{'fraction_non_alphanumeric': 0.02460801393728223, 'fraction_numerical': 0.018292682926829267, 'mean_word_length': 4.918814432989691, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Stabilization of glucose in blood samples: out with the old, in with the new

Accurate measurements of plasma glucose are required for diagnosis of diabetes, particularly of gestational diabetes, for which hemoglobin A1c cannot substitute for glucose measurements [1]. While laboratories have improved the measurement procedures for plasma glucose, loss of glucose from blood samples before analysis remains a threat to accuracy of results. The traditional use of sodium fluoride (NaF) alone is unsatisfactory as it does not begin to inhibit glycolysis until 90–120 min have elapsed after blood is collected [2, 3]. The failure of NaF to properly control glycolysis leads to falsely low plasma glucose concentrations and, potentially, failure to detect diabetes. By contrast, the use of blood collection tubes with a low-pH citrate buffer stops glycolysis immediately [4]. An article by Garcia del Pino et al. [5] in this issue of Clinical Chemistry and Laboratory Medicine confirms the simplicity and effectiveness of citric acid as an immediate inhibitor of glycolysis. The authors document significantly lower measured glucose concentrations in NaF samples than in paired citrate tubes (which also had a much lower rate of hemolysis). Importantly, their paper is the first to examine the effect of using the citrate tubes on the rate of diagnosis of diabetes. The effect on diagnosis is a critical issue if we are to move beyond the current state of affairs in which uncontrolled glycolysis introduces error into measurement of glucose and diagnosis of diabetes. The average error in measured glucose when NaF is used as the glycolytic inhibitor ranges between 0.28 and 0.39 mmol/L (5 and 7 mg/dL) in published studies, but the actual error for an individual patient can be as great as 1.1 mmol/L (20 mg/dL) if more than 3 h elapse after blood is drawn before plasma is separated from cells or if the patient has increased white blood cell and platelet counts [4]. Such potential errors are widely unrecognized as a significant source of error in the diagnosis and management of diabetes mellitus and in assessing risk of developing diabetes. Some published reports fail to detect the NaF error. It is essential that any study of glycolysis inhibitors include zero-time reference plasma samples that are placed in an ice slurry immediately after collection and centrifuged within 30 min of collection. If, for example, glucose concentrations in NaF plasma separated within 2 h of collection are compared with serum glucose concentrations in serum separated from cells at the same time as the plasma samples, no difference will be seen. In such studies serum and NaF plasma are undergoing uncontrolled glycolysis at the same rate. Measurements of glucose are used to assess risk of adverse events, such as the risk of developing complications of diabetes or developing diabetes. The cut points for diagnosis of diabetes are based on studies of the risk of developing diabetic retinopathy and other adverse outcomes over the subsequent follow-up period. Errors in glucose measurement obscure the relationship between glucose concentration and outcomes and affect patient management. In 2005 Tirosh et al. [6] reported that higher fasting plasma glucose concentrations within the reference interval were an independent risk factor for type 2 diabetes among young men. A multivariate model revealed a progressively increased risk of eventual type 2 diabetes with progressively higher fasting glucose concentrations within the reference interval, measured at the time of an Israel Defense Forces Staff Periodic Examination. They divided the normal fasting glucose concentrations of 13,163 apparently healthy men into quintiles within the reference interval. The first quintile ranged from 2.78 to 4.5 mmol/L (50–81 mg/dL) and the fifth quintile ranged from 5.28 to 5.5 mmol/L (95–99 mg/dL). The hazard ratio of developing type 2 diabetes was 2.84 among those in the fifth quintile when compared with those in the first quintile. Even those in the second quintile (4.56–4.7 g mmol/L; 82–86 mg/dL) were 1.43 times more likely to develop type 2 diabetes than those in the first quintile. A 0.2 mmol/L (3–4 mg/dL) increase in glucose concentration moved subjects into progressively higher quintiles and a higher risk of developing type 2 diabetes; and a similar decrease moved subjects into progressively lower risk quintiles. Therefore, a measurement error of 1.1 mmol/L (20 mg/dL) secondary to improperly controlled glycolysis would totally eliminate the ability to correctly define the true risk