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Introduction

Hemoglobin A1c (HbA1c); Glycohemoglobin; Glycated Hemoglobin; Diabetic Control Index; Glycated Serum Protein (GSP)

Glycohemoglobin (G-Hb) is a normal, minor type of hemoglobin. Glycosylated hemoglobin is formed at a rate proportional to the average glucose concentration by a slow, nonenzymatic process within the red blood cells (RBCs) during their 120-day circulating lifespan. G-Hb is blood glucose bound to hemoglobin. In the presence of hyperglycemia, an increase in G-Hb causes an increase in HbA1c (formed as a result of irreversible attachment of glucose to an amino acid in the β chain of the adult hemoglobin molecule). If the glucose concentration increases because of insulin deficiency, then glycosylation is irreversible.

HbA1c values reflect average blood sugar levels for the 2- to 3-month period before the test. This test provides information for evaluating diabetic treatment modalities (every 3 months), is useful in determining treatment for T1D with acute ketoacidosis, and tracks control of blood glucose in milder cases of diabetes. It can be a valuable adjunct in determining which therapeutic choices and directions (e.g., oral antihypoglycemic agents, insulin, β-cell transplantation) will be most effective. A blood sample can be drawn at any time. The measurement is of particular value for specific groups of patients: children with diabetes; patients with diabetes in whom the renal threshold for glucose is abnormal; patients with unstable T1D in whom blood sugar levels vary markedly from day to day; T2D patients who become pregnant; and persons who, before their scheduled appointments, change their usual habits, dietary, or otherwise, so that their metabolic control appears better than it actually is.

Normal Findings

Results are expressed as percentage of total hemoglobin. Values vary slightly by method and laboratory.

G-Hb: 4.0%–7.0% or 0.04–0.07

HbA1c: 5.6% (39 mmol/mol); 5.7%–6.4% (30–37 mmol/mol) is considered prediabetic range

Clinical Alert

Critical Value
  1. G-Hb: >10.1% (>0.101)

  2. HbA1c: >8.1% (>0.08) corresponds to an estimated average glucose >186 mg/dL (>10.3 mmol/L)

Procedure

  1. Obtain a 5-mL venous blood sample with ethylenediaminetetraacetic acid (EDTA) purple-topped anticoagulant additive. Serum may not be used.

  2. Observe standard precautions. Label the specimen with the patient’s name, date and time of collection, and test(s) ordered. Place the specimen in a biohazard bag.

Clinical Implications

  1. Values are frequently increased in persons with poorly controlled or newly diagnosed diabetes.

  2. With optimal control, the HbA1c moves toward normal levels.

  3. A patient with diabetes who recently comes under good control may still show higher concentrations of glycosylated hemoglobin. This level declines gradually over several months as nearly normal glycosylated hemoglobin replaces older RBCs with higher concentrations.

  4. Increases in glycosylated hemoglobin occur in the following nondiabetic conditions:

    1. Iron-deficiency anemia

    2. Splenectomy

    3. Alcohol toxicity

    4. Lead toxicity

  5. Decreases in HbA1c occur in the following nondiabetic conditions:

    1. Hemolytic anemia

    2. Chronic blood loss

    3. Pregnancy

    4. CKD

Interventions

Pretest Patient Care

  1. Explain test purpose and blood-drawing procedure. Observe standard precautions. Fasting is not required.

  2. Note that this test is not meant for short-term diabetes management; instead, it assesses the efficacy of long-term management modalities over several weeks or months. It is not useful more often than 4–6 weeks.

  3. Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

Posttest Patient Care

  1. Review test outcome, with target HbA1c of less more 5.7%, and counsel patient appropriately for management of diabetes with oral hypoglycemic agents and insulin. If test results are not consistent with clinical findings, check the patient for HbF, which elevates HbA1c results.

  2. Follow guidelines in Chapter 1 regarding safe, effective, informed posttest care.

Clinical Alert

A number of different tests can determine glycosylated hemoglobin levels. The most specific of these measures is HbA1c. There are different expected values for each test. Keep in mind that HbA1 is always 2%–4% higher than HbA1c. When reviewing results, be certain of the specific test used.

Interfering Factors

Interfering Factors (Varies by Method)

  1. Presence of HbF and H causes falsely elevated values.

  2. Presence of HbS, C, E, D, G, and Lepore (autosomal recessive mutation resulting in a hemoglobinopathy) causes falsely decreased values.