Continuous Glucose Monitoring

A special issue of Biosensors (ISSN 2079-6374).

Deadline for manuscript submissions: closed (15 June 2018) | Viewed by 69003

Special Issue Editor

Commonwealth Building, Hammersmith Campus, Imperial College, Du Cane Road, London W12 0HS, UK
Interests: type 1 diabetes; diabetes technology; continuous glucose sensing

Special Issue Information

Dear Colleagues,

Continuous glucose monitoring technologies provide information on glucose concentrations, direction and rate of change of glucose, and enable the analysis of historical trends. Real-time devices include alerts and alarms for rapid changes in glucose and for concentrations outside of specified ranges.

Clinical data suggest that continuous glucose monitoring can improve overall glucose control, as measured by glycated haemoglobin, and can reduce the burden of extreme glucose values (hypo- and hyperglycaemia).

However, devices remain invasive, accessing the subcutaneous interstitial fluid with a needle-type sensor, and cost remains a barrier to wider adoption in healthcare systems. Methods to improve needle-type sensors and alternative sensor methodologies have the potential to improve accuracy and precision, reduce cost, and may be more acceptable to people with diabetes. Non-invasive optical technologies and transdermal methods have been explored.

In this Special Issue, we seek unique research and development efforts, exploring technologies for continuous glucose sensing and its application for people with diabetes.

Prof. Nicholas Oliver
Guest Editor

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Keywords

  • Glucose
  • Continuous glucose monitoring
  • Electrochemical
  • Optical
  • Spectroscopy
  • Iontophoresis
  • Wearable
  • Monitoring
  • Point of care
  • Diagnosis
  • Diabetes
  • Type 1 diabetes
  • Type 2 diabetes
  • Artificial Pancreas
  • Sensor
  • Accuracy
  • Precision
  • Subcutaneous
  • Non-invasive

Published Papers (9 papers)

