risk and women had a 3.1-fold-increased risk of new-onset diabetes.

The main finding of this study is that the A1c assay was useful as a screening test for Type 2 diabetes and as a predictor of future diabetes. In the study’s population, an A1c cutoff of 5.9% was able to identify people with undiagnosed diabetes, and individuals with an A1c ≥5.6% had an increased risk for progression to Type 2 diabetes independent of other confounding factors. This was a large, prospective cohort study that used stringent criteria to diagnose diabetes and to evaluate the usefulness of A1c level in diabetes screening and in the prediction of new-onset diabetes. In this homogeneous population based study, we applied the OGTT to all participants and used the same instruments and personnel for all clinical and biochemical assessments during the 6 years.

Use of the A1c level in the diagnosis of or screening for diabetes has been debated for many years. Most A1c assays, such as the National Glycohemoglobin Standardization Program, are standardized, and recent expert committee reports suggest an A1c cutoff of 6.5% for diagnosing diabetes. For screening a general population, the A1c level has several advantages over the currently used FPG concentration or 2-h glucose concentration after an OGTT. The A1c assay does not need a fasting or timed sample. It is a better indicator of chronic glycemic level, has less preanalytic instability, and has a more consistent relationship with diabetic microvascular complications than does FPG concentration. However, concerns remain about the risk of underdiagnosing people with overt diabetes when using an A1c cutoff of 6.5%.

Several cross-sectional studies have evaluated the accuracy of the A1c cutoffs in screening for diabetes. In analysis of the National Health and Nutrition Examination Survey data, Buell et al reported that an A1c level of 5.8% showed the highest sensitivity (86%) and specificity (92%) in identifying undiagnosed diabetes when using FPG concentration as the diagnostic test for Type 2 diabetes. In the current study, the definition of diabetes was based on plasma glucose results from the 75-g OGTT, and the A1c value of 5.9% was appropriate for detecting undiagnosed Type 2 diabetes in this Korean cohort population. In a Japanese study of OGTT results in 1,904 people, an A1c cut point of 5.6% identified undiagnosed Type 2 diabetes, and this value is used as a supplementary diagnostic criterion by the Japanese Diabetes Society. Only a few studies have investigated the utility of A1c level in predicting new onset diabetes. Recent Japanese and French cohort studies reported that A1c level is effective in predicting Type 2 diabetes but was less sensitive and specific than FPG concentration for predicting FPG-defined diabetes. This might be because many people with an abnormal 2-h glucose concentration after an OGTT have a normal FPG concentration. Researchers used OGTT to define diabetes and found that A1C level was independently related to an increased
risk of new-onset diabetes, even in those with IFG at baseline. The predictive value of the A1C level was greater than that of the FPG concentration.

Determining the optimal A1C cutoff for diabetes screening is somewhat arbitrary because the risk of diabetes is continuous over a range of glycemic measures. To maximize the diagnostic efficiency, the optimal A1C cutoff should be considered in balancing both sensitivity and specificity. Despite the A1C cutoff value of 5.6% for identifying individuals with increased risk of future diabetes, as was chosen by the Youden Index, it showed only 31% of the positive predictive value. However, we considered the clinical situation because diabetes is a common disease and the action for prevention is highly beneficial and does relatively little harm to healthy subjects.

Our study has some limitations. All participants were enrolled from Korean rural and urban communities of homogeneous ethnic background, and it is debatable whether these results can be generalized. Although racial differences in A1c level have been suggested, the significance of any differences is not clear, and the use of different A1c values according to ethnicity is not currently recommended.

However, after multivariate adjustment of confounders, A1c level remained as an independent predictor of incident diabetes. In addition, the stringency of our study method and prospective follow-up of a large community based cohort for 6 years make our results stronger than those of other studies.

Diabetes CareFebruary 18, 2011DC_100644