Since the discovery of insulin, the management of type 1 diabetes

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1 SPECIAL Clinical FEATURE Review Realistic Expectations and Practical Use of Continuous Glucose Monitoring for the Endocrinologist Irl B. Hirsch University of Washington School of Medicine, Seattle, Washington Context: Real-time continuous glucose monitoring (CGM) has been available for type 1 diabetes for several years. This paper is a status report on our early experiences with this next technology. Evidence Acquisition: The two major sources of data acquisition included PubMed search strategies and personal experience of the author from clinical experience. Evidence Synthesis: Data assessing CGM accuracy, short-term outcomes (12 wk), and longer term outcomes (6 months) are reported. Potential strategies for successful and efficient use in an office or clinic setting are also discussed. Practical aspects of CGM use (alarm settings, using glycemic trending information) are also reviewed. Conclusions: Accuracy of this technology has improved in the short amount of time it has been available. Six-month data suggest that patient selection is a key for success. Patients who do not understand or practice the basics of intensive insulin therapy have the greatest challenges. Those who do best watch the receiver frequently, continue with frequent home blood glucose monitoring, use the trending information to make insulin adjustments, and understand the limitations of the technology. With insurance reimbursement improving, CGM is gaining acceptance as an important tool for the management of type 1 diabetes. Like home blood glucose monitoring and insulin pump therapy, this technology by itself is not a panacea for diabetes control. However, it further adds to our ability to improve the lives of people with diabetes. Long-term, the hope is that this technology will pave the way for a closed-loop device. (J Clin Endocrinol Metab 94: , 2009) Since the discovery of insulin, the management of type 1 diabetes has been a challenge. Unfortunately for some, many of our treatments today do not strictly meet the definitions of evidenced-based medicine. Indeed, we don t have appropriate randomized controlled trials about the use of insulin to prolong life, let alone many of our tools and strategies that many patients and providers have found beneficial. Our previous attitudes are not sustainable in today s environment, which makes currentday technology all that more difficult to study because the philosophy of yesterday s therapies is the basis of clinical care today. It is unlikely that basic concepts of insulin therapy used by many will ever be studied by today s standards of clinical trials. It is with this background that we have entered a new era for the management of type 1 diabetes. In late 1999, we started using our first retrospective continuous glucose monitors [Continuous ISSN Print X ISSN Online Printed in U.S.A. Copyright 2009 by The Endocrine Society doi: /jc Received December 2, Accepted April 15, First Published Online April 21, 2009 Glucose Monitoring System (CGMS), MiniMed Technologies; Medtronic Diabetes, Northridge, CA]. Using a sensor coated with glucose oxidase, the primitive system measured interstitial fluid glucose to provide a 3-day history of glycemia. Although there were challenges during the first part of the decade with this new technology, as expected it did improve in terms of size and accuracy. Reimbursement was inconsistent, and evidence of its effectiveness was limited (1, 2). A decade ago, the first real-time continuous glucose monitoring (rt-cgm) device was approved. Called Glucowatch, this device had numerous problems and did not survive. By the middle of this decade, rt-cgm as we know it now was approved. Although the technology itself has improved, perhaps more important has been our increased understanding of how best to use it and for which patients. This would also include Abbreviations: A1C, Glycosylated hemoglobin; CGM, continuous glucose monitoring; CSII, continuous sc insulin infusion; MAD, mean absolute difference; MARD, mean absolute relative difference; MedAD, median absolute difference; MedARD, median absolute relative difference; rt-cgm, real-time CGM; SMBG, self-monitoring of blood glucose jcem.endojournals.org J Clin Endocrinol Metab. July 2009, 94(7):

