Continuous Glucose Monitors

December 2, 2009

cgmIlena George

Faculty peer reviewed

Are continuous glucose monitors the answer for better glucose control in diabetes?

A poorly controlled type 2 diabetic who is non-compliant with his at-home glucose monitoring comes to Bellevue’s Adult Primary Care Clinic requesting a prescription for a needle-less glucose monitor…

Self-monitoring of glucose levels is a necessary evil of diabetes treatment. As the prospect of numerous needle-sticks each day in perpetuity is daunting to patients, researchers have been developing non- or minimally-invasive methods to measure blood sugar in hopes of relieving the discomfort associated with self-monitoring blood sugar. Many posit that non-invasive testing will increase compliance with self-monitoring and tighten patients’ glucose control.

Arguably the most well-studied of the many different strategies and technological developments addressing this issue is the continuous glucose monitor.  Several devices have received FDA approval and are available commercially, with the stipulation that they are only to be used in conjunction with traditional home blood testing monitors. While the hope remains that continuous glucose monitoring brings us one step closer to an artificial pancreas that can both measure glucose and administer appropriate amounts of insulin, for now these devices lack the accuracy necessary even to replace traditional methods of self-monitoring blood glucose.1, 2 However, when used as an adjunct to needle-stick glucose measurements, studies including the Juvenile Diabetes Research Foundation sensor study found significant reductions in glycosylated hemoglobin levels in patients who used the continuous glucose monitors consistently, frequently, and properly. Little to no improvement was seen in subjects who were non-adherent.2, 3 For physicians, careful patient selection is a key part in determining the efficacy of these devices.2

Additionally, patients using a continuous glucose monitor appropriately may be better equipped to avoid hypoglycemic events.3 Although the glucose values displayed by the monitor may not be strictly accurate, the device provides useful information on patients’ upward or downward trends. Combined with traditional needle-stick glucose values, patients can anticipate falling glucose levels before they reach the hypoglycemic range. The devices have alarms that can be set to alert the wearer when levels exceed or drop below user-specified limits.4 Another benefit is that the devices collect and store data, which can be downloaded by the physician and further examined.  This can also reveal a patient’s laxity in taking insulin. 2 However, the question remains as to the best way to process the large amounts of data amassed, aside from simply noting trends.1

Researchers have evaluated the efficacy of these devices most vigorously in type 1 diabetics and type 2 diabetics requiring insulin. There is, however, some evidence for benefit in type 2 patients who are not on insulin as well. Allen et al demonstrated that visualizing glucose levels dropping on the monitor post-exercise provides positive reinforcement for otherwise sedentary patients to improve their habits.5

Despite the potential benefits, the drawbacks to these devices are numerous. Negative qualities include the necessity for frequent calibration with needle-stick values1 and the discomfort they cause the wearer.4   The sometimes tenuous relationship between the interstitial fluid glucose levels measured by many current devices and actual blood glucose levels6 can be made worse by inflammation and immune reactions caused by long-term use of the device.1   The machines are costly, while reimbursements for patients (and physicians) are often limited.2 Finally, not all studies reported positive outcomes. Recently published results from the MITRE study in England, as well as the STAR-1 study (a multi-center trial in the United States), found no improvement in hemoglobin A1c over controls in the groups equipped with monitors. While the study size of the MITRE study was much greater than most with over 400 participants, the continuous monitoring devices chosen are now outdated models (GlucoWatch), which are prone to side effects, and the minimum amount of time required for wearing a monitor was only 4 days a month. 7

This field is rapidly changing and evolving, with many players making a significant impact. The first real-time monitor, GlucoWatch G2 Biographer, is no longer available commercially. Originally produced by Cygnus, which was acquired by insulin pump manufacturer Animus Corps, which then became part of Johnson & Johnson, this was the first real-time glucose monitor and provided measurements every 10 minutes for 13 hours.8

The following continuous glucose monitoring devices are FDA-approved for use as an adjunct to blood testing:

Medtronic Guardian REAL-Time Continuous Glucose Monitoring System
MiniMed Paradigm REAL-Time System
Dexcom STS-7
Abbott FreeStyle Navigator. 

