Electrochemical Interferences in BGM

Electrochemical Interferences in Blood Glucose Monitoring

Introduction

Electrochemical interference is anything that changes the current a test strip produces for a reason other than glucose. A blood glucose meter (BGM) converts that current into a number, so extra electrons from another source show up as a falsely high reading [5]. The causes fall into two groups. Some are physical properties of the sample, such as the share of red blood cells; others are substances in the blood that react at the strip [4].

Physical Interferences

The largest physical interference is the Hematocrit Effect. Hematocrit is the percentage of blood volume taken up by red blood cells. Studies of many meters have found that a lower-than-normal hematocrit (below roughly 30 to 35%) tends to give readings above the laboratory value, while a higher-than-normal hematocrit (above 45%) tends to give readings below it [3]. Nobody has settled on a single cause. Proposed explanations include changes in blood viscosity, red cells keeping plasma away from the strip's reaction surface, and slower diffusion [3]. Hematocrit also moves more than people expect: smoking, exercise, pregnancy, time in the mountains and hemodialysis can all shift it [3].

Meters deal with this in different ways. With Roche's Accu-Chek Aviva Plus strips, the meter first sends small alternating-current (AC) signals at four frequencies through the sample, then applies a direct-current (DC) voltage to measure glucose, and combines the two into a result compensated for hematocrit and temperature [6]. That AC approach is one design among several, not something every meter does. Here's what surprised us: in a 2011 laboratory study of 13 meters, the four self-test meters that showed less than 10% bias between the highest and lowest hematocrit levels used either dynamic electrochemistry (BGStar) or conventional "static" electrochemistry (Contour, Glucocard G+ and OneTouch Verio) [3]. The Accu-Chek Aviva tested in that study showed a 23% bias [3]. Those were the meters of 2011, so the study shows how much hematocrit handling varied, not how today's meters rank.

Chemical Interferences

Some substances in blood are redox-active, meaning they can give up electrons at the strip's electrode the way the glucose reaction does. Acetaminophen, vitamin C (ascorbic acid) and uric acid are common examples [5]. When they are oxidized at the electrode, they add current the meter counts as glucose and push the reading up [5]. The size and even the direction of the effect depend on the strip. A 2009 review listed acetaminophen as lowering readings on the glucose oxidase systems it covered, listed ascorbic acid as variable, and said uric acid matters only at very high levels [4]. FDA's 2020 guidance for over-the-counter meters asks manufacturers to test known or potential interferents, maltose and acetaminophen among them, and to evaluate varying hematocrit levels [2].

Manufacturers' main chemical defense is the mediator, the molecule that carries electrons from the enzyme to the electrode. An interfering molecule is one that is electroactive at the sensor's operating potential [5], so a strip that runs at a lower voltage gives fewer substances the chance to react [7]. Hexaammineruthenium(III), a ruthenium complex, lets strips run at a lower operating potential than potassium ferricyanide, the most common mediator in commercial strips; as the authors of one study put it, a lower operating potential generally leads to fewer interferences [7]. That means fewer, not none. Abbott's FreeStyle strips, as their developers described them in 2010, use an osmium mediator with a low formal potential, but the stated reason was to stop current shuttling between the strip's two closely spaced electrodes rather than to screen out interferents [8].

Oxygen is a separate problem for strips that use Glucose Oxidase (GOx). Oxygen competes with the mediator for electrons from the enzyme, and the electrode reads only the mediator [4]. Strips are generally calibrated for the oxygen level of capillary blood. A high-oxygen sample, such as arterial blood or blood from someone on supplemental oxygen, can read falsely low; a low-oxygen sample, such as venous blood, can read falsely high [4]. The same review notes that GOx meters are generally not approved for venous blood, and that glucose dehydrogenase (GDH) meters were more accurate than GOx meters in a high-altitude study [4]. GDH chemistry doesn't depend on dissolved oxygen [5].

Historical Context

GDH-PQQ strips use glucose dehydrogenase with the cofactor pyrroloquinoline quinone. The enzyme also reacts with maltose, xylose and galactose, so these sugars can falsely raise the result and hide a dangerously low blood sugar [1]. From 1997 to 2009, FDA received 13 reports of deaths in which maltose or another non-glucose sugar interfered with GDH-PQQ strips. The deaths occurred in healthcare facilities, and 10 of the 13 patients were receiving Extraneal (icodextrin) peritoneal dialysis solution [1], which the body breaks down mainly into maltose [5]. FDA laid out these risks in an August 2009 public health notification [1].

As of October 2026, many strips use other GDH forms. Accu-Chek Guide strips use FAD-dependent GDH (GDH-FAD) [9][11], and FreeStyle Precision Neo strips use NAD-dependent GDH (GDH-NAD) [10]. The move away from PQQ wasn't complete, though. Roche still lists Accu-Chek Aviva Plus test strips as of October 2026 [11], and those strips use a modified ("mutant") GDH-PQQ [6]. Their FDA clearance summary still names galactose above 15 mg/dL as a cause of overestimated results [6]. A 2017 case report adds a caution about maltose: intravenous immunoglobulin (IVIG) containing maltose spilled onto a patient's hand and produced a falsely high reading on an Accu-Chek Performa meter, which also uses mutant GDH-PQQ [12]. Which meter suits someone on peritoneal dialysis or maltose-containing drugs is a decision for that person's care team.