Abbott Laboratories' FreeStyle Libre CGM. The sensor and transmitter are fixed to the upper arm and the receiver shows current blood glucose level and a graph of recent blood glucose levels.
A continuous glucose monitor (CGM) is a device used for monitoring blood glucose on a continual basis instead of monitoring glucose levels periodically by drawing a drop of blood from a finger. This is known as continuous glucose monitoring. CGMs are used by people who treat their diabetes with insulin, for example people with type 1 diabetes, type 2 diabetes, or other types of diabetes, such as gestational diabetes.
a transmitter that sends readings from the electrode to a receiver at regular intervals (every 1 to 15 minutes)
a separate receiver that shows the glucose level on a display.
Currently approved CGMs use an enzymatic technology which reacts with glucose molecules in the body's interstitial fluid to generate an electric current that is proportional to glucose concentration. Data about glucose concentration is then relayed from a transmitter attached to the sensor to a receiver and display that shows the data to the user.[1]
Some CGM devices must be calibrated periodically with traditional blood glucose measurements,[2] but others do not require calibration by the user.[3]
Benefits
Continuous glucose monitoring is gaining in popularity for a variety of reasons.
Traditional fingerstick testing measures blood glucose levels at only a single point in time. CGM enables users to see blood glucose levels continually, as well as trends in blood glucose levels over time.
CGM is more convenient and less painful than traditional fingerstick testing.
Some studies have demonstrated that CGM users spend less time in hypoglycemia or with lower glycated hemoglobin, both of which are favorable outcomes.[1]
Continuous glucose monitors appear to lower hemoglobin A1c levels more than just monitoring with capillary blood testing, particularly when CGM is used by people with poorly controlled diabetes and combined with the use of an integrated insulin pump.[4] However, a Cochranesystematic review found limited and conflicting evidence of the effectiveness of continuous glucose monitoring systems in children, adults, and users with poorly controlled diabetes.[4]
Limitations
Continuous glucose monitoring has some important limitations:
CGM systems are not sufficiently accurate for detecting hypoglycemia, a common side-effect of diabetes treatment.[5] This is especially problematic because some devices have alarm functions to warn users about a hypoglycemic condition, and people might rely on those alarms. However, the Cochranesystematic review showed that the use of continuous glucose monitors did not increase the risk of hypoglycemia or ketoacidosis.[4] Some manufacturers warn users about relying solely on CGM-measurements. The National Institute for Health and Care Excellence recommends validating hypoglycaemic values with fingerprick testing.[6]
Another limitation of CGM is that glucose levels are taken from the body's interstitial fluid rather than from the blood. Because it takes time for glucose to travel from the bloodstream into the interstitial fluid, there is an inherent lag between actual blood glucose level and the level measured by the CGM. This lag time varies by both user and device, but it is usually 5 to 20 minutes.[7]
Flash glucose monitoring
The original Freestyle Libre monitor introduced by Abbott Diabetes Care in 2015 was described as doing "flash glucose monitoring," with a disposable 14-day sensor probe under the skin (as with other CGM sensors), but factory-calibrated without requiring calibration against a fingerstick glucose test. The sensor measures the glucose level of interstitial fluids (as a proxy for blood sugar levels) continuously; up to eight hours of these readings, averaged over each 15-minute period, are stored in the sensor unit, unlike most other CGM systems, which use a wireless link (typically Bluetooth) to an external device for each reading. Data stored in the sensor are transmitted on demand to a "reader" held within a centimeter or two of the sensor unit, employing near-field communication (NFC) technology.[8][9] As only eight hours worth of data can be stored, downloads must not be spaced more than eight hours apart.
Differences in US insurance coverage favoring "flash glucose monitoring" over "continuous glucose monitoring" were an advantage to early adoption of Abbott's less expensive system. In the UK, flash glucose monitors and sensors are available to many patients without charge on the National Health Service (NHS).[9]
The later Freestyle Libre 2 version of Abbott's device uses different, incompatible, sensors. It can be programmed to transmit a low blood sugar (hypoglycemia) or high sugar warning via Bluetooth to a nearby device and, as of 2023, transmits glucose readings via Bluetooth on a 60-second basis effectively making a CGM and not a flash glucose monitor. The following Freestyle Libre 3 is smaller, and transmits its readings via Bluetooth,[10] as other meters do; it is not described as flash monitoring.
