10.1177/0897190003261306 BRIGGS SELF-MONITORING AND CORNELL BLOOD GLUCOSE

ARTICLE

Self-monitoring Blood Glucose (SMBG): Now and the Future Amber L. Briggs, PharmD, and Susan Cornell, BS, PharmD, CDE, CDM

In 2002, the cost of diabetes in the United States reached $132 billion. There is a well-established relationship between blood glucose control and the risk of diabetes-related complications. Tight blood glucose control, through intensive diabetes therapy, reduces the risk and delays the onset of diabetesrelated microvascular complications. Regular and consistent self-monitoring of blood glucose (SMBG) is and should be a part of all diabetes disease state management programs. Pharmacists can truly increase the numbers of patients who

use SMBG by being aware and familiar with the monitoring devices available to patients and identifying the physical and psychological issues surrounding SMBG. Results from SMBG and hemoglobin A1C are the basis for most of the medical decisions made for patients with diabetes. This review discusses the best time for patients to test their blood glucose, information regarding blood glucose monitoring devices, alternative site testing, and the newest technology available in glucose monitoring.

KEY WORDS: Self-monitoring blood glucose, diabetes, meters, blood glucose

INTRODUCTION Diabetes mellitus is a chronic metabolic disease affecting 17 million Americans.1 The total cost of diabetes in the United States in 2002 reached $132 billion. This number includes $91.8 billion in direct medical costs and $40.2 billion in disability, work loss, and premature mortality.2 There is a well-established relationship between blood glucose control and the risk of diabetes-related complications.3 Tight blood glucose control, through intensive diabetes therapy, reduces the risk and significantly delays the onset for diabetesrelated microvascular complications as demonstrated by the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS).3-5 Reducing the complications of diabetes through glucose control can reduce diabetes health care costs in the United States. Intensive management of blood glucose as defined by the American Diabetes Association (ADA) is in reference to a fasting blood glucose of 90 to 130 mg/dL, postprandial blood glucose of < 180 mg/dL, and A1C < 7.0%. However, the American Association of Endocrinologists recommends tighter control, supporting blood glucose goals of ≤ 110 mg/dL fasting, ≤ 140 mg/ dL 2 hours postprandial, and A1C < 6.5%.6 Patient participation in his or her diabetes management through SMBG is necessary to achieve optimal blood glucose levels. SMBG is a key component in diabetes self-man-

agement education.7,8 Despite education, few patients self-monitor their blood glucose levels on a regular basis or adhere to the SMBG regimen prescribed by their health care providers.9,10 Achieving tight glucose control as demonstrated in DCCT and UKPDS could not have been accomplished without patients monitoring their own blood glucose levels. This review discusses the best time for patients to test their blood glucose, information regarding blood glucose monitoring devices, alternative site testing, and the newest technology available in glucose monitoring.

To whom correspondence should be addressed: Amber L. Briggs, PharmD: e-mail: [email protected]; Midwestern University e-mail: [email protected]. Amber L. Briggs, PharmD, assistant professor of pharmacy practice, Midwestern University, Chicago College of Pharmacy, Department of Pharmacy Practice, 555-31st Street, Downers Grove, IL 60515; clinical pharmacist, Community Pharmacy Practice Residency Program primary preceptor, Dominick’s Pharmacy, 1968 Sibley Blvd Calumet City, IL 60409. Susan Cornell, BS, PharmD, CDE, CDM, assistant director of experiential education and assistant professor of pharmacy practice, Midwestern University, Chicago College of Pharmacy; clinical pharmacist and educator, Dominick’s Pharmacy. JOURNAL OF PHARMACY PRACTICE 2004. 17;1:29–38 © 2004 Sage Publications DOI: 10.1177/0897190003261306

