Glycemic Control and Hemoglobinopathy: When A1C May Not Be Reliable

Abstract

The American Diabetes Association (ADA) recommends hemoglobin A1c (A1C) as the standard laboratory assessment of glycemic control and efficacy of treatment for patients with type 1 or type 2 diabetes.1 Large prospective research trials in patients with type 12 and type 2 diabetes3 have demonstrated that A1C levels are directly related to risk of diabetes complications, such as retinopathy, neuropathy, and nephropathy. However, in some clinical situations, laboratory assessment using the A1C test may provide unreliable information. When an A1C result is inconsistent with a patient's clinical situation, conditions that affect red blood cell lifespan and hemoglobinopathies must be considered as possible causes1,4 because normative values for A1C are based on individuals with a normal hematological profile. Hemoglobin type is inherited. Hemoglobin A (HbA), normal adult hemoglobin, is the most common type. More than 700 forms of hemoglobinopathy or abnormal hemoglobin variants have been reported; sickle cell (HbS) is the most frequently occurring hemoglobin variant in the United States population.5 In sickle cell trait (HbAS), a person inherits a normal HbA gene from one parent and an HbS gene from the other.6 Although its prevalence is highest among African Americans (6–9%),5,7 HbAS may also occur in those of Hispanic, Greek, Italian, and other ethnic groups. In one population, those of non–African-American ethnicity accounted for 11% of people identified as having HbAS.8 It is estimated that more than 2 million people in the United States have HbAS.9 Because of its prevalence and wide ethnic variation, testing for sickle cell and other selected hemoglobinopathies is routinely performed as part of newborn screening programs in the United States. A1C represents the main fraction of hemoglobin bound to glucose (glycohemoglobin) and is normally present at low levels in red blood …