Noninvasive Tests Could Ease Diagnosis and Monitoring in Diabetes

A recent report in the Journal of the American Medical Association, based on research from the CDC between 2011 and 2012, found that 16.9% of youth and 34.9% of adults in the United States are obese. Although the prevalence of obesity has not changed significantly in the past decade,¹ it remains a substantial burden on the healthcare system, as obese youth are more likely to present risk factors for cardiovascular disease and obese adolescents are more likely to develop prediabetes.²

Diabetes necessitates a constant monitoring of blood glucose levels, with finger pricks several times a day. This can be quite distressing, especially for younger patients. The thought of the associated pain and discomfort can interfere with self-testing and negatively impact disease management. With this in mind, several research groups have been actively seeking noninvasive methods to diagnose individuals with diabetes and to efficiently monitor blood glucose in diabetic patients.

Salivary Biomarkers

One study published recently in the journal PLOS One evaluated adipokines as salivary biomarkers for the diagnosis of type 2 diabetes mellitus (T2DM).³ Adipokines, secreted from white adipose tissue, have been implicated in obesity, T2DM, and cardiovascular disease.⁴ Of the 8319 Kuwaiti children (aged 10 to 12 years) whose saliva samples were collected for the experiment, expression levels of 20 hormones and cytokines were evaluated in a random cohort of 744 individuals. The study identified significant changes in 4 salivary biomarkers: insulin, C-reactive protein (CRP), adiponectin, and leptin, which were specifically upregulated in obese children. The authors conclude that an early diagnosis of these markers could help regulate metabolic diseases and evaluate prophylactic therapies in children.

A Salivary Glucometer?

The iQuickIt Saliva Analyzer, being developed by Quick, LLC, shows promise. The analysis requires placing a single-use Draw Wick in the patient’s mouth to obtain a sample of their saliva, and then placing it in the analyzer for testing. The data generated following the test can be stored, as well as shared, with a smart device.⁵

In addition to internal evaluation, Quick is launching a clinical study of an iQuickIt Saliva Analyzer prototype in conjunction with the institutional review board of a leading healthcare network, according to William A. Petit, MD, chief scientific officer. Petit informed Evidence-Based Diabetes Management that there is no current estimate of when the product will be commercially available.

Regarding the device’s accuracy, Petit said, “Once additional data from the clinical study are available in fall 2014, and following additional calibration of the product, we will be able to determine if occasional monitoring by other means will be recommended.” He added that the device will be priced competitively with currently available glucometers, and that the company does not foresee any significant obstacles to the product qualifying for equivalent insurance reimbursement.

Continuous Glucose Monitoring System

The emerging continuous glucose monitoring (CGM) systems are appealing in that they provide the user the ability to monitor his or her glucose levels in real time. Although the reviews from patients are mixed—some patients consider it an information overload that can cause anxiety, while others appreciate the ease of use, the ability to monitor hypoglycemia, and the relatively painless insertion⁶—the technology is definitely a step in the right direction. The Table lists some of the older devices available on the market, while the products described below are still under development:

Non-Invasive Device

Smart Lens

Novartis has followed Google’s precedent for out-of-the-box approaches, this time in healthcare. Following “Google Glass,” scientists at Google announced the development of an ocular monitoring device: the “smart lens.”⁷ Subsequently, in July of this year, the eye care division of Novartis, Alcon, announced its partnership with Google—a team within Google built to address global issues—to develop a lens that can address ocular conditions.⁸

In an e-mail response, Alcon representatives informed EBDM that the smart lens technology involves noninvasive sensors, microchips, and other miniaturized electronics embedded in the contact lenses. Alcon is currently focusing on utilizing the technology in 3 areas:

• Helping diabetic patients manage their disease by providing a continuous, minimally invasive measurement of the body’s glucose levels via a “smart contact lens” designed to measure tear fluid in the eye and connect wirelessly with a mobile device;

• For people living with presbyopia who can no longer read without glasses, the “smart lens” has the potential to help restore the eye’s natural autofocus on nearby objects in the form of an accommodative contact lens or intraocular lens as part of the refractive cataract treatment;

• In addition to patients living with presbyopia, the “smart lens” technology shows potential for addressing other critical eye health conditions, such as glaucoma.

