The concern about vitamin C is not hypothetical. Ascorbic acid, one of the most widely consumed over-the-counter supplements in the world and a natural component of fruits, vegetables, and orange juice, has been shown in previous studies to interfere with some electrochemical glucose sensors. Devices such as the Abbott FreeStyle Libre 2 and Libre 3 have been reported to produce falsely elevated glucose readings in the presence of ascorbic acid, a failure mode that could prompt a user to inject more insulin than needed and slide into severe hypoglycemia. Exercise poses a different challenge: many CGM sensors rely on glucose oxidase, an enzyme that requires oxygen as an electron acceptor, and because oxygen levels in tissue fluctuate during physical activity, readings can drift precisely when people with diabetes need reliable numbers most.

The device at the center of the new study, the iCan i3 CGM (also marketed in Europe as GlucoMen iCan), takes a different biochemical route. Instead of glucose oxidase, its sensor uses flavin adenine dinucleotide-dependent glucose dehydrogenase, or GDH-FAD. Because this enzyme does not use oxygen as an electron acceptor, its catalytic activity is not perturbed by the oxygen swings that accompany exercise. The sensor and its external transmitter are built as a single unit and stream readings to a smartphone app every three minutes over Bluetooth. The device is approved for people aged two years and older with type 1 or type 2 diabetes and is available in roughly one hundred countries across Asia, the Middle East, Europe, and Latin America.

To test whether this chemistry translates into real-world robustness, researchers led by Ronald Brazg at the Rainier Clinical Research Center in Washington State ran a single-center, double-blinded, randomized trial between May and June 2022, registered as NCT05348928. Sixteen adults with type 1 diabetes, aged 18 to 65 and managed with multiple daily injections or an insulin pump, each wore three sensors for the full fifteen-day wear period, two on the abdomen and one on the back of the upper arm. Participants attended three in-clinic visits of roughly eight hours each, at the beginning, middle, and end of the sensor life, during which venous blood was drawn every fifteen minutes and analyzed with a Yellow Springs Instrument 2300 analyzer, the laboratory reference endorsed by the US Food and Drug Administration.

The interference protocol was deliberately demanding. At each visit participants ate two meals designed to produce pronounced glucose excursions, dosing their own insulin as they normally would. At the second and third visits they also performed thirty minutes of moderate exercise on a treadmill or reclining bicycle between the meals. Before the second visit, participants were randomized to swallow 1000 milligrams of ascorbic acid, the standard dose found in most vitamin supplements, before the first meal and exercise at one of those two visits in a cross-over design. Throughout the clinic days the researchers compared hundreds of paired sensor and reference values, calculating agreement rates and the mean absolute and relative differences between the CGM and the YSI reference, both with and without vitamin C and both with and without exercise.

The headline result is one of quiet reassurance. Across the full measurement range of 35 to 450 milligrams per deciliter, 92.0 percent of CGM readings fell within 20 percent of the reference value for glucose above 100 milligrams per deciliter, or within 20 milligrams per deciliter for values at or below that threshold, a performance consistent with integrated CGM boundaries and with data later reported for the same device in a German study. More striking were the interference findings. The overall change in mean absolute difference between the exercise and non-exercise conditions was minus 1.3 milligrams per deciliter, and between the ascorbic acid and non-ascorbic acid conditions minus 1.1 milligrams per deciliter. The corresponding changes in mean absolute relative difference were minus 1.5 percent and minus 1.6 percent. In other words, if anything, accuracy was marginally better under the interference conditions, and none of the shifts were considered clinically meaningful.

The detailed breakdowns reinforced that conclusion. In the hypoglycemic range below 70 milligrams per deciliter, the ascorbic acid condition produced a change in mean absolute difference of minus 3.1 milligrams per deciliter, while in the target range of 70 to 180 and the hyperglycemic range above 180 the mean absolute relative difference changed by minus 1.1 percent and minus 1.7 percent respectively. Surveillance error grid analysis, which maps each paired reading onto a risk surface for clinical decision-making, showed that the vast majority of measurements fell within the no-to-mild risk zones both with and without vitamin C, and no measurements landed in the moderate-to-extreme risk regions. Analyses stratified by dosing sequence and by sex told the same story. Trend accuracy, measured by how well the sensor’s rate-of-change categories matched the reference, was also reasonable, with 61.8 percent concordance in the mildly falling range of minus 1 to 0 milligrams per deciliter per minute.

