HbA1c for the Diagnosis of Diabetes and Prediabetes: Is It Time for a Mid-Course Correction?

Abstract

An estimated 6.2 million people in the United States have undiagnosed diabetes. The average time between onset and diagnosis of type 2 diabetes is 7 yr (1). Diagnosing diabetes is the first step in assuring that appropriate lifestyle, glycemic, and nonglycemic interventions are implemented (2) to reduce the toll that end-organ complications take on the life of the individual and on the health of the nation. The 2010 American Diabetes Association (ADA) standards of care for diabetes, based largely on the opinion of an international expert committee, added hemoglobin A1c (HbA1c) as diagnostic criteria for diabetes (≥6.5%) and prediabetes (5.7–6.4%) (3, 4). In theory, wider application of this new approach should reduce the delay in diagnosing diabetes by adding a straightforward test to complement fasting glucose and oral glucose tolerance testing. However, if HbA1c is not sensitive, that is, if it does not identify individuals who truly have diabetes, and if its limitations are not fully appreciated by those implementing it, this new approach could fail to achieve this goal or further delay the diagnosis of diabetes. HbA1c has long been used as a marker of glycemic control in established diabetes. In affected patients, the rate of HbA1c formation is a direct function of the average blood glucose concentration. Compared with glucose measurements, the use of HbA1c as a diagnostic test has advantages, including convenience, less day-to-day variability, greater preanalytical stability, and international standardization (3, 4). Disadvantages are: HbA1c is more costly than fasting plasma glucose (FPG), guidelines do not adequately reflect the accuracy of HbA1c measurements available across the nation at the current level of standardization, and more importantly perhaps, it may not correlate adequately with actual glucose levels (5, 6). For more than a decade, it has been recognized that there may be a discordance between HbA1c and other measures of glycemia. The study in this issue of JCEM by Lipska et al. (7) highlights the limitations and strengths of HbA1c as a diagnostic test.