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Glycated Hemoglobin

Glycated hemoglobin (GHB) testing has assumed a leading role in monitoring the long-term blood glucose levels in diabetics. Through the life of the red blood cell, glucose is bound in a two-stage non-enzymatic reaction at various amino groups on the hemoglobin molecule. The GHB concentration reflects average exposure of hemoglobin to glucose over an extended period.

Ongoing research and product development have made GHB testing a reality in laboratories of all sizes and complexity levels. Before considering adding GHB to your test menu, think about the following questions:

*How much time would current lab staff have to devote to GHB testing?
* Does the laboratory already have an analyzer adaptable to measure GHB?
* Is there space for a dedicated GHB analyzer?
* What are the size and budget limitations for purchasing such equipment?

Technical Background

GHB was first described in 1971 by Trivelli et al in The New England Journal of Medicine. GHB was defined as the fast fraction, eluting first during column chromatography with cation exchange resins. Since then we have learned that GHB may, depending on the testing method, actually consist of HB A1a, HB A1b, and/or HB A1c, and is affected by abnormal hemoglobins such as sickle cell, thalassemia, HBE, and HBF. Whether test results are falsely elevated or depressed depends on the charge properties of the hemoglobin in question. If your patient population includes Asians or Africans, or if you are following a diabetic with a known hemoglobinopathy, be aware of the limitations of the test method in use.

While Trivelli's column method established the clinical value of the GHB assay, the method was too cumbersome for routine use. In the decades that followed, several modifications were devised to reduce interference and increase efficacy. The second generation of testing achieved separation via decanting, rather than passing through a column. Next, HPLC systems with ion exchange resin were employed. Then came electrophoretic separation by IEF, which was specific for HB A1c. More recently, colorimetric methods were developed that could be performed, at least in part, on a variety of chemistry platforms. Soon after, small meters were devised that could measure HB A1c in moments with little sample preparation.

Trivelli's original studies showed GHB to be stable and irreversibly formed, not affected by recent diet. The perfect long-term compliance monitor had been found.

Choosing the Appropriate Method

Which HB A1c method is right for your laboratory? Consider your anticipated test volume, current instrumentation, optimal turn-around-time, and space and time constraints. If your test volume will be low, then a small, inexpensive meter with a relatively high cost per test may be a good choice. If turn-around-time is not an issue or if you would rather not acquire another analyzer, batching HB A1c on your routine chemistry analyzer might be a cost-effective option.

If you expect a high demand for HB A1c testing, consider HPLC. While a significant capital investment, these instruments require little maintenance, offer automated sampling, and provide reliable results in a short period of time. Once loaded, the instrument runs QC and patient samples and prints results while lab staff is busy performing other duties.

Consider these options carefully to find the right GHB solution for your laboratory and for the patients it serves. KnappˇFrazer Consulting is always available to assist in the decision-making process.
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