bims-glumda Biomed News
on CGM data in management of diabetes
Issue of 2025–04–06
thirteen papers selected by
Mott Given
  1. Comparison of glucose fluctuation between metformin combined with acarbose or sitagliptin in Chinese patients with type 2 diabetes: A multicenter, randomized, active-controlled, open-label, parallel design clinical trial.
  2. The Use of Freestyle Libre Glucose Monitoring System and Diabetes Treatment Progression in Type 2 Diabetes Mellitus: A Retrospective Cohort Study in Saudi Arabia.
  3. Exploring usability metrics in continuous glucose monitoring systems: insights from the voice of people with diabetes in Italy.
  4. Parameters of glycemic variability in continuous glucose monitoring as predictors of diabetes: a prospective evaluation in a non-diabetic general population.
  5. Accuracy of a 15-day Factory-Calibrated Continuous Glucose Monitoring System With Improved Sensor Design.
  6. An overview of the freestyle libre monitoring system for individuals with type 1 and type 2 diabetes.
  7. Perception of hyper-/hypoglycemia and its related factors in type 2 diabetes: a continuous glucose monitoring-based prospective observational study.
  8. GLUCOSENS study protocol: a continuous glucose monitoring system compared to fingerstick glucose monitoring in surgical wards - a two-centre before-after clinical trial.
  9. Dynamic Relationships Among Continuous Glucose Metrics and Momentary Cognitive Performance in Diverse Adults With Type 1 Diabetes.
  10. Continuous Glucose Monitoring-Measured Glucose Levels During Oral Glucose Tolerance Testing in Pregnancy.
  11. Continuous glucose monitoring among nurse practitioners in primary care: Characteristics associated with prescribing and resources needed to support use.
  12. Towards equitable access of innovative technologies such as continuous glucose monitoring and artificial intelligence for diabetes management.
  13. Graphene-Based Glucose Sensors with an Attomolar Limit of Detection.
  1. Chin Med J (Engl). 2025 Apr 03.
    Comparison of glucose fluctuation between metformin combined with acarbose or sitagliptin in Chinese patients with type 2 diabetes: A multicenter, randomized, active-controlled, open-label, parallel design clinical trial.
    Xiaoling Cai, Suiyuan Hu, Chu Lin, Jing Wu, Junfen Wang, Zhufeng Wang, Xiaomei Zhang, Xirui Wang, Fengmei Xu, Ling Chen, Wenjia Yang, Lin Nie, Linong Ji.
       BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM).
    METHODS: In this multicenter, randomized, open-label, active-controlled study, we recruited patients with type 2 diabetes mellitus aged 18-65 years with body mass index (BMI) within 19-40 kg/m2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data.
    RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. TBR below target level <3.9 mmol/L (TBR3.9): Acarbose: 2.86 ± 6.98% vs. Sitagliptin: 3.89 ± 9.43%, P = 0.042; TBR3.0: Acarbose: 0.96 ± 4.41% vs. Sitagliptin: 1.64 ± 6.73%, P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs. Sitagliptin: 23.96 ± 5.19%, P <0.001. No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV.
    CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia.
    TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000039424.
    DOI:  https://doi.org/10.1097/CM9.0000000000003477
  2. Cureus. 2025 Feb;17(2): e79705
    The Use of Freestyle Libre Glucose Monitoring System and Diabetes Treatment Progression in Type 2 Diabetes Mellitus: A Retrospective Cohort Study in Saudi Arabia.
    Raed A Aljohani, Hanan N Altaib, Mostafa A Kofi.
