Hemoglobin A_1c in Diabetes: Panacea or Pointless?

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. HbA_1c is formed when glucose attaches specifically to the NH₂-terminal valine of the β-chain. Formation of HbA_1c 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 HbA_1c is directly proportional to the concentration of glucose in the blood, HbA_1c represents integrated values for glucose over the preceding 8 to 12 weeks (Table 1).