2 J Clin Endocrinol Metab, July 2009, 94(7): jcem.endojournals.org 2233 which patients are the best candidates for rt-cgm. For example, in the first randomized and controlled 6-month trial of use of sensor-augmented pump therapy compared with continuous sc insulin infusion (CSII) alone [sensor-augmented pump therapy for A1C reduction (STAR 1)], there were no differences in glycosylated hemoglobin (A1C) levels at the end of the 6-month trial (3). Adults and adolescents in this trial at baseline had a mean A1C level of 8.4%. In contrast, in the recent Juvenile Diabetes Research Foundation (JDRF) sensor study (4), adults 25 yr of age and older using rt-cgm (using either CSII or multiple daily injections) had a significant 0.53% reduction in A1C compared with control patients. Importantly, in this latter study, mean A1C at baseline was 7.6%. Furthermore, post hoc analyses for both of these trials concluded that those subjects who were not committed to wearing the device did not benefit (5), whereas those who were committed had improvements in the primary outcome. The technology works when it is used. The conclusion is that like CSII therapy, benefit can be predicted by appropriate patient selection. The significance of this is that there does indeed appear to be a clinical role for rt-cgm, and as the technology improves in accuracy and simplicity the indication will only increase. Similar to self-monitoring of blood glucose (SMBG) over 25 yr ago, it is now dependent on the physicians seeing these patients to ensure that they understand how to best use this new tool with their patients for maximum benefit. Mechanism and Accuracy Our current devices are based on the premise that interstitial fluid glucose is related to blood glucose due to diffusion across the capillary wall. There are currently three systems on the market using two different technologies. Sensor devices developed by Dexcom (San Diego, CA; Dexcom SEVEN) and Medtronic (Paradigm Real-Time and Paradigm Guardian) use a glucose oxidase methodology. The enzyme is embedded onto the sensor so that glucose and water will form gluconic acid and hydrogen peroxide. Under a basal electric current, the hydrogen peroxide dissociates, and a modified charge is produced directly proportional to the concentration of the glucose. The other available method from Abbott Diabetes Care (Alameda, CA), termed wired enzyme technology for their sensor (Freestyle Navigator), uses glucose oxidase coupled with osmium-based mediator molecules anchored on a polymeric backbone film (6). The term real-time is somewhat of a misnomer due to a time lag between the measurement of the interstitial fluid glucose and the display on the sensor receiver (7). This lag is typically anywhere from 7 to 15 min, although this appears to be significantly shorter with the current Dexcom device (8). Accuracy, especially with the first rt-cgm devices, was also problematic to the point that the Food and Drug Administration (FDA) would not allow any device to be used as a stand alone device, i.e. decisions about insulin dosing could not be made based on the rt-cgm result but rather based on traditional SMBG. Although these devices are quickly improving in accuracy, to date there has been no change from the FDA in the labeling of these devices, which are intended for use with traditional home blood glucose monitoring. Furthermore, some of the perceived accuracy concerns may be partly due to lag time. There are several accepted approaches for comparing rt-cgm devices with traditional references(9). The most commonly used are mean absolute difference (MAD), mean absolute relative difference (MARD), median absolute difference (MedAD), and median absolute relative difference (MedARD). MAD and MedAD are computed as the mean/median of the absolute values of the differences between sensor readings and reference blood glucose values. MARD and MedARD are the absolute differences expressed as a percentage of the reference blood glucose values (9). Finally, the International Standards Organization (ISO) criteria call for the percentage of CGM readings within 0.8 mmol/liter from reference when the reference is less than 4.2 mmol/liter or within 20% from reference when the reference is more than 4.2 mmol/liter (10). In one accuracy study, four different types of CGM devices were tested for accuracy in 34 individuals using euglycemic and hypoglycemic clamps (9). Results for the three devices available in the United States are shown in Table 1. Although this report suggests that the Dexcom device may be less accurate, there are methodological concerns with this study, especially with the hypoglycemic clamps, in addition to the fact the Dexcom system used in this study is an older version (11). Furthermore, a more TABLE 1. Accuracy of three CGM devices (adapted from Ref. 9) Guardian (Medtronic) Dexcom STS (Dexcom) Navigator (Abbott Diabetes Care) Point accuracy euglycemia (blood glucose mmol/liter) MAD (mmol/liter) MARD MedAD (mmol/liter) MedARD ISO: % reading within 20% of reference when reference is 4.2 mmol/liter Point accuracy hypoglycemia (blood glucose 2.5 mmol/liter) MAD (mmol/liter) MARD MedAD (mmol/liter) MedARD ISO: % reading within 0.8 mmol/liter of reference when reference is 4.2 mmol/liter

