An emerging diabetes mellitus diagnosis modality: HbA(1c).

See Article on Page 41-46

Classically, the diagnosis of diabetes has been made using the fasting plasma glucose, random plasma glucose, or a 2-hr 75-g oral glucose tolerance test. There are many problems with the definition of diabetes based on blood glucose levels, such as the high intra-individual biological variability, variability in the collection and storage methods, and difficulty in ensuring a fasting state before measuring the blood glucose [1].

Recently, the hemoglobin A1c (HbA1c) assay has also been recommended for the diagnosis of diabetes. The HbA1c concentration is a good indicator of glycemic control over the previous 8-12 weeks; the time period is dictated by the 120-day lifespan of erythrocytes. HbA1c is used as the standard biomarker for the adequacy of glycemic management since it correlates well with both microvascular and, to a lesser extent, macrovascular complications based on a large epidemiological study [2,3]. In the past, expert committees have rejected the proposed use of HbA1c for the diagnosis of diabetes mainly because of the lack of assay standardization. However, HbA1c assays are now highly standardized, and an international expert committee recommended the use of the HbA1c test to diagnose diabetes, with a threshold of ≥ 6.5%, in 2009 [4]. The American Diabetes Association (ADA) affirmed this decision in 2010. The diagnostic test should be performed using a method that is certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized or traceable to the Diabetes Control and Complications Trial reference assay [5]. An HbA1c cut-off of ≥ 6.5% is associated with an increase in the prevalence of moderate retinopathy [6].

A few attempts to verify the validity of glycated hemoglobin in diagnosing type 2 diabetes mellitus in different ethnic populations have been published [7]. Since many studies have found that ethnicity influences the HbA1c level [8], it is necessary to confirm the utility of HbA1c in different races. Recently, Yu et al. [9] investigated the validity of glycated hemoglobin in diagnosing type 2 diabetes mellitus in 497 Chinese subjects, and checked the fasting plasma glucose, oral glucose tolerance test (OGTT), and HbA1c. In their study, an HbA1c level of 6.5% had a sensitivity of 62.7% and a specificity of 93.5% as a diagnostic tool. They concluded that the optimal cut-off point of HbA1c was 6.3% with a sensitivity of 79.6% and specificity of 82.2%. HbA1c ≥ 6.5% has reasonably good specificity for diagnosing diabetes in Chinese, in concordance with the ADA recommendation [9]. These results, in terms of Asians, are meaningful. Yun et al. [10] also reported on the difference between the HbA1c assay and fasting plasma glucose level for making the diagnosis of diabetes in Korean adults; the kappa index of agreement between the fasting plasma glucose level and HbA1c was 0.50.

Since HbA1c is associated with the risk of diabetes, HbA1c is superior to the glucose level for assessing chronic complications of diabetes and a study of Koreans found agreement between glycosylated hemoglobin and fasting plasma glucose [10]. The 2011 diabetes guidelines of the Korean Diabetes Association (KDA) included using HbA1c ≥ 6.5% for diagnosing diabetes [11].

To date, many studies support the use of glycosylated hemoglobin for diagnosing diabetes. The HbA1c level is a reliable indicator of chronic glycemia and correlates well with the risk of diabetes complications. Nevertheless, HbA1c is also affected by hemoglobinopathies, recent hemolysis, high triglyceride levels, pregnancy, and some drugs, including salicylates and vitamins C and E [12]. In addition, HbA1c does not reflect acute elevations in the glucose level [12]. Clinicians must be aware of these limitations.