The authors attribute the resilience to the GDH-FAD chemistry combined with the device’s third-generation sensor architecture. Because the enzyme does not depend on oxygen, the tissue oxygen fluctuations that accompany moderate exercise simply do not enter the electrochemical equation. And because ascorbic acid interferes at the electrode surface in a chemistry-specific way, the different redox mediator system of the iCan sensor appears to sidestep the vulnerability documented for glucose oxidase-based competitors. The contrast with earlier literature is stark: a 2021 review reported a 3.8 percent change in MARD for the Dexcom G6 after thirty minutes of aerobic exercise and a 13.1 percent change for the FreeStyle Libre after forty-five minutes of cycling, whereas the present trial found changes in the opposite direction and of negligible magnitude.

Safety and tolerability were also favorable. All sixteen enrolled participants completed the study. Four adverse events were recorded among two participants, three of them insertion-site reactions such as bleeding and bruising and one a mild gastrointestinal complaint; there were no serious or severe events, insertion pain on a visual analog scale was mild, and only four sensors had to be replaced, three for insertion failure and one for a mid-wear malfunction. Mean sensor wear time was 14.2 days, close to the device’s rated lifespan, and participants lived their normal lives between clinic visits, managing their diabetes with their own usual tools while blinded to the study sensor’s output.

The trial’s limitations are worth keeping in view. Sixteen participants is a small sample, and although recruitment was blind to race, gender, ethnicity, height, weight, and body mass index, a larger and more demographically diverse cohort would strengthen the evidence. The 1000-milligram vitamin C dose matches standard supplements, but total body ascorbic acid from diet varies between individuals, and the study could not account for that background. Interference was also assessed only at defined time points during the laboratory visits rather than continuously in free-living conditions, and the exercise was limited to thirty minutes of moderate intensity on a treadmill or bicycle, leaving open questions about prolonged or vigorous activity. Even so, the study was designed to stress the sensor across the full glycemic range with real meals, real insulin dosing, and a full fifteen-day wear, and it passed those tests. For people with type 1 diabetes who take their vitamin C with breakfast and head to the gym afterward, the message is that this new generation of GDH-FAD-based sensors, at least, can be trusted to keep counting honestly.

Subject of Research: Effects of ascorbic acid and exercise on the accuracy of a GDH-FAD continuous glucose monitoring system in adults with type 1 diabetes

Article Title: Impact of Ascorbic Acid and Exercise on Accuracy of a Glucose Monitoring System with GDH-FAD Technology in Adult Patients with Type 1 Diabetes Mellitus: A Double-Blinded, Randomized Trial

Article References: Brazg, R., Mitchell, T., Fei, J., Zheng, J., Gao, F., Gao, A., Zhu, S., Flacke, F., Shi, L., & Strange, P. (2026). Impact of Ascorbic Acid and Exercise on Accuracy of a Glucose Monitoring System with GDH-FAD Technology in Adult Patients with Type 1 Diabetes Mellitus: A Double-Blinded, Randomized Trial. Diabetes Therapy. https://doi.org/10.1007/s13300-026-01918-9

Image Credits: AI Generated

DOI: 10.1007/s13300-026-01918-9

Keywords: continuous glucose monitoring, type 1 diabetes, ascorbic acid, vitamin C interference, exercise, GDH-FAD, glucose sensor accuracy, MARD, randomized trial, diabetes technology, interstitial glucose, hypoglycemia

To understand why this result is attracting attention, it helps to look at the regulatory asymmetry between the two sides of the Atlantic. In 2018, the United States Food and Drug Administration created the “integrated” CGM, or iCGM, designation, a performance-based regulatory pathway that imposes stringent accuracy and interoperability standards on manufacturers. Devices cleared under this pathway can reliably “integrate” with other digitally connected health technologies, including insulin pumps and smart pens, because regulators have verified their performance across the full measuring range. In Europe, by contrast, CGM systems have traditionally entered the market through CE marking, a process that assesses general safety and performance but has been criticized in the clinical literature as less stringent, less device-specific, and less transparent than the FDA approach. For patients and clinicians, this has meant that two sensors carrying the same CE mark could, in principle, perform very differently.