3 2234 Hirsch Understanding Continuous Glucose Monitoring J Clin Endocrinol Metab, July 2009, 94(7): recent report using a later generation Dexcom device suggested improvements in accuracy with the newer technology (12). Practical Aspects of Using rt-cgm It should be noted that we have very little experience using this technology in patients with type 2 diabetes, including those individuals receiving insulin. The technology is too new to have clinical trials assessing different strategies for effectiveness, although a group of clinicians reviewed their early experience (13). Patient selection It appears that like CSII therapy, individuals wishing to use rt-cgm require understanding and implementation of the basic principles of insulin therapy for type 1 diabetes (Table 2) (14). Patient (and provider) motivation is also critical. It needs to be emphasized again that none of the philosophies for insulin use in type 1 diabetes have been studied with the current-day criteria for effectiveness. Furthermore, many patients find some of these ideas too cumbersome. Nevertheless, despite the lack of formal randomized trials for our strategies of type 1 diabetes therapy, these appear to be the current practices of most clinical diabetologists and patients using modern-day insulin therapies It is doubtful that appropriate clinical trials for many of our intensive insulin strategies, particularly pump use, will ever occur. Individuals concerned about using a new management tool may find rt-cgm difficult. Due to the current status of this technology with regard to blood to interstitial fluid lag time and accuracy, some patients find these problems unacceptable. Related to this, some find it difficult to pay more attention to the trend as opposed to the specific number reported on the CGM receiver. As noted above, particularly during rapid glycemic changes, the actual blood glucose value may be significantly different than what is reported on the CGM receiver, and patients who only react to this number as opposed to measuring a capillary blood glucose measurement may give an inappropriate dose of insulin. On the other hand, knowing that a trend is upward or downward can suggest to the patient that an increase or decrease in insulin dose may be required. We generally advise a 10 20% change with unstable glycemia. All of these items are issues that can be discussed with individual patients. Perhaps more importantly, patients who are both motivated and willing to change certain behaviors are the ones who do best. Of all of the behaviors that can be seen to change, our anecdotal experience suggests that the most common are a reduction of overall carbohydrate consumption and waiting a significant TABLE 2. Predictors of rt-cgm success Understanding the basics of intensive insulin therapy Little fear of new technologies Understanding that the trend of the glucose rise or fall is more important than the glucose number displayed on the receiver Willingness to change diabetes treatment when CGM device clearly shows previous behaviors result in erratic glucose control Frequency of sensor use time interval between the prandial insulin and eating ( insulin lag time ) (14). The other major factor predicting individual patient success is frequency of sensor use. Wearing the device at least 60% of the time predicted significant A1C reduction in the STAR 1 study (3). In the larger JDRF randomized controlled trial, the group with the greatest success (those over 25 yr old) also had the greatest frequency of sensor use because 83% of the subjects wore the device at least 6 d each week (4). Importantly, the group with the least success, those between the ages of 15 and 24 yr, was reported to have only 30% of subjects wearing the device at least 6 d each week. The next issue to consider is whether rt-cgm would be better used integrated with CSII or used alone with multiple daily injections. One could make arguments either way. For example, for frequent small doses of insulin to treat upward glycemic trends, using a pump would be much more convenient. As of this writing, there is only one CGM device that is integrated with an insulin pump (Medtronic), but that should change in the near future with other CGM systems communicating with CSII devices. However, it should also be noted that some patients have difficulty being attached to anything and dislike any type of indwelling catheter, even if sc. Therefore, this issue is quite patient specific and was not specifically addressed in the JDRF randomized controlled trial where both treatment modalities were used (4). Many patients using CGM with multiple daily injections do extremely well, and CSII should not be seen as a prerequisite for successful use. Finally, it needs to be appreciated that as of now all sensors and pumps require separate insertion sites, and the problem of having enough accessible sc tissue is problematic in younger pediatric