History
United States
The first CGM system was approved by the FDA in 1999. Continued development has extended the length of time sensors can be worn, options for receiving and reading data, and settings for alerting users of high and low glucose levels.
The first iteration of the MedtronicMiniMed took glucose readings every ten seconds with average readings reported every five minutes. Sensors could be worn for up to 72 hours.[11]
A second system, developed by Dexcom, was approved in 2006. The sensor was approved for use for up to 72 hours, and the receiver needed to be within five feet for transmission of data.
In 2008, the third model was approved, Abbott Laboratories' Freestyle Navigator. Sensors could be worn for up to five days.[11]
In 2012, Dexcom released a new device that allowed for the sensor to be worn for seven days and had a transmission distance of 20 feet. Dexcom later introduced an app allowing data from the sensor to be transmitted to an iPhone. This system was approved for pediatric use in 2015.[11]
In September 2017, the FDA approved the first CGM that does not require calibration with fingerstick measurement, the FreeStyle Libre. The Libre is considered a "flash monitoring" system (FGM), and thus not a true ("real-time") CGM system[dubious–discuss].[12] This device could be worn for up to ten days, but required 12 hours to start readings.[13] and was followed by an updated device that could be worn for up to 14 days, and needed only one hour to start a new sensor.[14][15][16] The FreeStyle Libre 2 was approved in Europe in October 2018, and enabled configuration of alerts when glucose is out of range.
In June 2018, the FDA approved the Eversense CGM system (manufactured by Senseonics Inc) for use in people 18 years of age and older with diabetes. This is the first FDA-approved CGM to include a fully implantable sensor to detect glucose, which can be worn for up to 90 days.[17][18] The Eversense XL, a 180-day version of the system, was approved in Europe in October 2017.[19]
China
China develops and produces CGM systems. The first CGM system to be approved for the European Union is manufactured by Medtrum Technologies. The sensor's intended use is up to 14 days and measures glucose levels every 2 minutes via a smartphone application.[20] Medtrum was founded in 2008 and is based in Shanghai, China.[citation needed]
At the end of 2017, Medtrum introduced the TouchCare A6 CGM (later A7 or Slim in some countries) which measures glucose levels in the interstitial fluid up to 14 days. The TouchCare system comes with mobile applications, including a remote view application.[21] The TouchCare system has glucose alerts and requires calibration every 24 hours.[22]
At the end of 2021 the Medtrum Nano was announced, a very slim device not requiring calibration, approved for up to 14 days use, with customizable glucose alerts.[23]
Medtrum makes both CGM and insulin pumps, both controlled by a single smartphone application which enables the user to monitor glucose levels and trigger insulin delivery in a closed-loop system.
United Kingdom
UK NICE guidelines introduced for the NHS in March 2022 in England and Wales advise that all Type 1 diabetic patients should be offered either flash glucose monitoring or CGM. People with Type 2 diabetes should be offered flash glucose monitoring or CGM if they use insulin twice daily or more, are otherwise advised to finger-prick eight times a day, have recurrent or severe hypoglycemia, have impaired hypoglycemia awareness, or cannot monitor their own blood sugar levels but they or a caretaker could use a scanning device. Details differ in Scotland and Northern Ireland.[24]
Device characteristics
Continuous versus flash monitoring[dubious–discuss]: Dexcom, Eversense and Libre 2 and 3 use continuous monitoring where information on the glucose levels are continuously updated. Continuous monitoring allows to set automatic alarms that are triggered when the glucose level goes out of pre-configured thresholds. In contrast, with flash monitoring such as the Freestyle Libre1, the glucose level is read automatically by the sensor; however, data is only transmitted to the user on user request. The glucose information stored on the sensor contains all the data since the previous read (up to 8 hours). FreeStyle Libre 2 allows configuration of alarms when glucose reaches a pre-determined level.