      Background Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disease in Saudi Arabia, with a prevalence rate of approximately 25%. Traditional blood glucose monitoring methods, such as finger stick tests, provide limited insights into blood glucose measurements and fluctuations contributing to clinical inertia. The advent of continuous glucose monitoring (CGM) systems, such as the FreeStyle Libre glucose monitoring system, has transformed diabetes management by offering comprehensive exposure of glucose data to healthcare providers. Objective This study aims to evaluate the impact of the FreeStyle Libre glucose monitoring system on diabetes management intensification and treatment progression provided by healthcare specialists among T2DM patients in primary healthcare settings in Riyadh, Saudi Arabia. Methods An observational, retrospective, 24-week, two-arm study was conducted at Prince Sultan Military Medical City. The study involved 188 T2DM patients who were either using standard capillary glucose monitoring or transitioned to the FreeStyle Libre system, and it was based on clinical discretion rather than randomization. The primary outcomes were to evaluate the effect of FreeStyle Libre on treatment intensification provided by healthcare providers and changes in HbA1c levels. Data analysis included descriptive statistics and hypothesis testing using R software. Results Participants using the FreeStyle Libre glucose monitoring system experienced higher rates of medication intensification, and the use of insulin correction doses, and a significant reduction in median HbA1c levels was observed at three months (9.19% vs. 9.6%, p=0.047). However, at six months, the median HbA1c further reduced to 9.07%, though the difference between groups was not statistically significant. Despite these improvements, healthcare provider visits due to hyperglycemia were higher in the FreeStyle Libre group (p<0.001). There were no significant differences in hypoglycemia-related visits between the two groups (p=0.09). Conclusion The FreeStyle Libre glucose monitoring system was associated with increased treatment intensification and a significant reduction in HbA1c at three months compared to standard glucometers. However, by six months, the reduction in HbA1c was no longer statistically significant between groups. The increased healthcare provider visits in the FreeStyle Libre group may be attributed to heightened glucose monitoring awareness rather than the true worsening of hyperglycemia. While CGM offers advantages in diabetes management, its impact on long-term glycemic control remains uncertain. Further research is needed to confirm these findings, assess patient adherence, and evaluate the long-term effectiveness of continuous glucose monitoring in diabetes care.
    Keywords:  continuous glucose monitoring (cgm); dibetes mellitus; freestyle libre; treatment intensification; treatment progression
    DOI:  https://doi.org/10.7759/cureus.79705
  3. Front Clin Diabetes Healthc. 2025 ;6 1472471
    Exploring usability metrics in continuous glucose monitoring systems: insights from the voice of people with diabetes in Italy.
    Martina Manzoni, Davide Minotti, Giovanni Toletti, Andrea Boaretto.
       Introduction: Continuous Glucose Monitoring (CGM) systems are crucial in diabetes management, offering clinical and psychological benefits despite operational challenges. Usability assessment of real-time and intermittently-scanned CGM systems is a notable research gap. This study, in collaboration with diabetes patient associations, explores CGM usability from the perspective of Italian individuals with diabetes.
    Methods: A roundtable discussion with patient association representatives was conducted to discuss CGM usability, followed by a detailed online survey of 281 Italian patients on CGM usage, satisfaction, and feature preferences.
    Results: Findings show a significant positive impact on Quality of Life (87/100) and moderate usability (66/100). Core CGM functions are widely used, while data sharing with healthcare professionals is underutilized. The study offers diverse insights into CGM usability from both the roundtable and survey data.
    Conclusions: The study underscores the importance of CGM in diabetes management and highlights the need for continuous technological improvements. It emphasizes the role of patient associations in enhancing communication with manufacturers and CGM education. Effective collaboration between healthcare professionals and patients is vital for optimal CGM use, advocating for personalized care strategies tailored to individual patient needs.
    Keywords:  continuous glucose monitoring; diabetes management; healthcare technology; patient perspectives; patient-centered care; quality of life; usability indicators; user satisfaction
    DOI:  https://doi.org/10.3389/fcdhc.2025.1472471
  4. Adv Lab Med. 2025 Mar;6(1): 46-51
    Parameters of glycemic variability in continuous glucose monitoring as predictors of diabetes: a prospective evaluation in a non-diabetic general population.
    Javier Rodríguez García, Felix Camiña Darriba, Juan B Ortolá Devesa, Santiago Rodríguez-Segade Villamarín, Andrea Valle Rodríguez.
       Objectives: To prospectively examine the ability of some glycemic variability metrics from continuous glucose monitoring (CGM) to predict the development of diabetes in a non-diabetic population.
    Methods: A total of 497 non-diabetic patients from the AEGIS study were included. Participants used a CGM system (iPro2®) over a six-day period. The following parameters were analyzed: standard deviation (SD), coefficient of variation (CV) and mean amplitude of glucose excursion (MAGE). Six-years follow-up was performed. ROC curves were constructed to determine the predictive value of glycemic variability metrics. Sensitivity and specificity were calculated.