The eCGM proposal was formulated to address precisely this concern. Largely mirroring the FDA’s iCGM requirements, the eCGM criteria specify accuracy expectations across three glycemic strata, define limits for paired glucose comparisons against laboratory reference measurements, set confidence interval thresholds for proportional agreement, and impose demanding requirements on how the supporting clinical study must be designed. Among these design requirements are a minimum of 100 participants, a majority with type 1 diabetes, sensors drawn from at least three manufacturing lots, the use of laboratory-grade reference analyzers, and crucially a distribution of comparator glucose values in which at least 8 percent fall below 70 mg/dL and at least 5 percent exceed 300 mg/dL. That last requirement is far from trivial: recruiting enough data points at dangerously low and very high glucose levels, while keeping participants safe, is one of the hardest parts of CGM performance testing.

The new analysis, led by Nina Jendrike and Guido Freckmann of the Institut für Diabetes-Technologie Ulm GmbH together with Korean collaborators, assembled a pooled dataset from three clinical investigations to meet these stringent conditions. The first pivotal study, conducted in the Republic of Korea between February and August 2022 with 84 participants, supported national regulatory approval in 2023. A second pivotal study, run in Germany between May and October 2022 with 50 participants, contributed to the CE marking granted in early 2024. Because the two pivotal trials together did not quite reach the glycemic distribution demanded by the eCGM proposal, the team added a post-market clinical follow-up study between October and December 2025, enrolling 30 additional participants specifically to generate supervised hypoglycemic and hyperglycemic excursions, with venous blood sampled as frequently as every five minutes during those episodes.

The resulting pooled dataset comprised 164 participants, of whom 86 percent had type 1 diabetes, half were female, and two-thirds managed their diabetes with multiple daily injections. Across the three studies, 168 primary sensors were worn, and 163 of them yielded 17,655 paired CGM-comparator measurements suitable for the accuracy analysis. Of these pairs, 10.9 percent had reference plasma glucose values below 70 mg/dL and 5.7 percent exceeded 300 mg/dL, comfortably satisfying the eCGM distribution requirements. All CGM readings were retrospectively generated by the manufacturer using the currently marketed optional-calibration algorithm applied to the recorded raw sensor signals, while the statistical analysis itself was carried out independently by the investigators.

The headline numbers are striking. In the hypoglycemic range, where CGM accuracy matters most for safety, approximately 91.0 percent of sensor readings below 70 mg/dL fell within ±15 mg/dL of the paired laboratory value, placing the device at the upper end of the 85.7 to 93.2 percent range reported for FDA-cleared iCGM systems. In the euglycemic range of 70 to 180 mg/dL, 78.6 percent of readings agreed with the comparator within ±15 percent, rising to 84.4 percent in the hyperglycemic range above 180 mg/dL, where competing iCGM devices have reported 85.5 to 92.6 percent. Overall, 90.3 percent of all readings landed within ±20 percent of the reference value across the measuring range, and the pooled mean absolute relative difference, a widely cited accuracy metric known as MARD, came out at 9.5 percent. Consensus Error Grid analysis reinforced the clinical picture: 94.6 percent of readings fell into zone A, meaning no effect on clinical action, 5.4 percent into zone B with little or no effect on outcome, and essentially none into the zones representing meaningful clinical risk.

Beyond raw accuracy, the analysis probed how performance holds up over the sensor’s 15-day wear period, a question of real practical importance since CGM accuracy often drifts at the beginning and end of sensor life. Accuracy was slightly lower during the first three days of wear but then stabilized and remained consistent through day 15, a pattern the authors describe as in line with modern CGM technologies. Kaplan-Meier survival analysis, which included all 168 primary sensors, estimated a 90.2 percent probability that a sensor would survive to the end of its expected 15-day-and-30-minute lifetime, with a mean survival time of 14.4 days. Data availability averaged 99.7 percent, and of the 267 data gaps identified, over 91 percent lasted less than 15 minutes; only two gaps exceeded one hour, both traced to smartphone-related user issues rather than sensor malfunction. Safety findings were similarly reassuring: eight adverse device effects were recorded, all mild and non-serious, consisting of erythema, skin pressure marks, and minor bleeding at insertion sites, all recognized and expected consequences of CGM use.

The authors are careful to situate these results within their limits. The analysis was conducted under controlled clinical conditions, so real-world performance may vary with physiological and environmental factors, and the study population excluded children and pregnant women, meaning results cannot simply be generalized to those vulnerable groups. The pooled dataset, while heterogeneous in study design and population, was also funded by the device manufacturer, which provided the systems and retrospectively generated the CGM readings, although the investigators retained independent control over the statistical analysis and interpretation. The eCGM framework itself remains a proposal rather than a formally established European regulatory requirement, and the authors note that further consensus among clinicians, regulators, and manufacturers will be needed before it can be embedded in official guidance. In parallel, the IFCC Working Group on CGM has developed its own comprehensive guideline aimed at a formal ISO standard, signaling that the regulatory landscape for glucose sensors is consolidating rapidly.