Implantable sensors: Since the electronics and battery require a relatively large package, most CGM sensors are worn over the skin with the actual sensing probe penetrating the skin. However the Eversense sensor is an actual implant, and receives its power wirelessly from a so-called transmitter worn above the skin. The "transmitter" receives data from the sensor every 5 minutes and forwards that data to a nearby device wirelessly. However unlike the Freestyle Libre, the implanted device is too small to have its own battery and memory, so that no glucose readings are generated during periods in which the transmitter is not being worn.[25] The transmitter must be removed at least once a day for recharging (10 minutes) and replacement of the adhesive.[citation needed]
Closed-loop system
The CGM is a key element in the development of a "closed-loop" system for the treatment of type I diabetes. A closed-loop system monitors blood glucose by CGM and sends data to an insulin pump for calculated delivery of insulin without user intervention.[11] A number of insulin pumps currently offer an "auto mode" however this is not yet a fully closed loop system. There are several implementations, including the artificial pancreas system[26] and the open sourceOpenAPS.[27]
Emerging CGM technologies
The continuous glucose monitoring space remains subject to extensive research and development in building lower cost, more accurate and more easy-to-use sensing solutions, some of which aim to be noninvasive.[28] A noninvasive CGM has been defined as a medical device that can measure glucose levels in the body without puncturing the skin, drawing blood or causing any pain.[28]
As of August 2023, besides Dexcom and Abbott Diabetes, no other manufacturer has attained a significant market share worldwide.[29] There have been regulatory approvals of noninvasive sensing systems in Europe,[30] though market adoption has been low, not affecting the Abbott-Dexcom dominance.
Emerging invasive CGM technologies
Multiple invasive CGM solutions have been under development since the early 2000s.[31]
Senseonics has commercialized its 180-day Eversense XL sensing systems in both the U.S. and European markets. In June 2023, it announced what it deemed favorable safety and accuracy data for its 365-day sensor, suggesting it may be commercializable in the future.[32]
A solution built by U.S. firm GlySens, aimed to remove the need for an external reader by creating a sensor that could be implanted under the skin, that directly transmitted glucose values to an external app. As of August 2023, this undertaking has stalled and the system has not been approved anywhere and the company is defunct.[33]
Another invasive CGM technology under development by Profusa Inc, based in Emeryville, California, builds on sensing research projects previously undertaken by the company under DARPA grants.[34] This technology is composed of a hydrogel microsensor that is placed under the skin subcutaneously in a non-surgical procedure. In a 2020 literature review several biomedical engineers supported Profusa’s claims that the non-surgical insertion procedure differentiates it favorably from Senseonics’ Eversense system,[35] as the latter requires a surgical procedure to insert and remove the sensor. The Profusa sensor allegedly also does not need to be removed because it overcomes the foreign body response. A reader is placed on the skin on top of where the sensor is, with the sensor transmitting a light signal to it. The sensor is claimed to last for three to six months. The is information then passed on to a smartphone where it can be tracked through an app.[36] As of August 2023, this sensor has not attained regulatory approval in any jurisdiction, though a similar Profusa system measuring oxygen levels under the skin, has CE certification in Europe.[37] Profusa has filed to go public via SPAC transaction.[38]
A similar approach was under development by another California-based company called Metronom Health.[39] This company has not released news releases, nor has any news covered any progress in terms of its research and development.
Yet another invasive approach is being developed by Belgium-based Indigo Diabetes. Indigo states that it is developing a CGM called a "continuous multi-metabolite monitoring system (CMM)". It is designed to provide people living with diabetes access to information on their glucose and other metabolite levels at any given time.[40] It has yet to attain regulatory approval.
Emerging noninvasive CGM technologies
The ease of use many CGM users expect would be provided by a safe and accurate noninvasive device has led to significant innovation and research.
Noninvasive approaches can be divided into interstitial fluid-based, radio frequency-based or breath-based. Interstitial fluid-analyzing sensors either use a device to analyze fluid on the skin or under the skin by sending infrared lasers to detect glucose levels in fluid. Radio frequency devices go through the skin and may derive glucose level information from blood directly.
