International Federation of Clinical Chemistry and Laboratory MedicineIFCC recommendation on reporting results for blood glucose☆
Introduction
The World Health Organization (WHO) and the American Diabetes Association (ADA) define the diagnosis of diabetes mellitus by at least two times of fasting plasma glucose concentration ≥7.0 mmol/l. As an alternative, a casual plasma glucose concentration ≥11.1 mmol/l in the presence of symptoms or a 2-h post oral glucose tolerance test result ≥11.1 mmol/l suffice to make a definite diagnosis of diabetes mellitus [1], [2]. The new category of “impaired fasting plasma glucose concentration” has a narrower interval of 6.1–6.9 mmol/l than the previous fasting interval of 5.6–7.7 mmol/l between normal and diabetic classifications [3]. The closer diagnostic limits increase the need for precise and accurate results to classify individuals correctly.
Glucose permeates the erythrocyte membrane quickly, by passive transport. Therefore, glucose distributes like water between erythrocytes and plasma. Currently, various types of instruments detect and report fundamentally different glucose quantities. Biosensors for glucose are “direct reading” when they measure glucose directly, i.e., without prior dilution of the sample. The new generation of direct-reading glucose sensors detects the molality of glucose, which is identical in whole blood and plasma, but different from the concentration. Methods requiring sample dilution will produce results equivalent to concentration when calibrated against aqueous standards, because the water concentrations of sample and calibrator are almost identical after dilution. The original intention of the IFCC-SD WGSE was to make a recommendation for direct reading biosensors in blood gas/electrolyte/metabolite analyzers. However, an isolated recommendation would be meaningless and not lead to the goal of commutable results, which requires a consensus on reporting results for all analyzers. Inexpensive instruments with direct-reading biosensors are available for self-monitoring or point of care testing of glucose [4], [5], [6]. For the foreseeable future, the clinical chemistry laboratory is expected to perform glucose determinations by direct reading sensors concurrently with other routine instruments.
Furthermore, the clinical staff in general does not know whether the laboratory reports blood or plasma glucose [7] with a consequent risk of misinterpretation. The two are frequently mistaken and used interchangeably in the clinical literature, despite an average 11% difference in glucose concentration. With the present use of multiple methods providing different results, there is a serious risk of clinical misinterpretation. This document does not discuss sampling site or preanalytical variables, which are other important issues. The American Diabetes Association provides clinical decision limits for the concentration of glucose in plasma, but the World Health Organization in addition provides the concentration of glucose in whole blood [3]. We recommend a constant factor of 1.11 for the conversion between concentration of glucose in blood and the equivalent concentration in plasma, and only reporting the concentration of glucose in plasma to avoid mistakes. The converted result equals the concentration of glucose in plasma when hematocrit and water concentrations are normal. This recommendation includes point of care devices and methods that measure the concentration of glucose in whole blood. The conversion does not eliminate current pre-analytical influences or hematocrit effects, which are specific to certain methods and summarized in Ref. [4]. However, it will provide consistent commutable results, facilitating the classification and care of patients and leading to fewer therapeutic misjudgments.
Section snippets
Activity and molality
Biosensors respond to activity of the pertinent analytes. The activity of glucose is assumed to be equal to molality, with a molal activity coefficient equal to one. Activity (a, without unit) is related to the chemical potential (μ=μ0+RTlna of unit kJ/mol). Molality is amount per unit water mass, m of unit mmol/kg H2O. The relation between m and concentration, c (of unit mmol/l), is m=c/ρH2O. ρH2O is the mass concentration of water (of unit kg/l). Calibration of direct-reading glucose
Active concentration of glucose in normal plasma
We recommend converting and reporting results from all systems and devices using direct-reading glucose biosensors as the active concentration of glucose in normal plasma [10], [11] and using the unit mmol/l. This recommendation is in agreement with that of the ADA [2]. Another reason for choosing plasma rather than whole blood as the system of reference is the independence from hematocrit. The advantage of direct-reading glucose biosensors responding to molality will not be lost. The converted
Concentration
Most current spectrophotometric methods to measure glucose use enzymatic conversion with NADH as coenzyme and absorptiometry at 340 nm. The light absorption and molar absorptivity of NADH permit direct calculation of the glucose concentration after complete reaction, using optimized conditions.
More often, the concentration is determined by a kinetic measurement, comparing sample to standard. The high molar absorptivity of NADH helps to diminish any matrix effect. A kinetic measurement obviates
Plasma versus whole blood
On a concentration basis (amount of glucose per liter of sample), glucose concentration in plasma is higher than glucose in erythrocytes because the water concentration is higher in plasma than erythrocytes. Unlike direct reading glucose biosensors, sensors that measure diluted samples will produce results that depend on the water concentration of the sample. Therefore, biosensors requiring sample dilution will produce different results for blood (or hemolyzed blood) and corresponding plasma.
Conversion of whole blood to plasma equivalent concentration
This IFCC document recommends using a constant factor of 1.11 for converting concentration of glucose in whole blood to concentration in plasma, based on water concentrations in the two sample types. This relationship has been supported experimentally [8], [9]. Some methods to measure glucose may have additional matrix effects [15]. An individual conversion based on hematocrit may introduce additional error [9], besides being less convenient and requiring additional information. The converted
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IFCC Document Stage 1.
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Robert W. Burnett, Hartford, CT, (USA), Paul D'Orazio, Lexington, MA, (USA), Niels Fogh-Andersen
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Corresponding author. E-mail address: [email protected]
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Corresponding author. E-mail address: [email protected]