patients. Physician clinic and office considerations Similar to any procedure, physicians need to work in an appropriate environment with an infrastructure allowing efficient management of patients. This is no different than the management of CSII patients. It also needs to be appreciated that in general, particularly for patients receiving insulin, blood glucose meter downloading allows observation of patterns not generally seen with written log books (15). Unfortunately, even this does not often occur in the offices of clinicians seeing many patients with diabetes. Anecdotal surveys in the United States suggest that few endocrinologists download blood glucose meters (let alone pumps and CGM devices), although downloading seems to have become more widespread in the offices of pediatric endocrinologists. Although there are no randomized trials assessing patient outcomes with the presence or absence of downloaded glucose meters, insulin pumps, or CGM devices on a regular basis, in the JDRF CGM trial all patients had their diabetes management reviewed by their clinicians after downloading of all of the available data (4). Patients can often download their CGM devices at home with software provided by the respective companies. When this is done, much of the burden of the time for the download itself in the office can be reduced. Furthermore, many patients find reviewing their downloaded CGM devices at home even without physician or nurse involvement can be quite helpful for identi-

4 J Clin Endocrinol Metab, July 2009, 94(7): jcem.endojournals.org 2235 fying patterns they wouldn t appreciate otherwise. Again, this point has not been studied specifically. Many endocrinologists find it helpful to have one or two individuals (usually a medical assistant) in the office trained to perform the download. The time it takes to download these devices varies by the amount of data stored and the brand of the device. In general, including printing time, blood glucose meters are the quickest (usually 1 to 2 min), with CGM devices the slowest (5 to 15 min). Insulin pumps tend to be intermediate. Certainly, the speed of the computer will influence these times. A more fundamental issue is the need for a true diabetes team to assist in both the education and management of these patients. One could argue that the true multidisciplinary diabetes team (16) with nurses, nutritionists, and psychologists as popularized in the 1980s and used in the Diabetes Complications and Control Trial is not financially realistic in the world of diabetes reimbursement in Although this is a valid concern, it should be possible to manage these patients efficiently. Referral to industry trainers, hospital-based nurses, and nutritionists and use of part-time diabetes educators works for many. Still, the economics of rt-cgm and intensive insulin therapy in general is a topic that requires much more thought by organizations such as The Endocrine Society, the American Association of Clinical Endocrinologists, and the American Diabetes Association. Specifics for initiating rt-cgm Similar to CSII, we have started pre-sensor classes to initiate patients better to the use of rt-cgm. Typically, six to eight patients with family members attend these classes which last anywhere from 60 to 90 min. Patients are shown each CGM device and are allowed to learn each of their features. Importantly, realistic expectations for all of the devices are emphasized. Similar to pumps, the decision about which CGM device to purchase is made by the patient. Specifics about each device are shown in Table 3. There are certain keys to success. First, calibration should ideally be performed when glucose levels are relatively stable (for example, the rate of change of glucose 1 mg/dl min). The morning, when fasting glucose can be measured, is often a good time for calibration. As noted above, the Dexcom has reported that the calibration timing may not be as important (8). Next, specific targets should be individualized. These targets are goals that are individualized and programmed into the CGM receiver and download report. These targets may be higher for patients with hypoglycemia unawareness or lower for a pregnant woman. The download will be able to note the percentage of time below, within, or above the target. Perhaps more important are the threshold glucose alarms that are present on all currently available devices (Table 3). These alarms alert the patient with either a beep or vibration when the glucose level either rises above or drops below whatever the threshold target is programmed. It is important to appreciate that the sensor lag time will result in a delay for when that threshold is reached. This is particularly important for deciding where TABLE 3. Features of the three currently available rt-cgm devices Abbott Navigator Dexcom SEVEN PLUS Medtronic