The MiniMed Paradigm REAL-Time System is the first combination insulin pump and continuous monitor. The original continuous monitoring system, produced by MiniMed, was retrospective as opposed to real-time and was approved in 1999. Medtronic also produces the Guardian system; it acquired Minimed and still uses the name in branding products. The Dexcom STS-7 was approved in 2007 and records glucose values every 5 minutes for 7 days; it is the successor to the STS, which was approved in 2006 and measured values every 5 minutes for 72 hrs. The Abbott FreeStyle Navigator is the most recent addition to this armamentarium; it was approved in 2008 and provides continuous measurements for up to 5 days.8, 9 These monitors measure glucose concentrations in the interstitial fluid; this accounts for the lag time noted between the monitor readings and blood glucose levels. 6

The devices require subcutaneous implantation of a sensor, making them minimally invasive rather than non-invasive.   The sensor sends information to a transmitter outside the body. The transmitter  powers the sensor and in turn sends the information to a handheld device that both displays and stores the glucose level.6  Chemically the device works by introducing an enzyme to oxidize glucose in the subcutaneous fluid.  A reduction reaction occurs at a second electrode and a glucose value is determined by measuring the resulting current.10 A stable reference electrode is  necessary to provide the working electrode with a defined voltage; this electrode may be combined with the counter electrode.10 For a concise table comparing current devices, see Kondepati 2007.1

For patients, the insertion of the sensor is comparable to the insertion of an insulin pump catheter, with minimal discomfort.11 The sensor is placed in the skin of the abdomen and sends information to the handheld device, which can be clipped to a patient’s clothing. While wearing the glucose monitor, more needle-sticks than usual for a patient may be necessary to calibrate the sensor.11 For devices currently on the market, sensor life is 3, 5, or 7 days. 8 Finally, cost may be prohibitive for patients whose private insurer does not cover the device.   Medicare and some private insurance companies have begun to pay for continuous glucose monitoring, but it is not universally covered. 11 The hardware costs at minimum $800, and sensors cost from 35 to 60 dollars each. 8 Some patients, blogging about their experiences with continuous glucose monitors, have noted tighter glucose control and decreased hemoglobin A1c levels, and some report greater ease in partaking in favorite physical activities (mountain climbing, for instance). However the reluctance of private insurers to cover the device and its prohibitive cost remain real obstacles.12, 13

The devices listed here represent only a small subset of glucose monitoring technology in development. Tura14 divides the methods currently being investigated into three categories: optical, electric and other. Under the optical category are infrared spectroscopy, optical coherence tomography, Raman spectroscopy, polarization, and fluorescence. Electric includes impedance spectroscopy, electromagnetic sensing and reverse iontophoresis. Finally, the “other” category includes ultrasounds, fluid harvesting and thermal spectroscopy. While current technology holds promise, the future will almost undoubtedly foster a sea change in diabetes management.

Ms. George is a 3rd year medical student at NYU Medical Center.

Peer reviewed by Minisha Sood, M.D., NYU Division of Endocrinology

References
1. Kondepati VR, Heise HM. Recent progress in analytical instrumentation for glycemic control in diabetic and critically ill patients. Anal Bioanal Chem. 2007; 388(3):545-563.

2. Hirsch IB. Realistic expectations and practical use of continuous glucose monitoring for the endocrinologist. J Clin Endocrinol Metab. 2009;94(7):2232-8.

3. Tamborlane WV, Beck RW. Continuous glucose monitoring in type 1 diabetes mellitus. Lancet. 2009; 373(9677):1744-1746.

4. Tamborlane WV, Beck RW, Bode BW, et al. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med. 2008;359(14):1464-1476.

5. Allen NA, Fain JA, Braun B, Chipkin SR. Feasibility and acceptability of continuous glucose monitoring and accelerometer technology in exercising individuals with type 2 diabetes. J Clin Nurs. 2009;18(3):373-383.

6. Khalil OS. Non-invasive glucose measurement technologies: an update from 1999 to the dawn of the new millennium. Diabetes Technol Ther. 2004;6(5):660-697.

7. Newman SP, Cooke D, Casbard A, et al. A randomised controlled trial to compare minimally invasive glucose monitoring devices with conventional monitoring in the management of insulin-treated diabetes mellitus (MITRE). Health Technol Assess. 2009;13(28):1-216.

8. Compare continuous glucose monitors.DiabetesNet. http://www.diabetesnet.com/diabetes_technology/continuous_monitoring.php. Accessed August 24, 2009.

9. FDA recently approved devices page. Food and Drug Administration Web site. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/default.htm. Accessed August 24, 2009.

10. McGarraugh G. The chemistry of commercial continuous glucose monitors. Diabetes Technol Ther. 2009; 11 Suppl 1:S17-24.

11. Continuous glucose monitoring for diabetes. WebMD. http://diabetes.webmd.com/continuous-glucose-monitoring. Accessed September 12, 2009.

12. Wearing a continuous monitor-some observations. Mountains for Active Diabetics. http://diabetic.friendsinhighplaces.org/wearing-continuous-glucose-monitor-some-observations. Accessed September 12, 2009.

13. Continuous Glucose Monitoring 24×7. http://glucose24x7.blogspot.com/. Accessed September 16, 2009.

14. Tura A. Noninvasive glycaemia monitoring: background, traditional findings, and novelties in the recent clinical trials. Curr Opin Clin Nutr Metab Care. 2008;11(5):607-612.

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