    Results: Of the 497 participants, 16 women (4.9 %) and 9 men (5.2 %) developed diabetes. Initial HbA1c and fasting glucose levels were significantly higher in the participants who ultimately developed diabetes. Glycemic variability metrics were also significantly higher in these subjects (SD: 18 vs. 13 mg/dL; CV: 17 vs. 14 %; MAGE: 36 vs. 27 mg/dL; p<0.001 in all cases). SD showed the highest AUC (0.81), with a sensitivity of 80 % and a specificity of 72 % for a cut-off of 14.9 mg/dL. AUCs were higher in men for all metrics.
    Conclusions: The metrics obtained by MCG, especially SD, are effective predictors of progression to type 2 diabetes in a non-diabetic population. These findings suggest that glycemic variability is useful for the early identification of subjects at a higher risk of developing diabetes.
    Keywords:  HbA1c; continuous glucose monitoring; diabetes; glycemic variability; mean amplitude of glucose excursions; standard deviation
    DOI:  https://doi.org/10.1515/almed-2025-0011
  5. J Diabetes Sci Technol. 2025 Apr 04. 19322968251329364
    Accuracy of a 15-day Factory-Calibrated Continuous Glucose Monitoring System With Improved Sensor Design.
    Shridhara Alva, Anuj Bhargava, Bruce Bode, Ronald Brazg, Kristin Castorino, Mark Kipnes, David R Liljenquist, Hien Tran, Hanqing Liu, Mohamed Nada.
       BACKGROUND: This study evaluates the performance of a 15-day factory-calibrated continuous glucose monitoring sensor used in FreeStyle Libre 2 Plus (Libre 2 Plus) and FreeStyle Libre 3 Plus (Libre 3 Plus) Systems, featuring an improved sensor design to reduce vitamin C interference.
    METHODS: Participants aged 2 years and above were enrolled for this study at seven sites in the United States. Depending on their age and bodyweight, participants attended up to three in-clinic sessions where venous blood was obtained for comparator measurement. For 2- to 5-year-olds, only capillary comparator data were collected. Participants aged 11 years and older underwent supervised glycemic manipulation to achieve glucose levels across the sensor's measurement range. Performance measures included the proportion of continuous glucose monitoring (CGM) values within ±20%/±20 mg/dL of comparator glucose values and mean absolute relative difference (MARD) between CGM and comparator values.
    RESULTS: Of the total 332 participants enrolled in the study, 149 adults and 124 pediatric participants (ages 6-17 years) had paired data for analysis against YSI comparator. Percentages within ±20 mg/dL/20% were 94.2% and 94.0%, and MARDs were 8.2% and 8.1% for the adults and pediatric participants, respectively. For 12 pediatric participants of 2 to 5 years, the percentage within ±20 mg/dL/20% was 86.6%, with an MARD of 11.2% against self-monitoring of blood glucose (SMBG) comparator. The sensor performed well in the hypoglycemic range, with 97.1% and 98.0% of results within ±15 mg/dL of the YSI comparator for the adult and pediatric participants, respectively.
    CONCLUSIONS: The Libre 2 Plus and Libre 3 Plus Systems provide accurate glucose results across the dynamic range during the 15-day sensor wear period.
    Keywords:  FreeStyle Libre 2; accuracy; continuous glucose monitoring; factory calibration; optional alarm
    DOI:  https://doi.org/10.1177/19322968251329364
  6. Expert Rev Med Devices. 2025 Apr 04.
    An overview of the freestyle libre monitoring system for individuals with type 1 and type 2 diabetes.
    Sergio Di Molfetta, Antonio Cutruzzolà, Agostino Gnasso, Concetta Irace.
       INTRODUCTION: Diabetes is a chronic disease with high prevalence, necessitating advanced technology to achieve glycemic targets and reduce complications. Continuous glucose monitoring (CGM) has become a cornerstone in diabetes management, with the Freestyle Libre (FSL) systems being some of the most widely used devices.
    AREAS COVERED: This review focuses on FSL systems, each including an all-in-one sensor and transmitter, a handheld reader and a Mobile Medical App (MMA). Glucose data are uploaded to a dedicated cloud-based platform for analysis. Over the years, FSL has evolved with new features offering valuable support for individuals with diabetes, caregivers, and healthcare providers. Clinical trials and real-world studies have demonstrated efficacy and safety across diverse populations, including individuals with type 1 and type 2 diabetes, adolescents, and pregnant women with diabetes.