Paradigm Real-Time or Guardian Real-Time a Range of glucose values mg/dl mg/dl mg/dl Life span of sensor 5 d 7 d 3 d Warm-up period 10 h 2 h 2 h Calibration frequency After sensor insertion: 10 h, 12 h, 24 h, 72 h Every 12 h Every 12 h SMBG device FreeStyle (built-in) Any available commercial meter. One-Touch (or can enter manually) One-Touch UltraLink (or can enter manually) Alarms Alarm frequency Hypoglycemia and hyperglycemia (adjustable). Predictive alarms based on rate of change Hypoglycemia: repeats every 5 min until alarm acknowledged (or glucose rises above target); then every 15 min until glucose rises above target; cannot be muted. Hyperglycemia: repeats every 5 min until alarm acknowledged (or glucose decreases below target); then every 15 min until glucose decreases below target; can be muted Hypoglycemia and hyperglycemia (adjustable and customizable types to differentiate between high and low). Optional rate of change alarms. Hypo safety alarm set at 55 mg/dl. No predictive alarms Hypoglycemia: every 5 min ( 3) until alarm is acknowledged, then every 30 min when below target (customizable). Another alarm present at 55 mg/dl. Hyperglycemia: every 5 min until alarm is activated. Snooze alarms can be set from 30 min to 5hto realert Hypoglycemia and hyperglycemia (adjustable). Predictive alarms based on rate of change only with Guardian Real-Time. Can be set as snooze alarm. Hypoglycemia: 5 to 60 min. Hyperglycemia: 5 min to3h. Trend arrows Yes Yes Yes Ability to enter events Insulin, meals, exercise Yes Insulin, meals, exercise Initial cost of device $1250 $1248 $1200 (Guardian Real- Time only) Monthly sensor cost b $ $ $ a Medtronic Guardian Real-Time is a CGM device, whereas the Paradigm Real-Time is a CGM device combined with an insulin pump. b Based on prolonged (from patient experience) and approved (based on product labeling) use.

5 2236 Hirsch Understanding Continuous Glucose Monitoring J Clin Endocrinol Metab, July 2009, 94(7): to set the low glucose alarm. If set too low (e.g. 60 mg/dl), it is possible the actual blood glucose is significantly lower if the rate of change is rapid (e.g. 2 mg/dl min). This would not be a good situation for someone with hypoglycemia unawareness. On the other hand, if set too high (e.g. 90 mg/dl), the alarm is going off frequently and now is considered a nuisance alarm by some. Still, some clinicians initiate this low alarm at this level or higher. Appropriate trials would be welcomed on this point. Obviously, for now compromises need to be made so that when the alarms are set off they are relevant and the patient takes appropriate action. For the high alarm we have learned that patients starting with A1C levels above 8% need to have the alarms set high enough that it is not being activated constantly. For this population, especially when initiating rt-cgm, we tend to set the high alarms between 250 and 300 mg/dl but then quickly lower the level once the patient learns how to use the device. Although the ideal alarm levels have not been studied, most of our patients have their low alarms in the 70 to 80 mg/dl range, with the high alarms ranging from 180 to 220 mg/dl. The predictive alarms present with the Navigator and the Guardian Real-Time may be helpful in alerting patients, based on the rate of glucose level rise or fall, when the glucose will be above or below a target. Again, this feature has not been formally studied, but our experience has been quite positive. Practical tips for successful use of rt-cgm Perhaps the most important behavior is simply watching the device on a regular basis. As with all other aspects of the use of rt-cgm and insulin therapy in general, this has never been studied. Taking advantage of glucose trending requires more attention than the traditional before-meal and bedtime SMBG. The frequency of CGM device observation was not specifically studied in the STAR 1 or JDRF trials, but anecdotally we have found those who have done the best are watching it frequently, once or twice each hour. Other areas to ensure successful use of rt-cgm is the timing of the calibration as noted above. Although SMBG is usually performed many times each day by these patients before beginning rt-cgm, many are not aware of all of the factors that impact the accuracy of SMBG results (17). Perhaps a greater unrecognized problem is unclean hands. When an inaccurate capillary glucose measurement is used for a CGM calibration, the device will likely be inaccurate until the next calibration. Another behavior concern often seen is patients performing the minimum of SMBG tests to maintain their calibration. It should be recalled that insulin dosing decisions are not approved from the CGM device; the current generation of CGM is to be used in conjunction with SMBG measurements. This often doesn t happen, and we frequently see reduction