Apple has reportedly been working on a noninvasive CGM that it seeks to integrate into its Apple Watch. In March 2023 it was reported to have established proof-of-concept of a noninvasive CGM.[41] Another company working on noninvasive CGM is Masimo, which sued Apple for patent infringement in this area in 2020.[42] Masimo has also filed new patents through its subsidiary Cercacor (pending as of September 2023) covering a joint continuous glucose monitoring and pump-closed loop delivery system.[43]
Samsung announced that it would be incorporating glucose monitoring with its smartwatch with a targeted release year of 2025. As of October 2023 the last update was in December 2022. It is not clear whether the watch will integrate readings from an external CGM such as Dexcom's or Abbott's, or work standalone.[44] The company in 2020 published literature regarding a non-invasive method it had developed with MIT scientists to engage in continuous glucose monitoring using spectroscopy.[45] The company has filed patents related to this technology.[46]
SugarBeat, built by Nemaura Medical, is a wireless non-invasive blood glucose monitoring system using a disposable skin patch. The patch connects to a rechargeable transmitter which detects blood sugar and transfers the data to a mobile app every five minutes. The patch can be used for 24 hours. Electronic currents are used to draw interstitial fluid to the surface to analyse the glucose level. SugarBeat has achieved regulatory approval in Saudi Arabia[47] and Europe,[48] though market penetration rates remain very low. The company declared US$503,906 in revenue for the fiscal year ending March 2022,[49] which compares to Dexcom's more than $3 billion.[50]As of August2023[update] it had submitted a US FDA premarket approval application for sugarBEAT.[51]
Another noninvasive system is built by US company Movano Health. It uses a small ring placed on the arm. Movano said in 2021 that it was building the smallest ever custom radio frequency (RF)-enabled sensor designed for simultaneous blood pressure and glucose monitoring.[52] Movano is listed as MOVE on NASDAQ. By August 2023 Movano had shifted to building sensor rings for other parameters, such as heart rate, blood oxygen levels, respiration rate, skin temperature variability, and menstrual symptom tracking.[53]
DiaMonTech AG is a Berlin, Germany-based privately-held company developing the D-Pocket,[54] a medical device that uses infrared laser technology to scan the tissue fluid in the skin and detect glucose molecules. Short pulses of infrared light are sent to the skin, which are absorbed by the glucose molecules. This generates heat waves that are detected using its patented IRE-PTD method.[55] The company claims a high selectivity of its method, results of a first study have been published in the Journal of Diabetes Science and Technology. [56]
The BioXensor developed by British company BioRX uses patented radio frequency technology, alongside a multiple sensor (also capturing blood oxygen levels, ECG, respiration rate, heart rate and body temperature) approach.[57] The company claims this enables the measurement of blood glucose levels every minute reliably, accurately, and non-invasively. BioXensor had not received regulatory approval as of June2023[update].
Haifa, Israel-based company HAGAR completed a study of its GWave non-invasive CGM, reporting high accuracy. This sensor uses radiofrequency waves to measure glucose levels in the blood.[58] The device had not received regulatory approval anywhere as of August 2023. One of the criticisms of radiofrequency technology as a way of measuring glucose is that studies in 2019 found that glucose can only be detected in the far infrared (nanometer wavelengths), rather than radiofrequencies even in the centimeter and millimeter wavelength range, putting into question the viability of radio frequencies for measuring glucose.[59]
Glucomodicum is based in Helsinki, Finland. Their attempted solution uses interstitial fluid to non-invasively measure glucose levels continuously. It does not have regulatory approval.[60]
KnowLabs is a Seattle, U.S-based company building a CGM called the Bio-RFID sensor, which works by sending radio waves through the skin to measure molecular signatures in the blood, which Know Labs' machine learning algorithms use to compute the user's blood sugar levels. The company reported that it had built a prototype, but had not attained regulatory approval as of August 2023.[61]
Spiden is a Swiss startup building a multi-biomarker and drug level monitoring noninvasive smartwatch wearable with continuous glucose monitoring capability as its first application. [62] It has so far not attained regulatory appro val as of October 2023. In January of 2024, Spiden declared it had developed a prototype, with a claimed MARD (Mean Absolute Relative Difference) value to a reference glucose measurement of approximately 9%. [63]
Occuity, a Reading, UK-based startup is taking a different approach to noninvasive glucose monitoring, by using the eye.[64] The company is developing the Occuity Indigo,[65] which will measure the change in refractive index of the eye to determine the concentration of glucose in the blood.[66]
Related Research Articles
An insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin therapy. The device configuration may vary depending on design. A traditional pump includes:
Blood glucose monitoring is the use of a glucose meter for testing the concentration of glucose in the blood (glycemia). Particularly important in diabetes management, a blood glucose test is typically performed by piercing the skin to draw blood, then applying the blood to a chemically active disposable 'test-strip'. The other main option is continuous glucose monitoring (CGM). Different manufacturers use different technology, but most systems measure an electrical characteristic and use this to determine the glucose level in the blood. Skin-prick methods measure capillary blood glucose, whereas CGM correlates interstitial fluid glucose level to blood glucose level. Measurements may occur after fasting or at random nonfasting intervals, each of which informs diagnosis or monitoring in different ways.
Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Green Oaks, Illinois, United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate known drugs; today, it sells medical devices, diagnostics, branded generic medicines and nutritional products. It split off its research-based pharmaceuticals business into AbbVie in 2013.
A glucose meter, also referred to as a "glucometer", is a medical device for determining the approximate concentration of glucose in the blood. It can also be a strip of glucose paper dipped into a substance and measured to the glucose chart. It is a key element of glucose testing, including home blood glucose monitoring (HBGM) performed by people with diabetes mellitus or hypoglycemia. A small drop of blood, obtained from slightly piercing a fingertip with a lancet, is placed on a disposable test strip that the meter reads and uses to calculate the blood glucose level. The meter then displays the level in units of mg/dL or mmol/L.
JDRF is a nonprofit 501(c)(3) organization that funds type 1 diabetes (T1D) research, provides a broad array of community and activist services to the T1D population and actively advocates for regulation favorable to medical research and approval of new and improved treatment modalities. It was initially founded as the JDF, the Juvenile Diabetes Foundation. It later changed its name to the Juvenile Diabetes Research Foundation and is now known as JDRF.
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Noninvasive glucose monitoring (NIGM) is the measurement of blood glucose levels, required by people with diabetes to prevent both chronic and acute complications from the disease, without drawing blood, puncturing the skin, or causing pain or trauma. The search for a successful technique began about 1975 and has continued to the present without a clinically or commercially viable product.
MiniMed Paradigm is a series of insulin pumps manufactured by Medtronic for patients with diabetes mellitus. The pump operates with a single AAA battery and uses a piston-plunger pump to infuse a programmed amount of insulin into the patient through a length of tubing. The Paradigm uses a one-way wireless radio frequency link to receive blood sugar measurements from select glucose meters. The Paradigm RT series adds the ability to receive data from a mated continuous blood-glucose monitor. Although the pump can use these measurements to assist in calculating a dose of insulin, no actual change in insulin delivery occurs without manual user-intervention.
DexCom, Inc. is a company that develops, manufactures, produces, and distributes continuous glucose monitoring (CGM) systems for diabetes management. It operates internationally with headquarters in San Diego, California, and has manufacturing facilities in Mesa, Arizona and Batu Kawan, Malaysia.
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In medicine, monitoring is the observation of a disease, condition or one or several medical parameters over time.
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Nightscout is a free and open-source project, and associated social movement, that enables accessing and working with continuous glucose monitor (CGM) data. Nightscout software aims to give users access to their real time blood sugar data by putting this data in the cloud. In addition to browser-based data visualization, Nightscout can also be used to review data from a phone or smartwatch, or to remotely monitor CGM data for individuals with type 1 diabetes. Associated with Nightscout software is a broader "CGM in the Cloud" social movement, supporting individuals seeking to access and use realtime CGM data through commercial and DIY approaches.
The Open Artificial Pancreas System (OpenAPS) project is a free and open-source project that aims to make basic artificial pancreas system (APS) technology available to everyone. The OpenAPS project was designed with the idea of quickly getting the APS technology to more people using a direct approach, rather than waiting for clinical trials to be completed and regulatory approval to be granted.
Nemaura Medical Inc. is a UK based Medical Technology company developing a wireless non-invasive blood glucose monitoring system called SugarBeAT.
References
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↑ Thomas Diaz AM, ed. (November 2017). "Continuous Glucose Monitoring". Hormone Health Network. Endocrine Society. Archived from the original on 22 December 2017. Retrieved 24 August 2018.
↑ US20230226331A1,Kiani, Massi Joe E.; Pauley, Kevin Hughes& Vo, Hung Theet al.,"Modular wearable device for patient monitoring and drug administration",issued 2023-07-20
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