Clinical Indications

Diabetes mellitus is a chronic disorder associated with disturbances in carbohydrate, fat, and protein metabolism characterized by hyperglycemia. It is one of the most prevalent diseases, affecting approximately 24 million individuals in the United States. Long-term treatment of the disease emphasizes control of blood glucose levels to prevent the acute complications of ketosis and hyperglycemia. In addition, long-term complications such as retinopathy, neuropathy, nephropathy, and cardiovascular disease can be minimized if blood glucose levels are effectively controlled.

Hemoglobin A1c (HbA1c) is a result of the nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. The attachment of the hexose molecule occurs continually over the entire life span of the erythrocyte and is dependent on blood glucose concentration and the duration of exposure of the erythrocyte to blood glucose. Therefore, the HbA1c level reflects the mean glucose concentration over the previous period (approximately 8-12 weeks, depending on the individual) and provides a much better indication of long-term glycemic control than blood and urinary glucose determinations. Diabetic patients with very high blood concentrations of glucose have from 2 to 3 times more HbA1c than normal individuals.  

Diagnosis of diabetes includes 1 of the following:

-Fasting plasma glucose of 126 mg/dL or greater

-Symptoms of hyperglycemia and random plasma glucose of 200 mg/dL or greater

-Two-hour glucose of 200 mg/dL or greater during oral glucose tolerance test unless there is unequivocal hyperglycemia, confirmatory testing should be repeated on a different day.

The American Diabetes Association (ADA), International Expert Committee (IEC), and the World Health Organization (WHO) recommend the use of HbA1c to diagnose diabetes, using a threshold of 6.5%. The threshold is based upon sensitivity and specificity data from several studies.

Advantages to using HbA1c for diagnosis include:

-Provides an assessment of chronic hyperglycemia

-Assay standardization efforts from the National Glycohemoglobin Standardization Program (NGSP) have been largely successful and the accuracy of HbA1c is closely monitored by manufacturers and laboratories

-No fasting is necessary

-Intraindividual variability is very low (<2% variation)

-A single test could be used for both diagnosing and monitoring diabetes

When using HbA1c to diagnose diabetes, an elevated HbA1c should be confirmed with a repeat measurement, except in those individuals who are symptomatic with a plasma glucose concentration above 200 mg/dL. Patients who have an HbA1c between 5.7 and 6.4 are considered at increased risk for developing diabetes in the future. (The terms prediabetes, impaired fasting glucose, and impaired glucose tolerance will eventually be phased out by the ADA to eliminate confusion.)

The ADA recommends measurement of HbA1c (typically 3-4 times per year for type 1 and poorly controlled type 2 diabetic patients, and 2 times per year for well-controlled type 2 diabetic patients) to determine whether a patient's metabolic control has remained continuously within the target range.