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Interference in a glucose dehydrogenase-based glucose meter.

To the Editor:

The US Food and Drug Administration (FDA)1 has issued a second alert to warn of serious errors with certain blood glucose-monitoring strips that use glucose dehydrogenase pyrroloquinoline quinine (GDH-PQQ) methods (1). Various nonglucose sugars, including maltose, galactose, and xylose, increase the glucose concentrations reported by these methods. Nonglucose sugars are present in a variety of pharmaceutical preparations (1), including Extraneal (icodextrin) peritoneal dialysis solution (2) and various immunoglobulin preparations (3). At least 13 deaths associated with erroneous meter measurements of glucose in patients receiving such pharmaceutical preparations have been reported to the FDA.

A 76-year-old man at our institution had 3 blood glucose readings that unexpectedly were >22.2 mmol/L (>400 mg/dL) on apointof-care (POC) testing meter that used a GDH-PQQ method (Roche Accu-Chek Inform). By contrast, glucose measurements made with a hexokinase method (Abbott Architect) at about the same times were in the range of 7.2-11.2 mmol/L (129-202 mg/dL), suggesting the possibility of a positive interference in the POC method. The patient's medication list contained none of the pharmaceutical preparations listed in the FDA alert as producing interference in the POC testing method and none that were known to contain nonglucose sugars.

In a search for other sources of interfering compounds that might contribute to this patient's high POC glucose readings, we investigated his dietary intake. The patient had been receiving Nepro[R] with Carb Steady[R] (NPS), an Abbott Nutrition product that contains, among other ingredients, maltitol and Fibersol[R], a modified maltodextrin. Neither maltitol nor Fibersol was listed in the FDA alert or in the product insert as an interference in the GDH-PQQ method, but consideration of their chemical structures and the method of Fibersol manufacture led us to investigate their possible interference in the GDH-PQQ method.

We obtained a bottle of NPS solution from hospital stores, maltitol from Sigma-Aldrich, and Fibersol from Matsutani America. The latter 2 compounds were dissolved in whole blood from a healthy donor to make stock solutions of 5 g/L, similar to the stated concentration of Fibersol in NPS (approximately 6.25 g/L). Increasing volumes of the resulting maltitol or Fibersol solutions, or of NPS, were added to separate portions of whole blood from the same donor. In all steps that involved dissolving solids or mixing liquids, samples were rocked on a Nutator mixer (BD) for 5 min to ensure homogeneity. Glucose was measured in samples of whole blood by use of the Roche meter and in the separated plasma by the hexokinase method.

Both NPS and Fibersol produced results like those seen in the patient (Fig. 1). As expected, NPS and Fibersol had little effect on the results of the hexokinase method, but each increased the glucose concentration reported by the POC method [P < 0.001, linear model test for homogeneity of slopes, performed with SAS program GLM (SAS Institute)]. The small increase in the hexokinase results probably reflects an effect of glucose from the corn syrup solids in NPS. Fibersol at the highest concentration tested, 830 mg/L (various molecular weights), increased the apparent glucose concentration as measured by the POC method by 3.2 mmol/L (57 mg/ dL), from a baseline value of 4.5 mmol/L (82 mg/dL) to 7.7 mmol/L (139 mg/dL). The second ingredient after water in NPS is "corn syrup solids," which is a glucose polymer made by the controlled depolymerization of corn starch. Much like Fibersol, these corn syrup solids may have an interfering effect on the POC method. Maltitol had no effect on either method.

[FIGURE 1 OMITTED]

Fibersol is produced by a combination of acidification and heating of maltodextrin. The manufacturer states that the minimum content of indigestible material is 90%. Given that the starting material is maltodextrin, which consists of repeating D-glucose units of varying length, it is conceivable that various modified glucose or maltose molecules remain in Fibersol after the manufacturing process and produce the interference observed with the POC method.

We suggest that modified maltodextrins such as Fibersol be added to the list of potential interferences in GDH-PQQ methods for measuring glucose and that a role of modified maltodextrins be considered in cases of unexpectedly high results from POC glucose meters that use GDH-PQQ methods.

Previously published online at DOI: 10.1373/clinchem.2010.143453

Acknowledgments: We thank Dr. James C. Boyd for assistance with statistical analysis.

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Authors' Disclosures of Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:

Employment or Leadership: None declared.

Consultant or Advisory Role: None declared.

Stock Ownership: None declared.

Honoraria: None declared.

Research Funding: D.E. Bruns, Abbott Diagnostics and Siemens.

Expert Testimony: None declared.

Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.

References

(1.) U.S. Food and Drug Administration. Advice for patients: serious errors with certain blood glucose monitoring test strips. Issued August 13, 2009. http://www.fda.gov/MedicalDevices/Safety/ AlertsandNotices/PatientAlerts/ucm177189.htm (Accessed February 2010).

(2.) Flore KM, Delanghe JR. Analytical interferences in point-of-care testing glucometers by icodextrin and its metabolites: an overview. Perit Dial Int 2009;29:377-83.

(3.) Kannan S, Rowland CH, Hockings GI, Tauchmann PM. Intragam can interfere with blood glucose monitoring. Med J Aust 2004;180: 251-2.

Brian N. Kelly [2] *

Doris M. Haverstick [2]

David E. Bruns [2]

[1] Nonstandard abbreviations: FDA, US Food and Drug Administration; GDH-PQQ, glucose dehydrogenase pyrroloquinoline quinine; POC, point of care; NPS, Nepro[R] with Carb Steady[R].

2 Department of Pathology University of Virginia School of Medicine Charlottesville, VA

* Address correspondence to this author at:

Department of Pathology

P.O. Box 800168

University of Virginia

School of Medicine

Charlottesville, VA 22908

E-mail BNK8N@virginia.edu
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Title Annotation:Letters to the Editor
Author:Kelly, Brian N.; Haverstick, Doris M.; Bruns, David E.
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Jun 1, 2010
Words:1034
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