Non-invasive blood glucose testing: the horizon
Devices for non-invasive glucose monitoring are already in use and many others will reach the market in the next five years. Steve Chaplin here examines recent findings related to the new technologies.
A modestly-sized watch can now be used to monitor health and fitness or locate your position anywhere on the planet to within several metres. With such technology so accessible, why do we still expect people with diabetes to prick their finger every time they need to measure their blood glucose?
No-one pretends that frequent finger prick testing holds much appeal but there is surprisingly little objective evidence to show how acceptable it is.1 It has been suggested that it may not be troublesome, even to children,2 and careful technique can greatly reduce pain.3 But most people with diabetes who need to monitor their blood glucose have no reliable alternative. Their acceptance might be different if there was another way.
Glucose monitoring technology has been inching forward for many years but the revolution has arrived – it’s just had a slow start. Devices for non-invasive glucose monitoring (NIGM) are already in use and many others will reach the market in the next five years. ‘New and emerging non-invasive glucose monitoring technologies’, a report from the University of Birmingham’s Horizon Scanning Research & Intelligence Centre (HSRIC),4 is therefore well timed.
Continuous glucose monitoring (CGM) devices that provide real-time continuous monitoring via sensors placed under the skin are available now for some of the 23 000+ patients who use a pump (see www.diabetes.co.uk/cgm/continuous-glucosemonitoring.html). NICE recommends the MiniMed Paradigm Veo sensor-augmented pump for adults and children with type 1 diabetes who meet criteria for difficulty in controlling glucose levels and frequent severe hypoglycaemia.5–7
Unlike CGM, NIGM does not compromise the skin barrier but its appeal goes further: the devices under development offer the flexibility and adaptability that come with modern technology. They offer continuous or intermittent measurement and there is potential to measure or integrate with other parameters such as protein, lactate, BMI, exercise and diet. NIGM could significantly improve quality of life and the quality of diabetes management.
What’s out there
Finding relevant information is one of the problems with assessing new technologies. The HSRIC report’s authors4 searched for technologies that had been introduced in the last 12 months or were likely to be marketed within five years in technology databases, clinical trial registries and conference reports; they also reviewed manufacturers’ websites and searched Google, media and news outlets. When the results were reviewed by a panel of four health care professionals with expertise in diabetes care and another with two people with diabetes and two carers of children with diabetes, they were left with 40 devices.
This shortlist includes FreeStyle Libre Flash, which uses a very fine subcutaneous sensor, and EyeSense, which requires insertion beneath the conjunctiva. Strictly speaking, neither meets the criterion of being noninvasive. A 2016 launch was anticipated for two devices – SugarBEAT and EyeSense – but 2017 now seems likely; a further seven may be launched by 2020. Of the others, 17 are currently prototypes or developers are looking for a commercial partner. Products earlier in the development pipeline were not included in the report.
The 40 devices tackle the problem of glucose measurement in different ways. Twenty-four offer intermittent glucose measurement, of which 12 do so through the skin (finger, arm, hand and ear lobe), seven use saliva or breath, and five use tear fluid. The remainder offer continuous measurement via the skin (13) or tear fluid (3).
Intermittent NIGM means that users can measure glucose when they choose but, because the device is not permanently in place, they need to take some kind of action to carry out the measurement. Continuously measuring devices are left in place until they need calibrating or charging, providing readings 24 hours a day.
There is also a variety of technologies to do the measuring, including optical, transdermal, electrochemical and other techniques (Table 1). At present, little is known about their accuracy or whether one offers advantages over the others.
(click the table for full-size image)
Table 1. Measurement techniques and their application in non-invasive glucose monitoring devices. (Adapted from: Horizon Scanning Research & Intelligence Centre. ‘New and emerging non-invasive glucose monitoring technologies.’ Copyright © University of Birmingham. [www.hsric.nihr.ac.uk])4
The ways in which non-invasive monitoring has been implemented range from the straightforward to the realm of sci-fi. They include several devices that require nothing more than placing a finger on or in a sensor. GlucoWise (www.gluco-wise.com) is a U-shaped sensor that fits over the corner of the hand between thumb and forefinger. Analyte is a handheld device that is inserted into the ear, whereas GlucoTrack is clipped to the ear lobe. Two devices that measure acetone or glucose in breath are essentially the equivalent of the breathaliser, and several devices sample saliva with a lollipop or stick which is then inserted into a meter. One Look, which measures light refraction in the eye, looks like a mobile phone. Sensors may be strips or single-use pens to sample tears or iontophoretic patches that link to a separate analyser. One uses gel as an electrode, another is designed as a watch. Several devices link with a smartphone or PC, allowing the user (or health professional) to store data in the cloud.
Some solutions to the challenge of measuring glucose are very imaginative. Engineers at the University of California have designed a wearable sensor they call a temporary tattoo; the current version lasts a day. The NovioSense sensor, a 15mm long metal coil, is placed in the lower eyelid where its gel coating absorbs water and creates contact between the device and tears. Novartis Alcon is using Google’s smart lens technology to develop a contact lens sensor that connects wirelessly with a mobile device. The EyeSense sensor is inserted under the conjunctiva for up to one year; there, it reversibly interacts with glucose and emits a fluorescent signal that is read with a handheld meter.
What do potential users and health professionals think?
Of course, all of this inventiveness is of little value if users don’t like it. The HSRIC report’s panels of potential users and health professionals were asked (after being informed about the devices) what features they’d like to see in an NIGM device. Their responses (summarised in Table 2) provide useful feedback but the number of participants was small, the report does not indicate how many of each panel made the comments it cites, and it is uncertain how representative their views are. Of course, the current option of finger prick testing offers few of these desirable qualities.