Even with those caveats, the significance of the result is hard to overstate. This is the first time that explicit compliance with the eCGM accuracy criteria has been demonstrated for any CGM system, and notably it was achieved by a device that has not itself received FDA iCGM clearance, a status that would otherwise have implied such compliance. For the roughly millions of Europeans who rely on CGM to steer insulin therapy, the study offers something previously absent from the CE-marking landscape: a transparent, quantified, internationally benchmarked demonstration that a sensor can read glucose accurately enough to dose insulin on, detect hypoglycemia dependably, and feed data continuously to an automated insulin delivery algorithm. As CGM technology becomes the backbone of closed-loop diabetes care, independent verification of the numbers behind those algorithms is not a technicality. It is the foundation on which patient safety, and the next generation of automated diabetes therapy, will be built.

Subject of Research: Clinical performance of the CareSens Air CGM system against the proposed European eCGM accuracy criteria

Article Title: Performance of the i-SENS CareSens Air CGM System in Compliance with the European CGM (eCGM) Clinical Performance Criteria: A Pooled Analysis

Article References: Jendrike, N., Kim, K.-S., Lee, S.-H., Yoo, W. S., Park, C.-Y., Öter, S., Morent, L., Eichenlaub, M., & Freckmann, G. (2026). Performance of the i-SENS CareSens Air CGM System in Compliance with the European CGM (eCGM) Clinical Performance Criteria: A Pooled Analysis. Diabetes Therapy. https://doi.org/10.1007/s13300-026-01917-w

Image Credits: AI Generated

DOI: 10.1007/s13300-026-01917-w

Keywords: continuous glucose monitoring, eCGM, CareSens Air, diabetes technology, sensor accuracy, MARD, insulin dosing, automated insulin delivery, hypoglycemia, CE marking, clinical performance, i-SENS

Completing a marathon with type 1 diabetes is a metabolic balancing act of unusual complexity. Every kilometre of running consumes muscle glycogen and blood glucose, while carbohydrate intake, insulin sensitivity, adrenaline, dehydration and core temperature all push glucose levels in different directions at different times. Too much circulating insulin, or too little carbohydrate on board, risks hypoglycaemia, a dangerous drop in blood sugar that can cause confusion, collapse or worse. Too little insulin risks hyperglycaemia and ketoacidosis. Despite the well-documented health benefits of regular exercise, fear of these low-glucose episodes remains the single biggest barrier to physical activity for people with type 1 diabetes, affecting up to 45 per cent of those living with the condition.

To examine how amateur runners actually manage this challenge, the researchers designed an observational study built around the 2025 Poznań Marathon, a standard 42-kilometre road race. They recruited 20 amateur runners: 10 with type 1 diabetes of at least one year’s duration and 10 controls without diabetes. The two groups were well matched, showing no significant difference in age (a mean of 35.4 years in the diabetes group versus 39.7 years in the controls), and each group contained eight men and two women. Among the runners with type 1 diabetes, the median duration of the condition was 16.5 years and median glycated haemoglobin, a measure of long-term glucose control, stood at 6.4 per cent, indicating generally well-managed diabetes.

Before the race, each runner with type 1 diabetes followed an individualised insulin strategy agreed in advance. The target pre-race glucose range was set at 140 to 200 mg/dL, deliberately above the normal fasting range to create a safety buffer for the exercise-induced drops to come. Runners using multiple daily injections reduced their basal insulin dose by 25 per cent, while those using non-hybrid insulin pumps cut basal delivery by 50 per cent. Participants on hybrid closed-loop systems, which automatically adjust insulin delivery, instead set a target glucose of 150 mg/dL. Five runners used multiple daily injections, three used continuous subcutaneous insulin infusion pumps, and two used automated insulin delivery systems, reflecting the full spectrum of modern insulin therapy.

Glucose was assessed at five checkpoints along the course: the start line, 10 km, 19 km, 30 km and the finish. At each point, capillary glucose was measured with a standard fingerstick glucometer and compared against readings from two different CGM systems, one intermittently scanned and one transmitting in real time. Carbohydrates or insulin were administered as required throughout the race. The researchers also evaluated the accuracy of the CGM devices using mean absolute relative difference, or MARD, a standard metric that expresses the average absolute percentage difference between sensor readings and reference glucose values. The lower the MARD, the more faithfully the sensor tracks true blood glucose.

