Large clinical trials have confirmed the benefits of good glycemic control. The Diabetes Control and Complications Trial (DCCT) showed a reduction in retinopathy, neuropathy, and microalbuminuria in type 1 patients treated with intensive insulin therapy (three or more injections a day or insulin pump therapy).1 The United Kingdom Prospective Diabetes Study (UKPDS) showed a reduction in microvascular and neuropathic complications with intense therapy in patients with type 2 diabetes.2 Despite all the evidence for good glycemic control, only about half of adult patients with diabetes have a glycosylated hemoglobin (A1C) less than 7%.3 The risk of hypoglycemia increases with insulin therapy; therefore, hypoglycemia can be a barrier to obtaining good glycemic control.
Self-Monitoring Blood Glucose
The first patent for a blood glucose meter was issued in 1971. In 1986, the American Diabetes Association (ADA), the CDC, the FDA, and the National Institutes of Health (NIH) recognized self-monitoring blood glucose (SMBG) as an important tool for effective management of diabetes.4 Before blood glucose meters, patients checked glucose concentrations in the urine to monitor their diabetes. Adjustment of medications was based on this inaccurate estimation. For patients on insulin therapy, documentation shows that SMBG improves glycemic control.5 A literature review showed an average reduction in A1C of 0.4% in patients with type 2 diabetes not on insulin therapy who performed SMBG.6 To date, there are no large randomized clinical trials that have examined the long-term effects of SMBG on patient satisfaction, hypoglycemic episodes, or glycemic control in patients not on insulin therapy. A review article concluded that use of SMBG in type 2 diabetes was an important factor in improving glycemic control.7
Currently, the ADA recommends that patients check SMBG three or more times a day if on multiple insulin injections or insulin pump therapy.5 The ADA does not provide specific guidelines for SMBG in patients using insulin less frequently or on noninsulin regimens. However, the ADA does recognize the utility of SMBG in preventing hypoglycemia, adjusting medication, and assessing diet and exercise.5 The significance of postprandial glucose levels remains controversial in the literature, but a recent study concluded that treating both fasting and postprandial glucose levels may improve long-term outcomes in patients with diabetes.8 Unfortunately, SMBG does not detect glycemic fluctuations or reflect the duration of glycemic excursions. SMBG shows only a snapshot of the blood glucose levels. Another limitation of SMBG is poor patient compliance, especially in adolescents with type 1.9
What Is Continuous Glucose Monitoring?
Continuous glucose monitoring (CGM) devices measure the glucose concentration of the interstitial fluid and have been commercially available since 1999.10 Earlier devices were blinded to the patient and provided data only at the time of download. The three newest generations of CGM devices are not blinded to the patient and provide real-time data. This article will focus on the latest generation of CGM devices, including the FreeStyle Navigator, DexCom SEVEN, and MiniMed REAL-Time and iPro systems. Real time simply means that patients are able to view their current values on an insulin pump or a receiver. The patient can view arrows and/or graphs that indicate where the glucose is trending. Unlike SMBG, which provides a number, patients are able to obtain information regarding the direction and rate at which the glucose levels are moving.10
These devices measure glucose levels every 1 or 5 minutes, and usually there is a close approximation between interstitial and blood glucose levels. However, interstitial levels may lag behind blood glucose by 5 to 20 minutes.10,11 This lag time is more pronounced (20 minutes) during times of rapid changes in glucose levels such as after a meal or a dose of insulin.10 Because of the potential lag time, patients must confirm with a standard blood glucose check before taking action. Current CGM systems are FDA indicated to use with traditional blood glucose testing, so it is important that patients realize CGM does not replace fingerstick blood glucose measurement.
Most devices consist of four components: an inserter, a sensor, a transmitter, and a display unit (receiver). The inserter implants the tiny sensor filament in the skin subcutaneously. Appropriate sites include the abdomen, legs, and arms. Basically, sensor sites are the same areas recommended for insulin pumps and manual insulin injections. Sensor sites should be 2 inches away from the navel or pump sites and 3 inches away from any manual injection site. Once the sensor is inserted at the appropriate site, the needle is removed. The sensor is disposable and can be worn for 3 to 7 days depending on the brand.11
The transmitter is connected to the sensor and detects the electrical signal generated by the oxidation of glucose in the interstitial fluid.12-15 This information is then sent from the transmitter to the display unit (insulin pump or a pager-size receiver). The transmitter is rechargeable and should be fully charged before using. An adhesive patch is used to secure the transmitter and reduce the risk of its getting caught on clothing. The transmitter is water resistant and does not require removal for bathing, swimming, or exercising. Communication from the transmitter to the receiver occurs by radio frequency signals from ranges up to 5 to 10 feet depending on the unit.12-14
The receiver displays a continuous picture of glucose levels. Patients are able to see their current glucose reading on the receiver. All systems allow a review of glucose values, in graph form, of the past 1, 3, 9, or 24 hours.12,13 Currently, only one company offers CGM data displayed on an insulin pump, while the others require a separate receiver.13 When linked to the insulin pump, patients may view current, real-time blood glucose readings and trend graphs on the pump screen. Another brand of CGM offers a blood glucose meter built into the receiver.14 In the future, more insulin pumps will have CGM capabilities.