    EXPERT OPINION: FSL is a user-friendly system that meets the needs of patients and health care providers. The MMA allows a review of glucose metrics and pattern identification, and supports educational strategies and patient-tailored treatment. Future advancements, including ketone monitoring, integration with wearable and other devices, and telemedicine applications, will further optimize diabetes care and prevention.
    Keywords:  Continuous glucose monitoring; FreeStyle Libre; flash glucose monitoring; type 1 diabetes; type 2 diabetes
    DOI:  https://doi.org/10.1080/17434440.2025.2489494
  7. Diabetol Int. 2025 Apr;16(2): 385-393
    Perception of hyper-/hypoglycemia and its related factors in type 2 diabetes: a continuous glucose monitoring-based prospective observational study.
    Yuka Suzuki, Aika Miya, Akinobu Nakamura, Takahisa Handa, Hiraku Kameda, Tatsuya Atsumi.
       Aims: Underestimating hyper-/hypoglycemia or failure to perceive hyperglycemia hinders optimal glucose management in diabetes care. Our study investigated individuals who, while aware of their hyper-/hypoglycemia, may not perceive them as problematic. Also, we clarified the factors contributing to discrepancies between these individuals' perceptions and the objective measurements.
    Materials and methods: This study was a prospective observational study comprising 284 Japanese individuals with type 2 diabetes who underwent ambulatory blinded professional continuous glucose monitoring (CGM) and self-administered the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Individuals with a time above range (TAR; > 180 mg/dL) ≥ 25% and those who answered 0 ("never") or + 1 ("almost never") for the frequency of hyperglycemia in the DTSQ were defined as having no-perception of hyperglycemia. Individuals with a time below range (TBR; < 70 mg/dL) ≥ 4% with an answer of 0 or + 1 for the frequency of hypoglycemia were labeled as having no-perception of hypoglycemia. Multivariate logistic regression analysis was performed to analyze clinical characteristics associated with the discrepancies between failure to perceive hyper-/hypoglycemia and TAR ≥ 25% or TBR ≥ 4%.
    Results: Insulin-use (odds ratio [OR] = 0.29, p < 0.05) and older age (OR = 1.05, p < 0.05) were independent determinants of no-perception of hyperglycemia. Low eGFR was an independent determinant of no-perception of hypoglycemia (OR = 0.94, p < 0.05).
    Conclusions: No-insulin-use, being an older adult, and renal dysfunction are linked to the discrepancy between the perception of hyper-/hypoglycemia and actual blood glucose. These results will help create personalized diabetes care.
    Keywords:  Continuous glucose monitoring; Hyperglycemia; Hypoglycemia; Perception; Type 2 diabetes
    DOI:  https://doi.org/10.1007/s13340-025-00803-3
  8. BMJ Open. 2025 Apr 02. 15(4): e095503
    GLUCOSENS study protocol: a continuous glucose monitoring system compared to fingerstick glucose monitoring in surgical wards - a two-centre before-after clinical trial.
    Helen Schultz, Marian Christin Petersen, Kasper Baasch Nielsen, Line Abrahamsen, Torill Donslund Nielsen, Ulla Linding Joergensen, Tine Lumbye Thomsen, Karoline Schousboe.
       INTRODUCTION: Effective glucose control in surgical patients at risk of hyperglycaemia and hypoglycaemia is crucial, as these conditions can lead to surgical site infections, prolonged hospital stays and death. Fingerstick glucose monitoring (FSGM), the standard measurement of glucose, can be painful for patients and time-consuming for nursing staff, especially with hourly monitoring around surgery. Continuous glucose monitoring systems (CGMS) offer a less invasive alternative with better glucose regulation in outpatients.The GLUCOSENS study compares the effects of CGMS and FSGM on point-of-care measurements and time-in-range (3.9-10.0 mmol/l) glucose levels (primary outcome), patient satisfaction and experience and nursing staff workload and experience in surgical wards. Furthermore, it evaluates CGMS accuracy during perioperative periods and medical imaging.