BRIGGS AND CORNELL

WHEN TO SMBG The ADA recommends a minimum of once-daily monitoring for patients on insulin and sulfonylureas to assist in the prevention of hypoglycemia. The number of times per day a patient self-monitors is specific to the patient’s needs and based on the practitioner’s recommendations. However, to obtain optimal glucose control, it is necessary for a patient who uses insulin therapy to test a minimum of 3 times per day. Any patient who is experiencing stress, illness, or changes in medications should also test more often.3,9 Patients currently on insulin therapy, including women with gestational diabetes mellitus, need to test SMBG more frequently than those who are on oral medication and/or medical nutritional therapy alone.9,11 When patients are adjusting insulin based on meals, they should test before meals and at bedtime. For patients on a fixed insulin-dosing regimen, testing 2 to 4 times per day is recommended. When experiencing uncontrolled blood glucose swings, patients should test a minimum of 4 times per day. The benefit of testing 2 hours after a meal (ie, postprandially) provides information in regards to the effect of food intake on glycemic control. It is especially important to test postprandially in a person with type 2 diabetes because this time of day tends to be most problematic for this population. A blood glucose measurement at 3 or 4 AM may be necessary to determine if the patient is experiencing the dawn phenomenon or Somogyi effect. Patients who use SMBG are provided with immediate feedback concerning glycemic control. They are able to evaluate diet and physical activity effects and adjust lifestyle factors to assist in the management of their diabetes goals based on blood glucose measurements.3,9 Patients diagnosed with type 2 diabetes should test their blood glucose levels based on the oral agent prescribed.12 Table 1 recommends the appropriate time to check blood glucose levels based on mechanism of action of the oral agents prescribed. METER CONSIDERATIONS AND CHOICES Pharmacists are in an excellent position to provide diabetes education and management for patients. The first place pharmacists can start is in assisting patients in choosing an appropriate meter for them. This should include a demonstration of the meter to the patient, a review of the patient’s technique, and an understanding through the show-and-tell method where the patient demonstrates appropriate use of the meter back to

30 • JOURNAL OF PHARMACY PRACTICE 2004(17.1)

the pharmacist. This portion of diabetes education can be accomplished in even the busiest of pharmacies. More than 25 blood glucose meters are commercially available. Meters differ in the amount of blood needed for each test, testing speed, overall size, ability to store test results in memory, technology, and cost and test strips used. Blood glucose monitors function by 1 of 2 mechanisms, reflectance (photometric) or electrochemical (amperometric). Reflectance meters measure the whole blood sample by the blood reacting with an enzyme on a blood strip and causing a color change on the strip. The electrochemical meter uses only a small portion of the blood sample that is generated through an electrical charge. Newer technology has allowed SMBG devices to use smaller blood samples than in the past.13 The Food and Drug Administration requires all meters to have an error rate of < 20% at blood glucose levels of 30 to 400 mg/dL. The ADA prefers the error rate to be < 10% at the same blood glucose levels. The TheraSense FreeStyle™ and the LifeScan OneTouch Ultra™ demonstrated 98.8% and 98.4% accuracy, respectively, in an error grid analysis.14 Proper technique includes correct calibration, sample size, and performance of the overall test.3,9 User errors are the number one cause of inaccurate blood glucose readings.15 Skeie et al demonstrated error rates are higher in patients than laboratory technicians (7%20% versus 2.5%-5.9%).16 Patients need to demonstrate proper SMBG testing technique to a pharmacist or other health care provider to ensure the accuracy of the proper testing technique for using blood glucose meters. Health care providers should help patients develop a simple checklist for each patient to follow in the areas of (1) preparation, (2) aseptic technique, (3) puncture site identification, (4) obtaining blood, (5) application, (6) record keeping, and (7) cleanup. If everything appears to be functioning correctly with the meter, yet the patient is still experiencing difficulty with the results, the health care provider may identify the source of error. If there is a question concerning the accuracy of results, ask the patient to respond to the following questions: (1) Was the meter coded for a new vial of test strips? (2) Did the patient wash his or her hands prior to testing? Remember, glucose from food will affect test results. (3) Was the correct amount of blood applied to the test strip? (4) Were the test strips used prior to the expiration date? (Most strips are only good for 90 days after the vial is opened, so the patient should mark the vial with the date he or she opens the vial of strips.) (5) Were the test strips exposed to extreme temperature or humidity? Besides

SELF-MONITORING BLOOD GLUCOSE

Table 1 Timing of Self-monitoring Blood Glucose (SMBG) in Type 2 Diabetes12 Oral Product Sulfonylurea secretagogues Biguanides Thiazolidinediones Nonsulfonylurea secretagogues α-glucosidase inhibitors

