Laboratory Protocol and Pilot Results for Dynamic Interference Testing of Continuous Glucose Monitoring Sensors

Abstract

Background: Testing the potential influence of interfering substances on the measurement performance of needle sensors for continuous glucose monitoring (CGM) is a challenging task. For proper function, the sensors need an almost stable fluidic environment. Previously published in vitro interference experiments were measuring under static concentration conditons. Our experimental setup allows for interference testing with dynamic changes of the interferent concentrations. Methods: We designed a macrofluidic test stand that is fueled by several high-pressure liquid chromatography (HPLC) pumps generating programmable glucose and/or interferent gradients in phosphate-buffered saline (PBS). After optimizing experimental parameters (channel dimensions, temperature, flow rates, gradient slopes, buffer, pH etc.), we validated the setup using Dexcom G6 (G6) and Freestyle Libre 2 (L2) sensors with/without interferents, and using YSI 2300 Stat plus as the reference glucose device at room temperature. Results: Both sensors tracked the programmed glucose changes. After calibration, G6 results closely matched glucose reference readings, while L2 routinely showed ~50% to 60% lower readings, most likely because of the factory-based calibration and temperature compensation. Gradients of maltose, acetaminophen, and xylose were employed to further validate the setup. As expected, both sensors were not affected by maltose. We confirmed previous findings regarding susceptibility of G6 readings to acetaminophen and L2 readings to xylose. Signals from both sensors are influenced by temperature in a linear fashion. Conclusions: Our experimental in vitro setup and protocol may provide a useful method to dynamically test CGM sensors for interfering substances. This may help to improve the accuracy of future CGM sensor generations.

Miniaturization of an Osmotic Pressure-Based Glucose Sensor for Continuous Intraperitoneal and Subcutaneous Glucose Monitoring by Means of Nanotechnology

“…Based on these results, the miniaturized sensors were now manufactured with inclusion of the active glucose-sensing Concanavalin A/dextran chemistry [17]. When exposing these sensors to dynamic glucose concentration in the fluid around the sensors, changes by using an in vitro dynamic CGM test rig [16], similar osmotic pressure changes were seen as with the previous larger prototypes (Figure 5). Pressure changes were reproducible, and a linear relationship between the sensor signal and varying glucose concentrations in the supernatant was observed.…”

“…The use of CGM systems has hence resulted in a reduced frequency of hypoglycemic and hyperglycemic events, an overall improvement of glycemic control, and an improved quality of life [4][5][6][7][8][9][10][11][12][13]. However, the current glucose sensors need to be replaced every 10 to 14 days, and they have interference and accuracy issues [14][15][16]. In consequence, there is still a medical need for the development of small glucose sensors with improved measurement properties.…”

Perceptions of Continuous Glucose Monitoring Systems in the T1D Exchange Diabetes Registry: Satisfaction, Concerns, and Areas for Future Improvement

“…Given the publicity and abundant literature on substances that interfere with CGM accuracy ( 22 – 27 ), it was surprising that dehydration was selected by respondents (especially those with type 1 diabetes) as having the most impact on accuracy. Published evidence on this topic is limited; in fact, we have been unable to find a specific study describing how hydration levels affect CGM accuracy.…”

“…An increasing number of interferents are being identified, to date including acetaminophen, salicylic acid, galactose, xylose, ascorbic acid, hydroxyurea, mannitol, tetracycline, ethanol, red wine, lisinopril, albuterol, and atenolol ( 18 – 26 ). An elegant in vitro methodology for investigating the impact of single agents or cocktails of potential interferent substances was developed and subsequently validated using the Dexcom G6 and FreeStyle Libre 2 systems ( 27 ). Our current in-depth survey of people with diabetes from the T1D Exchange sought to probe their level of acceptance of and satisfaction with current CGM systems.…”

Drug Interference in Self-Monitoring of Blood Glucose and the Impact on Patient Safety: We Can Only Guard Against What We Are Looking for

“…In the past years, continuous glucose monitoring (CGM) has become an important tool for diabetes management. Interference in CGM is even more complex, 32 in particular because concentrations in the interstitial fluid can be quite different from blood concentrations. More research on interference testing in this context is urgently needed.…”