in SMBG usage when we download the blood glucose meters. It is admittedly difficult to convince some patients to increase their SMBG frequency to pre-cgm levels. Reduced SMBG monitoring may be especially risky near the end of the sensor life when accuracy of the CGM may not be as good. It should be noted that the most common practical point about this is that most often the end of the sensor life is well after the labeled recommendation for sensor use. For example, in a study of 30 patients the Dexcom device was shown to have similar accuracy after insertion 3 d after the labeled life of the sensor (18). Perhaps the most important place the current generations of CGM devices can be used is with providing trending information to the patient. As an example, if the blood glucose is 120 mg/dl before a meal, most patients will provide the appropriate insulin for that meal based on the carbohydrate content of that meal. In this example, 6 U of insulin are provided for 60 g of carbohydrate. But what if at that same blood glucose level the rate of change of that blood glucose was either increasing or decreasing by 1 or 2 mg/dl min? Would it still be appropriate to provide the same 6 U of insulin? For both of these situations, different doses of insulin should be provided due to the fact with simple SMBG we generally are not able to incorporate rate of change in the insulin dose. Patients using CGM are taught that with an increase of glucose by more than 1 but less than 2 mg/dl min they should increase or decrease their insulin dose by 10% based on the direction of the trend. Upward trends require more insulin, whereas downward trends require less. With glucose rates increasing or decreasing by more than 2 mg/dl min, we ask patients to increase or decrease their insulin dose by 20%. There have been no formal studies about this important point, but these types of algorithms were also used in the STAR 1 and JDRF CGM trials. Insulin dosing during nonstable glycemia The issue of insulin dosing using rate of change of glucose also needs to be considered for non-meal times. Due to the relatively FIG. 1. Data are shown for a 39-yr-old man on an insulin pump. Top, Blood glucose data with the blue line representing what the patient sees for real time continuous glucose measurements. The target glucose is mg/dl. Bottom, Basal and bolus insulin use from the pump. The y-axis on the left represents the basal insulin, which is constant at 1.0 U/h. The y-axis on the right represents bolus insulin. Just after 1800 h (time point a ), he measures a blood glucose that is approximately 140 mg/dl. At that time, he administers about 8 U of insulin through his pump. Just before 2200 h (time point b ), the alarm goes off as the glucose now spikes above 200 mg/dl. Based on the insulin-on-board and the glucose, the pump calculates that about 2 U of insulin be given at that time. However, the pump calculator does not take into account the upward trend of the glucose, and thus the glucose level is not corrected. Two hours later, the alarm is set off again (time point c ), and now more insulin is required. The glycemic exposure could have been reduced if more insulin was provided at time point b than originally recommended.

6 J Clin Endocrinol Metab, July 2009, 94(7): jcem.endojournals.org 2237 FIG. 2. Data are shown for a 61-yr-old woman with a 6-yr history of type 1 diabetes. Rt-CGM shows how she keeps her glucose levels above the target due to her extreme fear of hypoglycemia. Note that on one day between 1500 and 1600 h her glucose level came down into the normal range. After she noted this, she intentionally ate to bring her glucose level back to the hyperglycemic range. FIG. 3. Data are shown for a 42-yr-old man with a 30-yr history of type 1 diabetes wearing a sensoraugmented pump. Note that just before 2200 h (panel A) he takes 1.5 U of insulin when the alarm sounds for a glucose rising above 200 (time 8 in the tracing). Cereal and milk were eaten about 1 h after that (time 10 in the tracing), and 3.5 U of insulin were provided. Two hours after the first alarm, the alarm sounds again (due to continued elevation of the blood glucose), and now 2.5 U of insulin are infused. However, although he is above his target causing the alarm to be activated, the trend is coming down; thus the large dose of insulin was not required. After going to sleep (panel B), his glucose level falls below 70 mg/dl. This results in the alarm sounding around 0100 h. He only eats a small piece of fruit before going back to sleep. However, all of the insulin stacked from the night before results in hypoglycemia throughout the early morning, and he does not awaken from the alarms until just before 0400 h, when he has a large snack. prolonged pharmacodynamics of the rapid-acting insulin analogs (14), when do we best give additional insulin with