Mechanism of Action Increase phase 2 insulin release Decrease hepatic production (gluconeogenesis) of glucose; increase insulin sensitivity PPAR-γ agonist (reducing resistance at the cellular level) Increase phase 2 insulin release (short acting ) Inhibitor of α-amylase and α-glucosidases

user error, other sources of error with blood glucose monitors are defective reagents, uncalibrated meter, and not storing meter or strips according to manufacturers’ recommendations.17-26 Accuracy of the blood glucose monitor readings is affected when a patient’s blood circulation is reduced, resulting in difficulty obtaining a blood sample. With inadequate blood sample sizes, the patient may receive an error message stating the reaction could not take place. If a reaction is able to take place, the meter’s alarm may not sound; however, the results may read falsely low. Results may also be falsely low if the patient is severely dehydrated, severely hypotensive, in shock, or in a hyperosmolar state (with or without ketosis). Critically ill patients should not be tested with home blood glucose meters. In addition, hematocrit (HCT) abnormalities can affect the results obtained from SMBG. HCT results less than 30% may cause falsely high readings, and HCT results greater than 55% may cause falsely low readings in LifeScan™ meters.27 Some of the newer meters are accurate with HCT ranges of 20% to 60%. Other factors affecting the accuracy of blood glucose meters include altitude, temperature and humidity, and triglyceride concentrations.28 Meters may have control solutions for low, normal, or high levels of glucose testing to test extremes of the meter’s capabilities. It is essential that the brand of control solution be specifically manufactured for use with the same brand of blood glucose meter. Instruct patients to use the same testing procedure with the control solution that is used when testing a drop of blood. Control tests should not be calculated in the patient’s blood glucose average; therefore, the patient needs to mark the test as a control. Consult the product’s user manual to determine the procedure for marking control tests. A common problem with SMBG devices is correctly coding the monitor to a new lot of strips. Monitors use several methods in coding procedures, which include buttons on the monitor, a chip provided with each box of test strips, barcodes on test drums, or coding strips

When to SMBG Fasting; postprandial Fasting Fasting; postprandial Postprandial Postprandial

within boxes of test strips. When reviewing SMBG technique, coding test strips should be a part of the evaluation of technique. When a patient is having trouble with the monitor (ie, erratic blood glucose measurements), this may be the source of the problem. Advise patients that they should complete a control test with each box of new strips.17-26 The Accu-Chek Compact™, Bayer Ascensia Dex™, and Bayer Ascensia Breeze™ use an automatic coding process to assist in limiting errors associated with coding.18,19,23 All meters use the whole blood concentrations from capillaries. Venous blood draws in the laboratory display blood glucose results in plasma concentrations. The erythrocyte glucose content is approximately 10% to 15% less in whole blood than plasma due to the dense nature of erythrocytes. Whole blood has approximately equal amounts of plasma and erythrocytes; therefore, the calculated difference between whole blood and plasma is 10% to 15%.9 Most of the newer meters will convert the whole blood results into plasma-calibrated results. Common barriers to testing, other than a lack in understanding of how to use the meter, include but are not limited to not comprehending the importance of testing, cost of the monitor and strips, lower social economic status, older age, fewer A1C tests, obesity and other comorbidities, poorer glycemic control, stigma attached to testing in a public place, finger-stick testing, and inconvenience.9,29 It may take several pharmacist appointments to address all the issues surrounding barriers to testing; however, the investment will be worthwhile due to the increase of patient testing, thereby improving glycemic control and reducing diabetesrelated complications. Overall, patient education concerning SMBG and the devices available plays the largest role in the success of SMBG.23 You may ask, What is the best meter available for patients with diabetes? The answer is always that the best meter available for a patient with diabetes is the one that he or she will use and use correctly. JOURNAL OF PHARMACY PRACTICE 2004(17.1) •

