Hemoglobin A1c in Diabetes: Panacea or Pointless?

  1. David B. Sacks
  1. 1Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland
  1. Corresponding author: David B. Sacks, sacksdb{at}mail.nih.gov.

Glycation is the nonenzymatic attachment of a monosaccharide to amino groups of proteins. The reaction has been recognized for many years in the food industry, where it is known as browning (also termed the Maillard reaction) and is responsible for the formation of commonly ingested items, such as toast. In patients with diabetes, glucose accumulation results in enhanced glycation of many proteins, both in tissues (e.g., the lens) and in the blood. Of these, glycated hemoglobin (GHb) is by far the most frequently measured in patient care. Hemoglobin (Hb) in healthy adults consists predominantly of HbA, which has 2α- and 2β-chains. Glucose can attach to several amino acid residues in these chains. HbA1c is formed when glucose attaches specifically to the NH2-terminal valine of the β-chain. Formation of HbA1c is essentially irreversible, and its concentration in the blood depends on both the life span of the red blood cell (RBC), which averages ∼120 days, and the blood glucose concentration. Because the rate of formation of HbA1c is directly proportional to the concentration of glucose in the blood, HbA1c represents integrated values for glucose over the preceding 8 to 12 weeks (Table 1).

View this table:
TABLE 1

Selected attributes of HbA1c

CLINICAL VALUE OF HbA1c

Initially described 57 years ago (1), GHb was first reported to be increased in patients with diabetes in the late 1960s (2). The clinical value of GHb was soon realized and the American Diabetes Association (ADA) began encouraging the routine measurement of GHb in all patients with diabetes (3).

The fundamental role of GHb in diabetes was accentuated by the publication in 1993 of the Diabetes Control and Complications Trial (DCCT) (4). The study, which compared intensive to conventional insulin therapy in patients with type 1 diabetes, documented a direct relationship between blood glucose concentrations …

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