All available systems offer the flexibility to set low and high alarms. These alarms alert the user by beeping or vibrating when the glucose value falls below or above a set threshold. For example, a patient with a history of hypoglycemia unawareness may set the low alarm at 80 mg/dL to enhance recognition. Patients should never rely solely on the alarms to enhance glycemic control.
Calibration
Patients wearing a real-time monitoring device must calibrate the sensor readings to a fingerstick blood glucose. The best time for calibration is when the blood glucose is not changing (i.e., is not fluctuating or is most stable), such as when fasting or before meals.11 Prior to calibration, patients should make sure their hands are clean and dry, check meter strips for the correct code and expiration date, and not use alternate site testing. Recommendations for calibration vary with each model, but most systems require one to three calibrations a day.
The initial training for CGM takes about 1 to 2 hours and can be conducted in a group setting or individually. There is a learning curve, and most patients start out with no alarms to get familiar with the system. After 3 to 5 days, the alarms for hypoglycemia and hyperglycemia can be turned on. A 1-week follow-up appointment is recommended to review the first week of data. Phone or face-to-face contact is recommended during the next 2 to 4 weeks.11 Patients must be trained to focus less on the actual blood glucose and instead to look at the trends. The use of CGM readings is an adjunct to SMBG, and patients must verify blood glucose concentrations with a fingerstick before making a treatment decision.
Uses of CGM
CGM can be used for personal or diagnostic purposes. Personal use of CGM would be by those patients who decide to purchase their own system. Diagnostic use is when an office owns the system. For diagnostic purposes, the CGM device can be placed on a patient during an office visit. Depending on which device is used, the patient may or may not be able to see the data. Patients are asked to keep a log of meals, blood glucose readings, medications, and exercise. After 3 to 7 days, the patient returns to clinic, the device is removed, and the data downloaded. Personal and diagnostic CGM can identify undetected nocturnal hypoglycemia, episodes of hypoglycemia unawareness, and excessive elevations in postprandial glucose (FIGURE 1).10,11 Often, nocturnal hypoglycemia goes undetected with standard SMBG. Potential therapy changes include adjustment of oral antihyperglycemic agents and/or insulin therapy. In addition, patients are able to see how food and exercise influence their glycemic control.
Some believe that patients need to be motivated, but one study concluded that patients with a higher A1C had the most improvement from wearing a CGM.16 Patients with type 2 diabetes who wear the sensor intermittently are able to identify changes in therapy or the effects of food and exercise on glycemic control.11 Patients who are good candidates for CGM are listed in TABLE 1.
Advantages of CGM
More frequent blood glucose monitoring increases the potential for detecting hyperglycemia and hypoglycemia. One negative effect of hypoglycemia is unconsciousness, which increases in children and adolescents with type 1 on intensive insulin therapy.15 Memory impairment and alterations in cognitive function are documented in children with type 1 diabetes and severe hypoglycemia.15 The CGM devices signal users when readings are high or low, which can help prevent significant hypoglycemic events or allow the patient to take additional action to lower elevated blood glucose readings. The fear of hypoglycemia may prevent patients from achieving optimal glucose control. The alarms for hypoglycemia may be of particular benefit to those patients with nocturnal hypoglycemia or hypoglycemia unawareness.11
One study enrolled 91 insulin-requiring patients (type 1, 75; type 2, 16).17 Patients were randomized to a control group (blinded to their glucose values) and a display group. The display group spent 26% more time in target range (80-140 mg/dL), 21% less time in the hypoglycemic range (<55 mg/dL), and 23% less time in the hyperglycemic (>240 mg/dL) range. Improvements occurred within 6 days of using a CGM device.17 Patients were able to manage episodes of hypoglycemia and hyperglycemia more effectively when they had access to their data.