upward trends after a meal? How do we prevent insulin stacking from the previously administered insulin to prevent hypoglycemia? There is no consensus on this point, but in our clinic we ask patients not to administer additional insulin for at least 1 h after the mealtime insulin. Our initial observation is that by this time there is at least enough of the insulin and carbohydrate absorbed that most patients can make reasonable estimates for additional insulin dosing. Obviously, this is easier with a pump, but we have many patients who give these between meal touch-ups with pens containing a rapid-acting insulin analog. The amounts of these insulin doses are by necessity empirical, but any miscalculations from this often trial and error methodology can be rectified by simply watching the sensor once or twice each hour. Typically, most patients with type 1 diabetes will require smaller doses (0.5 to 1.0 U) when closer to a meal to correct the hyperglycemia or hyperglycemic trend due to greater insulin availability from the previously administered mealtime insulin. This dosing strategy should be reviewed with the patient during follow-up visits. As an example, Fig. 1 shows a patient using an insulin pump and wearing a sensor. His fundamental problem is he underdosed his meal, resulting in a hyperglycemic alarm to sound. He used his bolus calculator on his pump to provide him with the appropriate dose of insulin based on the blood glucose and the amount of insulin-on-board (14). Unfortunately, the calculator on the pump underdosed and miscalculated the amount of insulin actually needed to correct the glucose because the upward trend of the glucose is not considered by the pump software. With an upward trend, more insulin than initially calculated by the pump software is required to correct the hyperglycemia. There are situations when retrospectively reviewing CGM downloads can be helpful. For example, Fig. 2 shows a 61-yr-old woman with type 1 diabetes and an A1C of 8.3%. The download suggested extreme fear of hypoglycemia as her primary reason for not being able to manage her diabetes better. Figure 3 repre-

7 2238 Hirsch Understanding Continuous Glucose Monitoring J Clin Endocrinol Metab, July 2009, 94(7): sents a 42-yr-old man on a sensor-augmented pump. He stacks his insulin as his glucose level is dropping near bedtime resulting in hypoglycemia overnight. Of further concern is the fact that he sleeps through most of the alarms that are activated every 20 min. This case emphasizes how this technology may not be as helpful for a sound sleeper like this, but also how reviewing the mistakes made with insulin dosing the night before can hopefully prevent this from occurring in the future. Conclusions There clearly is a clinical role for rt-cgm in the management of appropriate patients with diabetes. Some would argue that it is quickly becoming the standard of care for many patients. However, this is a young technology, and further improvements should allow more patients to benefit. This means that clinicians will be required to stay up-to-date as improvements in this care improve. rt-cgm is expensive, yet more insurance companies are reimbursing for the ongoing cost of the sensors. Like many technologies, the goal for the clinician is to ensure that appropriate patients who can most benefit from rt-cgm are provided the opportunity to use it. Furthermore, clinicians who see this population of patients should ideally have an infrastructure in their offices and clinics to see these patients as efficiently as possible. Unfortunately, until there is better reimbursement for the clinicians and their office staff, uptake of rt-cgm likely will lag behind its potential. Nevertheless, this is an exciting time in the treatment of diabetes as the technologies continue to improve, permitting more patients to reach glycemic targets without increasing, or even potentially decreasing, the risk of hypoglycemia. Finally, it should be realized that rt-cgm by itself will likely not be an end of this technology, but rather just the beginning as research continues to hopefully close the loop for the treatment of type 1 diabetes. Acknowledgments I thank Carol A. Verderese for her editorial assistance in the preparation of this manuscript. Address all correspondence and requests for reprints to: Irl B. Hirsch, M.D., University of Washington Medical Center-Roosevelt, 4225 Roosevelt Way NE, Suite 101, Seattle, Washington ihirsch@ u.washington.edu. Disclosure Summary: The author is a consultant with Johnson & Johnson and Roche Diagnostics. References 1. Guerci B, Floriot M, Böhme P, Durain D, Benichou M, Jellimann S, Drouin P 2003 Clinical performance of CGMS in type 1 diabetic patients treated by continuous subcutaneous insulin infusion using insulin analogs. 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