The headline performance result was striking in its ordinariness. Marathon completion times did not differ significantly between the groups, with a median finishing time of 228 minutes for the runners with type 1 diabetes and 248 minutes for the controls. In other words, with careful preparation, the runners with diabetes were not merely surviving the distance; they were racing it on equal terms. During the race, they consumed a median of 53.5 grams of carbohydrate per hour, equivalent to 2.61 grams per kilogram of body weight across the entire marathon, a fueling rate consistent with general endurance-sport guidance.

The glucose traces themselves told a reassuring story. Median capillary glucose measured by glucometer stood at 183.5 mg/dL at the start, within the planned pre-race target, then fell to 119.5 mg/dL at 10 km, rose to 142.5 mg/dL at 19 km, dipped to 121.5 mg/dL at 30 km and finished at 108.5 mg/dL. These values remained within or close to a safe range throughout, showing that the pre-race insulin reductions and steady carbohydrate intake kept the runners’ blood sugar from collapsing under the metabolic demands of the distance. Only two hypoglycaemic measurements occurred, and both were in the same participant, who nevertheless completed the race. Notably, that runner had started with a glucose level below 140 mg/dL, beneath the study’s recommended pre-race floor, and consumed 49.5 grams of carbohydrate per hour, slightly less than the group median.

But the study also delivered a caution about the very technology that made it possible. CGM accuracy deteriorated substantially during the marathon. The intermittently scanned system differed from glucometer measurements by an average of approximately 43 per cent, and the real-time system by approximately 37 per cent. Both sensors overestimated capillary glucose, by +32.2 mg/dL and +50.4 mg/dL respectively. This matters because a runner who trusts an inflated sensor reading may believe their glucose is safe when it is in fact falling toward hypoglycaemia. Sensor error during prolonged exercise is thought to arise from a combination of factors, including reduced subcutaneous blood flow as the body shunts blood to working muscle, sweat interfering with sensor adhesion, compression of the sensor site, and the lag between interstitial fluid glucose, which CGM devices measure, and blood glucose, which changes fastest during rapid metabolic swings.

The authors drew a practical conclusion from this discrepancy. In a statement, they said: In this small observational study, all runners with type 1 diabetes completed the marathon, with performance comparable to controls. The runner who experienced low blood sugar had started the race with a glucose level below 140 mg/dL. During the marathon, CGM readings differed from glucometer measurements. For longer endurance events, runners should therefore consider checking their glucose with a glucometer, especially when the sensor reading does not match how they feel. That advice effectively reframes CGM as a trend-monitoring tool rather than a standalone decision-making instrument during ultra-endurance efforts, with fingerstick confirmation reserved for moments when symptoms and sensor numbers diverge.

The research team emphasised that the findings should not be read as a green light for unsupervised endurance racing. They noted that fear of hypoglycaemia is the main barrier to physical activity and affects up to 45 per cent of people with type 1 diabetes despite the major health benefits of regular exercise, and that managing glucose is challenging when levels change rapidly and responses vary between individuals. Their message was nonetheless an optimistic one: with appropriate education and careful blood sugar management, people with type 1 diabetes can successfully take part in even very demanding endurance exercise. They advised anyone with type 1 diabetes preparing for a marathon to discuss an individual glucose, carbohydrate and hydration plan with their doctors before the event, stressing that the most important element is an appropriate insulin management strategy, including reductions in basal and prandial insulin, and that baseline glucose control, exercise experience, diabetes duration and complications all shape individual risk. Some people, they added, should consult a cardiologist before starting endurance training. The team, which supports many athletes with type 1 diabetes, including competitors at the Olympic Games, Ironman triathlon finishers and a runner who completed ten marathons in ten consecutive days, presents the study as further evidence that the condition need not disqualify anyone from the marathon start line, provided the science of glucose management is respected as rigorously as the training plan itself.

Subject of Research: Glucose management, carbohydrate intake and CGM accuracy in amateur marathon runners with type 1 diabetes during a real-world 42 km race

Article Title: Running marathons with type 1 diabetes can be safe, shows small study using continuous glucose monitoring devices

Article References: Running marathons with type 1 diabetes can be safe, shows small study using continuous glucose monitoring devices. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: type 1 diabetes, marathon, continuous glucose monitoring, hypoglycaemia, endurance exercise, insulin adjustment, carbohydrate intake, CGM accuracy, MARD, EASD, sports medicine, glucose management