    METHODS AND ANALYSIS: This Danish two-centre study will be conducted at the general surgical wards of Odense and Zealand University Hospital and will involve 305 patients over 18 months. The study is divided into three periods: first, a standard care period with point-of-care FSGM (110 patients); second, an intervention period with point-of-care CGMS (110 patients); third, another standard care period with point-of-care FSGM combined with a blinded sensor for comparing continuous glucose data from this period with continuous glucose data from the intervention period (85 patients). Furthermore, the study will include 24 nursing staff.Data will be collected through medical file reviews on glucose levels, patient satisfaction questionnaires, a patient field study, an observation study of the nursing staff's workload and qualitative interviews of nursing staff.
    ETHICS AND DISSEMINATION: The study is registered with the Records of Processing Activities in the Region of Southern Denmark for research and quality projects (ID number: 23/36734) and has been approved by the Regional Scientific Ethical Committee in Southern Denmark (ID number: S-20240041). The results will be published in international peer-reviewed journals.
    TRAIL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06473480).
    Keywords:  Clinical Trial; DIABETES & ENDOCRINOLOGY; Nursing Care; Patient Satisfaction; SURGERY
    DOI:  https://doi.org/10.1136/bmjopen-2024-095503
  9. Diabetes Care. 2025 Mar 31. pii: dc242431. [Epub ahead of print]
    Dynamic Relationships Among Continuous Glucose Metrics and Momentary Cognitive Performance in Diverse Adults With Type 1 Diabetes.
    Claire J Hoogendoorn, Raymond Hernandez, Stefan Schneider, Anne Peters, Meredith Hawkins, Elizabeth A Pyatak, Jeffrey S Gonzalez.
       OBJECTIVE: Despite established relationships between glycemia and cognition, few studies have evaluated within-person changes over time. We paired continuous glucose monitoring (CGM) with ambulatory cognitive testing to examine bidirectional associations among adults with type 1 diabetes (T1D).
    RESEARCH DESIGN AND METHODS: Participants wore blinded CGM and completed ambulatory tests of perceptual speed and sustained attention five or six times daily for 14 days. CGM metrics were calculated over 3-h periods (mean glucose, %time in range [70-180 mg/dL], %time in low [<70 mg/dL], %time in high [181-250 mg/dL], %time in very high [>250 mg/dL], and coefficient of variation). Immediate glucose values within 15 min of cognitive assessments were also examined. Dynamic structural equation models evaluated bidirectional relationships over sequential 3-h periods.
    RESULTS: Among 182 diverse adults with T1D (age 40 ± 14 years, 46% male, 41% Latino, 29% White, 15% Black), more time in low glucose over 3 h was associated with slower perceptual speed at the end of that interval (P < 0.05) but not 3 h later. More time in high glucose (>250) was associated with faster perceptual speed initially but slower speed 3 h later (P < 0.05). Physical activity partially mediated the effect of high glucose on slower perceptual speed. Glycemia did not predict attention scores within persons. Lower attention and higher perceptual speed predicted higher mean glucose and more time in very high glucose over the following 3 h (P < 0.05).
    CONCLUSIONS: These novel observations of significant bidirectional association between glycemia and cognitive performance over the course of the day among adults with T1D emphasize the importance of examining within-person longitudinal effects over different time frames.
    DOI:  https://doi.org/10.2337/dc24-2431
  10. Diabetes Technol Ther. 2025 Apr 02.
    Continuous Glucose Monitoring-Measured Glucose Levels During Oral Glucose Tolerance Testing in Pregnancy.
    Anders L Carlson, Roy W Beck, Zoey Li, Elizabeth Norton, Richard M Bergenstal, Mary Johnson, Sean Dunnigan, Matthew Banfield, Katie Krumwiede, Judy Sibayan, Peter Calhoun, Celeste Durnwald.
