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Glycolysis inhibitors negatively bias blood glucose measurements: potential impact on the reported prevalence of diabetes mellitus
  1. W S Waring,
  2. L E Evans,
  3. C T Kirkpatrick
  1. Clinical Pharmacology Unit, Roche Products, Welwyn Garden City, UK
  1. Correspondence to:
 Dr W S Waring
 Scottish Poisons Information Bureau, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK; s.waring{at}


Background: Blood glucose concentrations are essential in defining diabetes mellitus. Recent guidelines advocate either of two discrete methods for sample collection and processing. One of these involves addition of glycolysis inhibitors, such as sodium fluoride–potassium oxalate (NaF–KOx) to sample collection tubes, whereas the other requires immediate refrigeration and sample separation.

Aims: To examine whether the choice of the preanalytical process has any impact on subsequent glucose determinations.

Methods: 62 healthy men participated in the study during screening for diabetes. Paired venous blood samples were collected in a serum-gel tube and a tube containing NaF–KOx (both Sarstedt, Leicester, UK). Serum was promptly separated from gel tube samples and refrigerated, whereas NaF–KOx samples were not separated until immediately before analysis. Glucose concentrations were determined using an Olympus AU 2700 analyser incorporating an automated hexokinase method.

Results: Mean (95% CI) glucose concentration in serum-gel tube samples was 5.2 mmol/l (5.0 to 5.4 mmol/l), whereas the concentration in tubes containing NaF–KOx was 4.9 mmol/l (4.8 to 5.1 mmol/l). A negative bias of 0.23 mmol/l (0.16 to 0.30 mmol/l) and relative negative bias of 4.7 % (3.2% to 6.3%) were observed for samples collected in NaF–KOx tubes, consistent with the combined effects of glycolysis and dilution.

Conclusions: Bias associated with the use of NaF–KOx tubes may have a significant impact on the prevalence of fasting hyperglycaemia, according to current diagnostic criteria. The small but significant difference between preanalytical processes should be considered when screening for the presence of diabetes mellitus.

  • NaF–KOx, sodium fluoride–potassium oxalate
  • WHO, World Health Organization

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  • Funding: The costs for this study were met from existing departmental funds held by the Clinical Pharmacology Unit, Roche Pharmaceuticals, Welwyn Garden City, UK.

  • Competing interests: None.