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SMBG devices are updating style and technology constantly to improve use of these meters and improve overall diabetes care. For example, the Accu-Chek Advantage™ has a new look, with new rubber grips and a slicker silver design for an updated appearance. Instructional materials with the products are easier for patients to read, including a first-time guide page to assist patients with their first use of an Accu-Chek™ product.30 For a product comparison, see Table 2. Self-monitoring can assist the patient in identifying and treating hypoglycemia; making changes and decisions on food choices, portions, or insulin adjustment; and managing a current illness. This information will allow the patient to see the relationship between food consumption and blood glucose levels. METER DOWNLOADING Most of the new meters available today have computer downloading capabilities. The software provides patients and health care providers alike the ability to download the information stored within the blood glucose monitor onto their computers. Trend chart and graph (ie, pie and bar graph) reports may be based on average highs and lows, insulin, and carbohydrates.17-26 TheraSense FreeStyle™ has a Web-based computer downloading program to allow immediate graphing, faxing, and e-mailing of glucose results to health care providers.31 Accu-Chek™ and TheraSense™ have programming for personal digital assistants (PDAs) to provide further information to the patients and practitioners concerning blood glucose control.21-24 To get the most of the information downloaded, be certain that the date and time on the monitor are correct. If the time on the meter is incorrect, the results downloaded will also be incorrect, especially in respect to fasting or postprandial data. Patients can purchase the software, download it from the companies’ Web sites, or come to the pharmacy for the monitor download service. See Table 3 for more information. Meter downloading before physician appointments provides the physician and pharmacist with pertinent information to make clinical decisions. Keep in mind that an electronic logbook is not the replacement for a written logbook. The patient’s explanation for blood glucose results provides useful information in making medical decisions for the health care provider, as well as supports an empowering behavior the patient can visualize daily.17-26 ALTERNATE SITE TESTING There is a move toward alternative ways of testing blood glucose to decrease the inconvenience, the time, 32 • JOURNAL OF PHARMACY PRACTICE 2004(17.1)

and the pain associated with traditional finger-stick blood glucose testing.9,32,33 The development of newer technology allows smaller samples of blood that in turn open the field for alternative site testing. Several blood glucose meters are approved for alternative site testing. These include OneTouch Ultra™, Accu-Chek Active™, Accu-Chek Compact™, TheraSense Freestyle™, Bayer Ascensia Elite™ CL, Bayer Ascensia Breeze™, and Bayer Ascensia Dex™. All these monitors are approved for forearm alternative site testing; however, recently, alternative sites such as the upper arm, thigh, calf, palm, and abdomen have been identified and approved (see Table 4). The meters approved for several alternative sites for testing are termed multiple site testing devices.17-19,22-25 There is controversy surrounding alternative site testing and whether there is accurate representation of the patient’s blood glucose state. There may be variations between the finger-stick and the alternative site readings, specifically during times of rapidly changing glucose levels (eg, immediately after a meal, after exercise). Several studies have been conducted to determine if there is a difference between alternative site and finger glycemic readings.34,35 There have been a few studies that have measured blood glucose using the TheraSense FreeStyle™ monitor from both the fingertips and forearms in patients with type 1 or type 2 diabetes.32,35-39 In a study of the alternative site testing with TheraSense Freestyle™ 32, the forearm was either rubbed or not rubbed prior to blood glucose test, and a test even included a test meal. Each patient had blood glucose measurements every 15 minutes from either the fingertip or the forearm. This assisted in answering the question of why there was variation at times between the 2 sites. The authors determined the variation that did occur between the 2 sites was directly related to the rapidly changing glucose levels. A lag time between finger and arm samples ranged from 5 to 20 minutes during glucose fluctuations and varied from patient to patient. This is what is now termed the lag time phenomenon. Recommendations were to not use alternative site testing during times of glucose fluctuation or variation. In addition, rubbing the alternative site appears to be beneficial in equalizing results. The theory that supports rubbing is that rubbing assists in increasing blood flow within the alternative site, bringing the blood to the surface. Patients seem to prefer alternative site testing (75% of patients) because it gave their fingers a rest. However, there was not a significant increase in the frequency of SMBG or a reduction in A1C.39 The SMBG instruction booklets warns patients there may be variation between finger site testing and alternative site testing. The manufacturers recommend

Table 2 13,17-26 Self-monitoring Blood Glucose Device Comparisons Accu-Chek™

Manufacturer Technology Battery Plasma calibrated versus whole blood Strips Sample size (mL) Blood on strip