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Research

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17 pages, 903 KiB  
Article
Differences Between Flash Glucose Monitor and Fingerprick Measurements
by Odd Martin Staal, Heidi Marie Umbach Hansen, Sverre Christian Christiansen, Anders Lyngvi Fougner, Sven Magnus Carlsen and Øyvind Stavdahl
Biosensors 2018, 8(4), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/bios8040093 - 17 Oct 2018
Cited by 21 | Viewed by 7217
Abstract
Freestyle Libre (FL) is a factory calibrated Flash Glucose Monitor (FGM). We investigated Mean Absolute Relative Difference (MARD) between Self Monitoring of Blood Glucose (SMBG) and FL measurements in the first day of sensor wear in 39 subjects with Type 1 diabetes. The [...] Read more.
Freestyle Libre (FL) is a factory calibrated Flash Glucose Monitor (FGM). We investigated Mean Absolute Relative Difference (MARD) between Self Monitoring of Blood Glucose (SMBG) and FL measurements in the first day of sensor wear in 39 subjects with Type 1 diabetes. The overall MARD was 12.3%, while the individual MARDs ranged from 4% to 25%. Five participants had a MARD ≥ 20%. We estimated bias and lag between the FL and SMBG measurements. The estimated biases range from −1.8 mmol / L to 1.4 mmol / L , and lags range from 2 min to 24 min . Bias is identified as a main cause of poor individual MARDs. The biases seem to persist in days 2–7 of sensor usage. All cases of MARD ≥ 20% in the first day are eliminated by bias correction, and overall MARD is reduced from 12.3% to 9.2%, indicating that adding support for voluntary user-supplied bias correction in the FL could improve its performance. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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23 pages, 1807 KiB  
Article
Limits to the Evaluation of the Accuracy of Continuous Glucose Monitoring Systems by Clinical Trials
by Patrick Schrangl, Florian Reiterer, Lutz Heinemann, Guido Freckmann and Luigi Del Re
Biosensors 2018, 8(2), 50; https://0-doi-org.brum.beds.ac.uk/10.3390/bios8020050 - 18 May 2018
Cited by 35 | Viewed by 6692
Abstract
Systems for continuous glucose monitoring (CGM) are evolving quickly, and the data obtained are expected to become the basis for clinical decisions for many patients with diabetes in the near future. However, this requires that their analytical accuracy is sufficient. This accuracy is [...] Read more.
Systems for continuous glucose monitoring (CGM) are evolving quickly, and the data obtained are expected to become the basis for clinical decisions for many patients with diabetes in the near future. However, this requires that their analytical accuracy is sufficient. This accuracy is usually determined with clinical studies by comparing the data obtained by the given CGM system with blood glucose (BG) point measurements made with a so-called reference method. The latter is assumed to indicate the correct value of the target quantity. Unfortunately, due to the nature of the clinical trials and the approach used, such a comparison is subject to several effects which may lead to misleading results. While some reasons for the differences between the values obtained with CGM and BG point measurements are relatively well-known (e.g., measurement in different body compartments), others related to the clinical study protocols are less visible, but also quite important. In this review, we present a general picture of the topic as well as tools which allow to correct or at least to estimate the uncertainty of measures of CGM system performance. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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11 pages, 993 KiB  
Article
Consistency of Continuous Ambulatory Interstitial Glucose Monitoring Sensors
by Pei T. Wu, David E. Segovia, Cathy C. Lee and Kim-Lien Nguyen
Biosensors 2018, 8(2), 49; https://0-doi-org.brum.beds.ac.uk/10.3390/bios8020049 - 16 May 2018
Cited by 3 | Viewed by 4704
Abstract
Aims: The abdominal region is the most common location for continuous glucose monitor (CGM) sensor insertion. However, a paucity of post-marketing data is available to demonstrate intra-individual consistency of CGM readings at different abdominal insertion sites. Methods: Healthy adults (fasting glucose (FG) < [...] Read more.
Aims: The abdominal region is the most common location for continuous glucose monitor (CGM) sensor insertion. However, a paucity of post-marketing data is available to demonstrate intra-individual consistency of CGM readings at different abdominal insertion sites. Methods: Healthy adults (fasting glucose (FG) < 5.5 mmol/L; BMI < 30 kg/m2) were recruited and a CGM sensor was placed on each side of the abdomen. Postprandial and continuous 48-h interstitial glucose levels were analyzed. Results: There was no significant difference in the 3-h postprandial glucose (PPG) level derived from the left versus right CGM, which remained non-significant after adjusting for waist circumference or FG. Among the glucose levels recorded over 48-h, values on the left site were greater in 3.6% of the data points (p < 0.05). After adjusting for waist circumference, only 0.5% of the glucose values remained significantly greater on the left (p < 0.05). When adjusted for FG, similar results were observed. For both PPG and 48-h readings, the mean absolute relative difference was not significant between the two abdominal sites. Conclusions: CGM-derived glucose measures were highly consistent between the left and right abdomen during both the postprandial and post-absorptive periods. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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8 pages, 925 KiB  
Article
Accuracy of Continuous Glucose Monitoring before, during, and after Aerobic and Anaerobic Exercise in Patients with Type 1 Diabetes Mellitus
by Lyvia Biagi, Arthur Bertachi, Carmen Quirós, Marga Giménez, Ignacio Conget, Jorge Bondia and Josep Vehí
Biosensors 2018, 8(1), 22; https://0-doi-org.brum.beds.ac.uk/10.3390/bios8010022 - 09 Mar 2018
Cited by 39 | Viewed by 8578
Abstract
Continuous glucose monitoring (CGM) plays an important role in treatment decisions for patients with type 1 diabetes under conventional or closed-loop therapy. Physical activity represents a great challenge for diabetes management as well as for CGM systems. In this work, the accuracy of [...] Read more.
Continuous glucose monitoring (CGM) plays an important role in treatment decisions for patients with type 1 diabetes under conventional or closed-loop therapy. Physical activity represents a great challenge for diabetes management as well as for CGM systems. In this work, the accuracy of CGM in the context of exercise is addressed. Six adults performed aerobic and anaerobic exercise sessions and used two Medtronic Paradigm Enlite-2 sensors under closed-loop therapy. CGM readings were compared with plasma glucose during different periods: one hour before exercise, during exercise, and four hours after the end of exercise. In aerobic sessions, the median absolute relative difference (MARD) increased from 9.5% before the beginning of exercise to 16.5% during exercise (p < 0.001), and then decreased to 9.3% in the first hour after the end of exercise (p < 0.001). For the anaerobic sessions, the MARD before exercise was 15.5% and increased without statistical significance to 16.8% during exercise realisation (p = 0.993), and then decreased to 12.7% in the first hour after the cessation of anaerobic activities (p = 0.095). Results indicate that CGM might present lower accuracy during aerobic exercise, but return to regular operation a few hours after exercise cessation. No significant impact for anaerobic exercise was found. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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10 pages, 2523 KiB  
Article
Glucose Sensing Using Capacitive Biosensor Based on Polyvinylidene Fluoride Thin Film
by Ambran Hartono, Edi Sanjaya and Ramli Ramli
Biosensors 2018, 8(1), 12; https://0-doi-org.brum.beds.ac.uk/10.3390/bios8010012 - 30 Jan 2018
Cited by 27 | Viewed by 8482
Abstract
A polyvinylidene fluoride (PVDF) film-based capacitive biosensor was developed for glucose sensing. This device consists of a PVDF film sandwiched between two electrodes. A capacitive biosensor measures the dielectric properties of the dielectric layers at the interface between the electrolyte and the electrode. [...] Read more.
A polyvinylidene fluoride (PVDF) film-based capacitive biosensor was developed for glucose sensing. This device consists of a PVDF film sandwiched between two electrodes. A capacitive biosensor measures the dielectric properties of the dielectric layers at the interface between the electrolyte and the electrode. A glucose oxidase (GOx) enzyme was immobilized onto the electrode to oxidize glucose. In practice, the biochemical reaction of glucose with the GOx enzyme generates free electron carriers. Consequently, the potential difference between the electrodes is increased, resulting in a measurable voltage output of the biosensor. The device was tested for various glucose concentrations in the range of 0.013 to 5.85 M, and various GOx enzyme concentrations between 4882.8 and 2.5 million units/L. We found that the sensor output increased with increasing glucose concentration up to 5.85 M. These results indicate that the PVDF film-based capacitive biosensors can be properly applied to glucose sensing and provide opportunities for the low-cost fabrication of glucose-based biosensors based on PVDF materials. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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13 pages, 4022 KiB  
Article
A Cuprous Oxide Thin Film Non-Enzymatic Glucose Sensor Using Differential Pulse Voltammetry and Other Voltammetry Methods and a Comparison to Different Thin Film Electrodes on the Detection of Glucose in an Alkaline Solution
by Yifan Dai, Alireza Molazemhosseini, Kevin Abbasi and Chung Chiun Liu
Biosensors 2018, 8(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/bios8010004 - 06 Jan 2018
Cited by 29 | Viewed by 8455
Abstract
A cuprous oxide (Cu2O) thin layer served as the base for a non-enzymatic glucose sensor in an alkaline medium, 0.1 NaOH solution, with a linear range of 50–200 mg/dL using differential pulse voltammetry (DPV) measurement. An X-ray photoelectron spectroscopy (XPS) study [...] Read more.
A cuprous oxide (Cu2O) thin layer served as the base for a non-enzymatic glucose sensor in an alkaline medium, 0.1 NaOH solution, with a linear range of 50–200 mg/dL using differential pulse voltammetry (DPV) measurement. An X-ray photoelectron spectroscopy (XPS) study confirmed the formation of the cuprous oxide layer on the thin gold film sensor prototype. Quantitative detection of glucose in both phosphate-buffered saline (PBS) and undiluted human serum was carried out. Neither ascorbic acid nor uric acid, even at a relatively high concentration level (100 mg/dL in serum), interfered with the glucose detection, demonstrating the excellent selectivity of this non-enzymatic cuprous oxide thin layer-based glucose sensor. Chronoamperometry and single potential amperometric voltammetry were used to verify the measurements obtained by DPV, and the positive results validated that the detection of glucose in a 0.1 M NaOH alkaline medium by DPV measurement was effective. Nickel, platinum, and copper are commonly used metals for non-enzymatic glucose detection. The performance of these metal-based sensors for glucose detection using DPV were also evaluated. The cuprous oxide (Cu2O) thin layer-based sensor showed the best sensitivity for glucose detection among the sensors evaluated. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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Review