      Background: To diagnose gestational diabetes mellitus (GDM), clinicians typically rely on the oral glucose tolerance test (OGTT). Continuous glucose monitoring (CGM) is a tool that could possibly be used to complement or replace the OGTT. Our aim is to describe CGM-derived glycemic patterns observed concurrently during the administration of a diagnostic OGTT in pregnancy. Methods: In total, 119 pregnant females underwent OGTT testing while wearing a blinded CGM sensor. Blood glucose (BG) measurements collected during the OGTT were compared with CGM-measured glucose values obtained using a Dexcom G6 Pro sensor to determine the differences between CGM-measured and BG levels during the OGTT, measure glycemic excursion during the OGTT, and determine differences in GDM diagnosis using standard BG draws during OGTT versus CGM-measured glucose levels. Results: CGM-measured glucose levels were on average higher than paired BG levels during the OGTT at each timed measurement (fasting, 1-, 2- and 3-h); fasting CGM-measured glucose levels in particular were higher than fasting BG levels by 6 ± 13 mg/dL. The median CGM minus BG-measured glycemic excursion during the OGTT was 12 and 4 mg/dL for the 75 g and 100 g OGTT, respectively. Of 28 participants diagnosed with GDM based on OGTT BG levels, 24 (86%) participants would have been diagnosed as GDM using CGM with BG-based thresholds; of 91 participants not diagnosed with GDM, 54 (59%) would also have not been diagnosed with GDM using CGM. Conclusions: CGM glucose measurements using Dexcom G6 Pro tended to be slightly higher than BG values during an OGTT, leading to more participants who would have been diagnosed with GDM if the BG-based OGTT thresholds were applied to these CGM-measured glucose values. When CGM is used for GDM diagnosis, diagnostic glucose criteria may need to be specific for the type of sensor used accounting for any bias in glucose measurement.
    Keywords:  OGTT testing; continuous glucose monitoring; gestational diabetes; pregnancy
    DOI:  https://doi.org/10.1089/dia.2024.0563
  11. J Am Assoc Nurse Pract. 2025 Apr 01. 37(4): 217-218
    Continuous glucose monitoring among nurse practitioners in primary care: Characteristics associated with prescribing and resources needed to support use.
      
    DOI:  https://doi.org/10.1097/JXX.0000000000001124
  12. Diabetes Res Clin Pract. 2025 Mar 30. pii: S0168-8227(25)00171-8. [Epub ahead of print]223 112157
    Towards equitable access of innovative technologies such as continuous glucose monitoring and artificial intelligence for diabetes management.
    Alicia J Jenkins, Noriko Kodani, Ranjit Mohan Anjana, Harish Ranjani, Elaine Chow, Young Min Cho, Ronald Ching Wan Ma.
      
    DOI:  https://doi.org/10.1016/j.diabres.2025.112157
  13. J Am Chem Soc. 2025 Apr 03.
    Graphene-Based Glucose Sensors with an Attomolar Limit of Detection.
    Vicente Lopes, Tiago Abreu, Mafalda Abrantes, Siva Sankar Nemala, Francesco De Boni, Mirko Prato, Pedro Alpuim, Andrea Capasso.
      Diabetes mellitus, a prevalent metabolic disorder affecting hundreds of millions of people worldwide, demands continuous glucose monitoring for effective management. Current blood glucose monitoring methods, such as commercial glucometers, are accurate but are often perceived as uncomfortable. Motivated by the need for noninvasive, ultrasensitive alternatives, our study presents electrolyte-gated graphene field-effect transistors functionalized with glucose oxidase. We developed an optimized fabrication process that integrates a 32-transistor matrix within a miniaturized 1000 μm2 footprint, ensuring high device uniformity while enabling detection in 40 μL analyte volume. A comprehensive suite of techniques─including Raman spectroscopy, X-ray photoelectron spectroscopy, and water contact angle measurements─reveals the stepwise evolution of graphene chemistry and surface properties leading to the controlled immobilization of glucose oxidase. Our findings demonstrate p-type doping and tensile strain in the graphene channel across the nanomolar-millimolar glucose concentration range. The enzyme-catalyzed oxidation of glucose produces hydrogen peroxide in close proximity to the graphene channel, inducing a systematic shift in the Dirac point voltage toward more positive values. Under these conditions, the biosensor achieves an attomolar limit of detection and a sensitivity of 10.6 mV/decade, outperforming previously reported glucose sensors. Selectivity tests against common interferents such as lactate and ascorbic acid, as well as validation in artificial and human tears, demonstrate its robustness for real-world applications. Altogether, these findings position the electrolyte-gated graphene field-effect transistor as a transformative, noninvasive glucose-sensing platform, paving the way for next-generation continuous monitoring devices, including wearable formats for real-time, user-friendly diabetes management.
    DOI:  https://doi.org/10.1021/jacs.5c03552
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