Table 2. What makes a good non-invasive glucose monitoring device? Summary of the views of people with diabetes (n=2), carers (n=2) and health professionals (n=4)4
Some of the devices also fall short of these aspirations. A frequent reservation expressed by health professionals was that it’s too early to comment on some devices because development is not complete or evidence from clinical use is not available. Potential users expressed concern about possible harms from devices that use lasers as a light source for spectroscopy. Infrared technology of the kind now used for capillary testing has the appeal of ‘do-ability’ but accuracy may be affected by the patient’s hydration.
Devices that require up to 3 minutes to produce a reading were considered too slow and bulky meters too inconvenient compared with handheld devices. Inserting a device into the ear did not appeal to potential users and health professionals noted that, in children, ear wax would pose a challenge. Sensors attached to the ear and sampling saliva with a lollipop would not be discreet, and watches that would otherwise be appealing might have problems coping with sweat (associated with hypoglycaemia) and would not suit small children. Patches would need to be resilient to the effects of heat, cold and sweat. The SugarBEAT patch, which lasts for up to 24 hours, requires a single finger prick for calibration and a 30-minute warm-up period.
There were concerns about the accuracy of measuring glucose in saliva and tears, and how well those levels correlate with capillary blood glucose. Health professionals had reservations about anything involving contact with the eyes, even the Google smart lens, and potential users were not keen on a sub-conjunctival implant or leaving a metal coil beneath the eyelid – the latter would certainly not appeal to children.
The FreeStyle Libre Flash received high approval ratings. This may be because panel members were more familiar with it; user feedback was described as ‘excellent’ and it produces high-quality data. On the other hand, it requires calibration; it cannot be prescribed; it doesn’t have an automatic alarm and wouldn’t be suitable for people who are hypoglycaemia unaware; and it is not accepted by the DVLA because of the lag between blood and interstitial glucose measurements.
Health professionals liked the promise of the GlucoWise system for integrating multiple health parameters and its wireless connectivity. Potential users pointed out that the complementary data would have to be entered into the system manually and that would be an unwelcome additional task for the user. GlucoTrack, which uses an ear sensor, is already available in Europe and appears to be less expensive than GlucoWise, though it lacks that device’s connectivity. Saliva sampling was better received by health professionals than potential users – it could prove useful for near-patient testing – but both liked breath testing (if, users said, the device was small enough to be discreet).
One obstacle that will slow the uptake of NIGM is the inertia inherent in clinical practice. A lot of time and effort have been invested in training staff and encouraging people to use finger prick testing. From the provider’s perspective, it is inexpensive, capillary blood is a proven way to measure glucose, and the meters are reliable. It’s not perfect but most people use the technique effectively, however much they dislike it.
Adopting a new technology – or perhaps several if patients are to be offered a choice – will require additional investment in training and patient support on top of the (probably) higher cost of the devices. NICE estimated that the sensor-augmented insulin pump will cost £1700–3000 annually more than the pump alone but save £1500 per year by avoiding other costs through better glycaemic control.8 There is also the risk that NICE will take its time deciding whether NIGM devices are cost effective.
People with diabetes can look forward to a near-future when they will not need to use finger pricks to monitor their glucose. It will be several years until the market offers a choice of devices and there are still some hurdles for NIGM to overcome.
From the health provider’s perspective, it’s likely that accuracy, reliability and cost will be paramount; when NICE comes to appraise the technology, much will depend on the negative impact of finger pricking on quality of life. Conversely, non-invasive testing could improve adherence to self-monitoring and, if these devices can be shown to improve glycaemic control, their future will be assured.
The technology behind NIGM devices is interesting but the comments noted in this HSRIC report4 suggest that users are primarily concerned with safety and the practicalities of use – convenience, appearance, connectivity – rather than the engineering. Even the most advanced gadget will fail if it does not offer a meaningful step forward for users.
1. Ong WM, et al. Barriers and facilitators to self-monitoring of blood glucose in people with type 2 diabetes using insulin: a qualitative study. Patient Prefer Adherence 2014;8:237–46.
2. Karges B, et al. Low discomfort and pain associated with intensified insulin therapy in children and adolescents. Diabetes Res Clin Pract 2008;80:96–101.
3. Nakayama T, et al. Painless self-monitoring of blood glucose at finger sites. Exp Clin Endocrinol Diabetes 2008;116:193–7.
4. Horizon Scanning Research & Intelligence Centre. New and emerging non-invasive glucose monitoring technologies. University of Birmingham, May 2016. (www.hsric.nihr.ac.uk).
5. National Institute for Health and Care Excellence. Integrated sensor-augmented pump therapy systems for managing blood glucose levels in type 1 diabetes (the MiniMed Paradigm Veo system and the Vibe and G4 PLATINUM CGM system). NICE Diagnostics Guidance DG21. NICE, February 2016.
6. National Institute for Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. NICE Guideline NG17. NICE, August 2015.
7. National Institute for Health and Care Excellence. Diabetes (type 1 and type 2) in children and young people: diagnosis and management. NICE Guideline NG18. NICE, August 2015.
8. National Institute for Health and Care Excellence. Resource impact report: Integrated sensor-augmented pump therapy systems for managing blood glucose levels in type 1 diabetes (the MiniMed Paradigm Veo system and the Vibe and G4 PLATINUM CGM system). (DG21). NICE, February 2016.