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12 pages, 392 KiB  
Review
Continuous Glucose Monitoring and Exercise in Type 1 Diabetes: Past, Present and Future
by Shaelyn K. Houlder and Jane E. Yardley
Biosensors 2018, 8(3), 73; https://0-doi-org.brum.beds.ac.uk/10.3390/bios8030073 - 03 Aug 2018
Cited by 28 | Viewed by 8275
Abstract
Prior to the widespread use of continuous glucose monitoring (CGM), knowledge of the effects of exercise in type 1 diabetes (T1D) was limited to the exercise period, with few studies having the budget or capacity to monitor participants overnight. Recently, CGM has become [...] Read more.
Prior to the widespread use of continuous glucose monitoring (CGM), knowledge of the effects of exercise in type 1 diabetes (T1D) was limited to the exercise period, with few studies having the budget or capacity to monitor participants overnight. Recently, CGM has become a staple of many exercise studies, allowing researchers to observe the otherwise elusive late post-exercise period. We performed a strategic search using PubMed and Academic Search Complete. Studies were included if they involved adults with T1D performing exercise or physical activity, had a sample size greater than 5, and involved the use of CGM. Upon completion of the search protocol, 26 articles were reviewed for inclusion. While outcomes have been variable, CGM use in exercise studies has allowed the assessment of post-exercise (especially nocturnal) trends for different exercise modalities in individuals with T1D. Sensor accuracy is currently considered adequate for exercise, which has been crucial to developing closed-loop and artificial pancreas systems. Until these systems are perfected, CGM continues to provide information about late post-exercise responses, to assist T1D patients in managing their glucose, and to be useful as a tool for teaching individuals with T1D about exercise. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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17 pages, 3617 KiB  
Review
Calibration of Minimally Invasive Continuous Glucose Monitoring Sensors: State-of-The-Art and Current Perspectives
by Giada Acciaroli, Martina Vettoretti, Andrea Facchinetti and Giovanni Sparacino
Biosensors 2018, 8(1), 24; https://0-doi-org.brum.beds.ac.uk/10.3390/bios8010024 - 13 Mar 2018
Cited by 71 | Viewed by 11103
Abstract
Minimally invasive continuous glucose monitoring (CGM) sensors are wearable medical devices that provide real-time measurement of subcutaneous glucose concentration. This can be of great help in the daily management of diabetes. Most of the commercially available CGM devices have a wire-based sensor, usually [...] Read more.
Minimally invasive continuous glucose monitoring (CGM) sensors are wearable medical devices that provide real-time measurement of subcutaneous glucose concentration. This can be of great help in the daily management of diabetes. Most of the commercially available CGM devices have a wire-based sensor, usually placed in the subcutaneous tissue, which measures a “raw” current signal via a glucose-oxidase electrochemical reaction. This electrical signal needs to be translated in real-time to glucose concentration through a calibration process. For such a scope, the first commercialized CGM sensors implemented simple linear regression techniques to fit reference glucose concentration measurements periodically collected by fingerprick. On the one hand, these simple linear techniques required several calibrations per day, with the consequent patient’s discomfort. On the other, only a limited accuracy was achieved. This stimulated researchers to propose, over the last decade, more sophisticated algorithms to calibrate CGM sensors, resorting to suitable signal processing, modelling, and machine-learning techniques. This review paper will first contextualize and describe the calibration problem and its implementation in the first generation of CGM sensors, and then present the most recently-proposed calibration algorithms, with a perspective on how these new techniques can influence future CGM products in terms of accuracy improvement and calibration reduction. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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Other