Active

Advantage

Compact

Roche Reflectance 2-cr 2032 3V lithium Plasma

Roche Electrochemical 2 AAA

Roche Reflectance 2 AAA

Roche Electrochemical 2 AAA

Plasma

Plasma

Active 1 Capillary

Comfort curve 4 Capillary, can add on within 15 seconds No

Yes

Complete

BD Latitude/ Latitude™

Ascensia Elite XL™

Dex™

Plasma

BD Diagnostics Electrochemical 1-cr 2450 3V lithium Plasma

Bayer Electrochemical 2-cr 2032 3V lithium Plasma

Bayer Electrochemical 2-cr 2016 3V lithium Plasma

Compact 3.5 Capillary

Comfort curve 4 Capillary

BD 0.4 Capillary

Ascensia Elite 2 Capillary, action draw

Ascensia Dex 3 Capillary, action draw

Yes

No

No

Yes

Yes

Yes Automatic Automatic Press set button before test

No Chip Check strip After test event function L1 or L2

No Coding strip Bayer Electrochemical

No Automatic Automatic After test, push B button twice

100

1000

No Button on meter Automatic After test, use arrow until C appears 250

2-cr 2032 3V lithium Plasma

100

Alternative site testing Cleaning required Coding Calibration Control test marking

Yes Code key Automatic Press S button before or after test

Memory

200

No Chip Check strip Use check strip before marking control 100

Software

Compass

Camit Pro

Compass

Accutility

Languages Support Range (mg/dL)

Symbols 800-858-8072 10-600

Symbols 800-858-8072 10-600

Symbols 800-858-8072 10-600

4 800-858-8072 10-600

Strip expiration

Date on vial

Date on vial

Date on vial

Temperature range (°C) Humidity (%) Hematocrit (%)

10-40 (50-104°F)

14-40 (57-104°F)

3 months after opening 10-40 (50-104°F)

< 85 30-55

< 85 25-60, if < 200 mg/ dL; 20-55, if > 200 mg/dL

< 85 25-65

< 85 25-60, if < 200 mg/ dL; 20-55, if > 200 mg/dL

14-40 (57-104°F)

BD Diabetes Software, Diabetes Software Simplified Symbols 800-232-2737 20-600 3 months after opening 10-40 (50-104°F) < 85 20-55

Win Glucofacts

Ascensia Elite 2 mL Capillary action draw Yes

Symbols 800-348-8100 10-600 Date on foil packet

No

10-40 (50-104°F)

Coding strip Bayer

10-80 20-55

33

34

Table 2 (continued) Ascensia Breeze™ Manufacturer Technology

Bayer Electrochemical

Battery

1-cr 2025 3V lithium

Plasma calibrated versus whole blood Strips Sample size (mL) Blood on strip

Plasma

FreeStyle™ TheraSense Colometric; electrochemical 2 AAAA

FreeStyle Tracker™

OneTouch Basic

OneTouch Ultra/Ultra Smart

Precision QID

LifeScan Reflectance

LifeScan Electrochemical

Abbott Electrochemical

2 AA

1-cr 2032 3V lithium

Meter replacement

Plasma

LifeScan Colometric; electrochemical Dependent on personal digital assistant used Plasma

Whole blood

Plasma

Plasma

Ascensia Autodisk 2.5-3.5 Capillary

FreeStyle 0.3 Capillary, can add within 60 seconds

FreeStyle 0.3 Capillary, can add within 60 seconds

OneTouch 10 Hanging drop

OneTouch Ultra 1 Capillary

Precision QID 3.5 Capillary, action draw, can add within 30 seconds No

Alternative site testing Cleaning required Coding Calibration Control test marking

Yes

Yes

Yes

No

Yes

Yes Automatic Automatic After test, use arrow up key

Yes Button on meter Automatic After test, press C

No

Yes Button on meter Check strip Automatic marking

No Button on meter Automatic Before test, press C

Memory

100

250

2500

250 Profile 75 Basic 150 InTouch

Software

Win Glucofacts

FreeStyle Connect Data Management System

Languages Support Range (mg/dL) Strip expiration

Symbols 800-348-8100 10-600 Date on foil packet 10-40 (50-104°F)

Symbols 800-227-8862 20-600 3 months after opening vial 6-44 (43-111°F)

English 800-527-3339 20-600 Date on foil packet

Temperature range (°C) Humidity (%) Hematocrit (%)

5 888-522-5226 20-500 3 months after opening vial 10-35 (50-95°F)

InTouch Version FreeStyle Tracker Data Manage1.31 ment or FreeStyle CoPilot Web-based Management System 19 Profile 17 Basic 888-522-5226 800-227-8862 20-500 0-600 3 months after 4 months after opening vial opening vial 10-35 (50-95°F) 15-35 (59-95°F)

