Pseudohypoglycemia or hyperglycemia caused by interference with self‐monitoring blood glucose measurements in anticancer ascorbic acid therapy

Self-monitoring blood glucose (SMBG) meters are now commonly used in diabetes management. Many drugs, including ascorbic acid, are known to interfere with glucose measurements using these meters. However, so far, misdiagnosis caused by interference has rarely occurred at the conventional doses. Recently, intravenous high-dose ascorbic acid treatment has been widely used in 11,233 patients in 2006 and 8,876 patients in 2008 in the USA as one of the complementary and alternative medicines for infection and fatigue, as well as various cancers. A 71-year-old woman with advanced esophageal cancer and diabetes presented to the Department of Metabolic Medicine, Osaka University Hospital, Suita, Japan, for glycemic control in November 2012. At the first visit, her glycosylated hemoglobin level was 8.8%. SMBG was carried out using the Medisafe meter (TERUMO Corp., Tokyo, Japan) to determine the dosage of regular insulin before every meal. One day, she was given a high ascorbic acid dose (50 g) in another hospital. Her blood ascorbic acid concentration just after administration was 342 lg/mL (normal range 4.7– 17.8 lg/mL), and her blood glucose level determined with the Medisafe meter was below 1.1 mmol/L, which was ‘low’. Simultaneously, glucose levels were measured using the Glucocard meter (ARKRAY Inc., Kyoto, Japan). According to the Glucocard meter, her blood glucose level was above 33.3 mmol/L, which was “high.” She had neither hypoglycemic nor hyperglycemic symptoms. The fasting blood glucose level (9.3 mmol/L) determined with the Medisafe meter 2 days after administration was close to the level (9.2 mmol/L) determined using the intra-hospital laboratory test based on the hexokinase method (QuickautoNeo GLU-HK; SHINO-TEST Corp., Tokyo, Japan) and using an automated analyzer (JCA-BM6050; JEOL Ltd., Tokyo, Japan). Then, the treatment with intravenous high-dose ascorbic acid was discontinued with her consent. We prepared blood samples that contained 4.4 and 11.1 mmol/L glucose, and 0–500 lg/mL ascorbic acid. The glucose levels increased in accordance with the increased ascorbic acid concentrations using the Glucocard meter, whereas they decreased using the Medisafe meter. However, the glucose levels measured using the intrahospital laboratory test did not change in response to any ascorbic acid concentration (Figure 1). The Medisafe meter is based on the colorimetric method, which is applied to several types of Accu-Chek meters (Roche Diagnostics, Mannheim, Germany), whereas the Glucocard meter is based on the electrochemical method, which is applied to many glucose meters, including the One Touch Ultra