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6 pages, 208 KiB  
Commentary
Continuous Glucose Monitoring in Resource-Constrained Settings for Hypoglycaemia Detection: Looking at the Problem from the Other Side of the Coin
by Rubao Bila, Rosauro Varo, Lola Madrid, Antonio Sitoe and Quique Bassat
Biosensors 2018, 8(2), 43; https://0-doi-org.brum.beds.ac.uk/10.3390/bios8020043 - 25 Apr 2018
Cited by 6 | Viewed by 4695
Abstract
The appearance, over a decade ago, of continuous glucose monitoring (CGM) devices has triggered a patient-centred revolution in the control and management of diabetes mellitus and other metabolic conditions, improving the patient’s glycaemic control and quality of life. Such devices, the use of [...] Read more.
The appearance, over a decade ago, of continuous glucose monitoring (CGM) devices has triggered a patient-centred revolution in the control and management of diabetes mellitus and other metabolic conditions, improving the patient’s glycaemic control and quality of life. Such devices, the use of which remains typically restricted to high-income countries on account of their elevated costs, at present show very limited implantation in resource-constrained settings, where many other urgent health priorities beyond diabetes prevention and management still need to be resolved. In this commentary, we argue that such devices could have an additional utility in low-income settings, whereby they could be selectively used among severely ill children admitted to hospital for closer monitoring of paediatric hypoglycaemia, a life-threatening condition often complicating severe cases of malaria, malnutrition, and other common paediatric conditions. Full article
(This article belongs to the Special Issue Continuous Glucose Monitoring)
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