Officials informed EBDM that exploratory clinical trials have been conducted by Google with regard to the glucosesensing lens prototype, and additional clinical studies will soon be initiated as part of Alcon’s development efforts. However, the product is in very early stages of development and may not on the market for some time.

Invasive Devices

FiberSense/EyeSense

A diagnostic devices company called EyeSense, based in The Netherlands, has developed CGM systems fabricated with fiber optic material, with labeled biological molecules that act as glucose sensors within a hydrogel matrix. The sensor can be implanted either under the skin or under the conjunctiva of the eye to measure glucose in the surrounding tissue fluid. The readings are monitored with a fluorescent photometer attached to the skin (for FiberSense) or a photometer that reads varying emission wavelengths from the sensor (EyeSense).⁹

Advantages of CGM

The CGM products under development could prove a definite advantage for all involved—the patient, of course; the physician; and the insurance companies covering treatment. From the patient’s perspective, CGM eliminates the need to remember to periodically test blood sugar levels, which could have a tremendous impact on quality of life.

The device ensures that even as the patient sleeps, glucose levels are under surveillance. Additionally, the data acquired by most of the CGM systems can be sent to a smart device, which can keep the patient’s provider updated in real time. The physician who cares for the patient can rest assured that the constant monitoring will prevent episodes of hyperglycemia or hypoglycemic shock. Hypoglycemia, a serious complication associated with diabetes treatment, leaves a significant mark on the healthcare system in the United States, as previously discussed in EBDM.¹⁰

Scientists in the field are evaluating

CGM as a method of diagnosing early dysglycemia (prediabetes), now recognized as a risk factor for diabetes. One such study, which used a CGM system to monitor first-degree relatives of diabetes patients who were obese but lacked symptoms of diabetes, recognized the presence of significant dysglycemia in these individuals.¹¹ As childhood obesity rapidly develops into a global epidemic, CGM systems can prove valuable in monitoring the younger high-risk population.

Disadvantages

As with many new technologies, these devices are a work in progress, and accuracy seems to be a major concern both for patients and for providers of care. Drawbacks of these devices include a high rate of false-positive alarms and a lack of success in detecting episodes of hypoglycemia.¹² One such device, Medtronic’s Minimed 530G with the Enlite sensor, was reviewed in EBDM by

diabetic patient Brian Hegarty. Hegarty wrote that the sensor is inaccurate and the system as a whole is not well synchronized.¹³

The need for finger pricking is reduced—not completely eliminated—with CGM systems. The device needs to be calibrated, which means resorting to the traditional method of measuring blood glucose. Additionally, when the device detects hyperglycemia or hypoglycemia, reconfirming blood glucose levels before taking corrective measures is necessary.¹⁴

Compared with a glucometer, the devices have a lag in their glucose reading; this is because of the different modus operandi. CGM systems detect glucose levels in the interstitial fluid rather than in the blood. This argues for using the devices to monitor the trend in blood glucose levels, rather than using them to measure the actual levels at a point in time.¹⁴ Overall, though, when combined with intermittent self-monitoring, CGM provides diabetic patients an improved handle on their disease.

Where Does Reimbursement Stand?

CGM does not come cheap—the systems costs over $1000, and the sensors need to be replaced every few days.¹⁵ The good news is that reimbursement woes are a thing of the past for these devices, at least on the commercial insurer front. Based on information on the websites of the major vendors Dexcom and Medtronic, most commercial health plans (including Aetna, UnitedHealthcare, Humana, Kaiser, Blue Cross Blue Shield, and Anthem) cover the cost of the currently marketed devices.^16,17

The uphill battle has been with Medicare. While the government insurer covers professional CGM, such as systems used in hospitals or clinics,¹⁵ the personal CGM system has not earned similar acceptance. This could mean a big transition for retirees who switch to Medicare from employer-based private insurance plans—an important topic of discussion on several diabetes forums.^18,19

Representative Carol Shea-Porter (D-NH) introduced a bill before the House Energy and Commerce Committee late last year to amend Medicare CGM coverage, which was subsequently referred to the Subcommittee on Health.²⁰ Additionally, organizations such as JDRF are spreading the word, asking people to support the bill.²¹ The wheels are in motion, and hopefully, a decision will soon be made.References

1. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014;311(8):806-814.