A study of 367 patients with type 2 diabetes on multiple daily insulin therapy documented twice the number of hypoglycemic episodes with CGM. The study concluded that hypoglycemia is underreported with SMBG. This study also revealed postprandial elevations in patients with low A1C levels.18
A third study looked at elderly patients (>65 years old) with type 2 diabetes, an A1C of less than 7.5%, and on oral hypoglycemic therapy including a sulfonylurea. This study documented that hypoglycemia and excessive postprandial elevations were common in this patient population.19
Barriers for Use
Some disadvantages of CGM include cost, information overload for both providers and patients, inadequate time and reimbursement for diabetes education, and the potential for excessive intervention.10,11 If not covered by insurance, the initial cost to the patient can range from $400 to $2,000.20 Disposable sensors, which are changed every 3 to 7 days, can add to the monthly cost of supplies and medications. Reimbursement to patients purchasing their own systems continues to improve since CGM was first introduced. Initial and ongoing cost can be an obstacle for some patients.
Providers must have time to interpret the data. All systems provide software to patients and providers to download data. The MiniMed REAL-Time system allows providers to access the data (via the Internet) after the patient has downloaded from home.13 The other two systems (DexCom SEVEN and FreeStyle Navigator) allow patients to download at home where they can print out the data or e-mail it to their providers.12,14 Internet and e-mail access to data allows providers to review the data prior to appointments or as their schedule permits.
One disadvantage to the alarms is a potential for overcorrection.11 For example, if a patient continues to see a trend of hyperglycemia after a meal bolus, he or she may rebolus and increase the risk of hypoglycemia. In contrast, if the blood glucose is low and the patient eats and there is not an immediate rise in the levels, the patient may continue to treat, with hyperglycemia as the end result. There is a risk of insulin or food stacking if patients do not give sufficient time for the desired result. Patients must be educated about the kinetics of insulin and guided on interpreting alarms and trend arrows.
Benefits in Pregnancy
It is well documented that hyperglycemia in pregnancy correlates with large size for gestational age infants. A study in the British Medical Journal showed that infants of mothers using CGM had a lower birth weight and were at less risk for macrosomia than mothers not using CGM.21 In gestational diabetes, CGM may be very helpful in identifying those patients who need medical intervention, since SMBG may not reflect the true postprandial elevations.22 The use of CGM in type 1 patients can help fine-tune regimens and improve glycemic control prior to conception.22
Guidelines
Recommendations from diabetes organizations focus on the use of CGM in patients with type 1 diabetes. The ADA recognizes CGM as a useful tool for adults aged 25 years and older with type 1 diabetes.5 CGM may be helpful in children, teens, and younger adults, but the evidence for A1C lowering is less strong when compared to adults with type 1 diabetes.23 Finally, CGM can be a supplemental tool to SMBG in patients with frequent episodes of hypoglycemia and hypoglycemia unawareness.5 The American Association of Clinical Endocrinologists (AACE) suggests the use of CGM in patients with type 1 diabetes who have unstable control or in those patients not able to achieve an acceptable A1C.24 The AACE guidelines do recognize the ability of CGM to detect unrecognized nocturnal hypoglycemia and postprandial hyperglycemia.
Summary
There are eight different classes of oral antihyperglycemic agents for the treatment of diabetes, and CGM offers new technology for monitoring. It is an exciting time for patients with diabetes and the providers who manage them. Just as home blood glucose monitors opened the door to more accurate and reliable testing, CGM connects the dots to provide the whole picture. But as health care providers must teach compliance to diet, exercise, and medications, we must now encourage our patients to use technology.
Studies suggest CGM is helpful in decreasing glucose excursions and stabilizing levels. CGM is useful in providing early warning for patients experiencing hypoglycemia and hyperglycemia. Patients and providers can also discover the effects of diet, exercise, lifestyle, and medication on glucose levels. As a diagnostic tool, CGM can assess treatment regimens for oral antihyperglycemics and insulin therapy. For the first time we have the ability to assess treatment regimens and change what is not working. When patients choose to purchase a CGM system, they can enhance their glycemic control on a continual basis.
Current devices are not accurate enough to replace traditional blood glucose testing, but the future holds endless possibilities as technology improves. There are studies under way that would fully integrate insulin pump systems and CGM to control the flow of insulin, a technology called a closed-loop system.25 CGM technology offers patients with type 1 or type 2 diabetes a new avenue to obtain good glycemic control.
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