Glucose is unstable in whole blood (1). Fluoride-containing tubes are used to reduce glycolysis, especially when very accurate glucose results are required. Complete inhibition of glycolysis by fluoride can take as long as 4 h, during which time glucose can fall as much as 10 mg/dL (0.6 mmol/L) at room temperature (1), even in samples with normal blood cell counts. This is because fluoride inhibits the enzyme enolase, which acts late in the Embden-Meyerhof pathway, thus allowing the “breakdown” of glucose to intermediate molecules earlier in the glycolytic cycle (2). Is there a better fluoride formulation available that can prevent this problem?
Inclusion of citrate buffer and EDTA in a fluoride tube produces immediate inhibition of glycolysis, with no loss of glucose prior to centrifugation for at least 8 h at 77°F (25°C) (3). Even after 24 h, the loss of glucose is only 1.3 mg/dL (0.07 mmol/L). Hexokinase, which converts glucose to glucose-6-phosphate in the initial step of the glycolytic pathway, is ineffective below pH 5.9, a pH that is achieved by the addition of citrate buffer to the modified fluoride tube. Although the advantage of this tube has been clearly confirmed in the U.S. (4), it remains unavailable for routine use in America.
Some laboratories try to prevent significant glycolysis by separating plasma from cells in the shortest possible timeframe. The World Health Organization suggests this must be done within 30 min, with samples collected in an ice slurry (1). We believe that this is impractical, and there is an urgent need for a better glucose blood tube for obtaining accurate glucose results (5). This is important when the goal is as follows:
To diagnose diabetes (although decision points that were derived using suboptimal samples may need fine-tuning)
To prevent incorrect classification of individual patients
To obtain reliable estimates of the prevalence of diabetes in epidemiological studies
To ensure that biological variation is not overestimated (and inconsistent) because of poor preanalytical procedures
To ensure that glucose reference intervals are not falsely wide because of preanalytical variation
To prevent pseudohypoglycemia, particularly in neonates (for whom the in vitro glycolysis rate is faster than in adults)
To ensure that laboratory results used to assess glucose meters and other point-of-care devices are themselves reliable
To determine, when preanalytical variation is minimized, if the oral glucose tolerance test is more reproducible than is suggested by currently available data
Introduction of citrate-acidified fluoride tubes can solve these problems, thus preventing falsely low laboratory glucose results that may lead to misclassification and mismanagement of patients. Their use for obtaining more reliable laboratory glucose results is overdue.
Acknowledgments
No potential conflicts of interest relevant to this article were reported.