2. Childhood obesity facts. CDC website. http://www.cdc.gov/healthyyouth/obesity/facts.htm. Updated February 27, 2014. Accessed August 8, 2014.

3. Goodson JM, Kantarci A, Hartman M, et al. Metabolic disease risk in children by salivary biomarker analysis. PLoS One. 2014;9(6):e98799.

4. Kwon H, Pessin JE. Adipokines mediate inflammation and insulin resistance. Front Endocrinol (Lausanne). 2013;4(71). doi:10.3389/fendo.2013.00071.

5. iQuickIt website. http://www.iquickit.com/iquickit/. Accessed August 7, 2014.

6. Continuous glucose monitoring system (CGMS): new technology advances diabetes care. Columbia University Medical Center website. http://nbdc.cumc.columbia.edu/news/continuous-glucosemonitoring-system-cgms. Published April 29, 2014. Accessed August 11, 2014.

7. Womack, B. Google unveils smart contact lens project to monitor glucose. Bloomberg website. http://www.bloomberg.com/news/2014-01-17/google-unveils-smart-contact-lens-project-tomonitor-glucose.html. Published January 17, 2014. Accessed September 3, 2014.

8. Novartis to license Google “smart lens” technology [press release]. Basel, Switzerland: Novartis; July 15, 2014. http://www.novartis.com/newsroom/media-releases/en/2014/1824836.shtml.

9. EyeSense website. http://en.eyesense.com/product/. Accessed August 11, 2014.

10. Dangi-Garimella, S. The persistent complication of hypoglycemia in diabetics. Am J Manag Care. 2014;20(SP8):SP251-SP252.

11. DeVries JH. Continuous glucose monitoring: coming of age? Eur J Endocrinol. 2012;166(1):1-4.

12. Soliman A, DeSanctis V, Yassin M, Elalaily R, Eldarsy NE. Continuous glucose monitoring system and new era of early diagnosis of diabetes in high risk groups. Indian J Endocrinol Metab.

2014;18(3):274-282.

13. Hegarty B. My initial impression of Medtronic’s new pump. Am J Manag Care. 2014;20(SP4):SP119.

14. Medical devices: continuous glucose monitoring. Cleveland Clinic website. http://my.clevelandclinic.org/devices/glucose_monitoring/hic_continuous_glucose_monitoring.aspx. Accessed August 14, 2014.

15. Vashist SK. Continuous glucose monitoring systems: a review. Diagnostics. 2013;3:385-412.

16. Reimbursement. Dexcom website. http://www.dexcom.com/reimbursement. Accessed August 14, 2014.

17. CGM billing and reimbursement guide. Medtronic website. http://professional.medtronicdiabetes.com/docs/CGM-Billingand-Reimbursement-Guide.pdf. Published 2014. Accessed August 14, 2014.

18. Community: adults living with type 1. American Diabetes Association website. http://community.diabetes.org/t5/Adults-Living-with-Type-1/Lost-Appeal-to-Get-Continuous-Glucose-Monitor-Sensors-Paid-for/td-p/272390. Accessed August 22, 2014.

19. Keeping it real on Medtronic’s 530G. http://www.diabetesmine.com/2013/10/keeping-it-realon-medtronics-530g.html. Published October 8, 2013. Accessed August 15, 2014.

20. H.R.3710 - Medicare CGM Coverage Act. https://beta.congress.gov/bill/113th-congress/house-bill/3710. Congress.gov website. Accessed August 14, 2014.

21. CGM coverage by Medicare. http://advocacy.jdrf.org/our-work/medicarecovercgm/. Accessed August 14, 2014.