10-80 20-60

5-90 0-60

5-90 0-60

10-90 25-60

10-90 30-55

0-90 25-60

No Calibration bar Automatic Before test, insert test strip, hold button until marked 10 on meter; 125 on software Precision Link

18-30 (64-86°F)

SELF-MONITORING BLOOD GLUCOSE

Table 3 Self-monitoring Blood Glucose Software Monitor

Software

Software Locator

Roche Accu-Chek Products™

Accu-Chek Compass Diabetes Care Software; Accu-Chek Pocket Compass (for personal digital assistant)

Bayer Ascensia Products™

Ascensia Glucofacts Diabetes Management Software

BD Products™ LifeScan OneTouch Products™ MiniMed CGMS™ TheraSense FreeStyle Tracker™

BD Diabetes Software, Diabetes Software Simplified OneTouch Diabetes Management Software, OneTouch Diabetes Management v2.0 CGMS Solutions software FreeStyle Tracker Diabetes Management System; FreeStyle Tracker CoPilot Web Based System

TheraSense FreeStyle™

FreeStyle Connect Data Management System

http://www.accu-chek.com/products/main.cfm?pid= 4020; must purchase cable and software: http://www.accu-chek.com/products/main.cfm?pid= 4030; to purchase call 800-428-5076 http://www.bayercarediabetes.com/prodserv/products/ glucofacts/index.asp; free downloads available on Web site; cable adapter must be purchased http://www.bddiabetes.com/us/bgm/software.jsp; must purchase cable and software http://www.lifescan.com/products/otdms/index.html; free software downloads available on Web site Available to health care providers only; not for patient use http://www.therasense.com/tracker/download/index. asp\; http://www.therasense.com/freestylecopilot/; free software downloads available on Web site http://www.therasense.com/freestyle/datamanagement/ index.html; must purchase cable and software

Note: CGMS = continuous glucose monitoring system.

Tale 4 13,17-26 Blood Glucose Monitor Alternative Site Testing Comparison Monitor Accu-Chek Active™ Accu-Chek Compact™ Bayer Ascensia Dex™ Bayer Ascensia Elite XL™ Bayer Ascensia Breeze™ OneTouch Ultra™ TheraSense FreeStyle™

Finger

Forearm

Approved Approved Approved Approved Approved Approved Approved

Approved Approved Approved Approved Approved Approved Approved

Upper Arm

Thigh

Calf

Palm

Abdomen

Approved

Approved Approved Approved

Approved Approved Approved Approved

Approved Approved Approved Approved

Approved Approved Approved

Approved

Approved

Approved

Approved

patients to consult with their health care providers before choosing an alternative site for testing. The Food and Drug Administration mandates labeling unless there is no lag time between the glucose results between the finger and the alternative site.17-19,36-38 The recommendations are as follows: (1) Use the fingertip sample when (a) participating in risky activities or (b) if the patient has hypoglycemic unawareness. (2) Use alternative site testing only (avoid SMBG on alternative sites when there is a chance the blood glucose will change rapidly) when (a) fasting, (b) it is 2 hours after a meal, (c) it is more than 2 hours after taking medications, or (d) it is more than 2 hours after exercise. (3) Use an area of the skin that is free from hair and visible veins. (4) If the blood glucose results from the arm are not matching how the patient feels, then he or she should complete a subsequent finger test. (5) Have the patient rub the area for alternative site testing before completing the blood glucose test.18,23,32,36,37,40

Patients may be reluctant to use alternative site testing or may be unaware that their SMBG device has been approved for alternative site testing. Health care providers need to make certain patients are aware of when alternative site testing is inappropriate. Additionally, healthcare providers should demonstrate proper technique including how to obtain an adequate blood sample and to rub the testing area prior to use. TECHNOLOGY TRENDS AND ADVANCES The OneTouch UltraSmart™ is a meter and electronic logbook combined in one system. The UltraSmart™ uses the OneTouch™ test strips but provides the user with the option to track FastFacts™ such as exercise, medication (eg, oral and insulin medications), health checks, and food average. In addition, the UltraSmart™ provides the patient the opportunity to graph blood glucose results according to all the data, by JOURNAL OF PHARMACY PRACTICE 2004(17.1) •

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BRIGGS AND CORNELL meals, by time of day, and by exercise.25,41 TheraSense FreeStyle™ Tracker combines the usual blood glucose monitor with a handheld PDA, the Handspring Visor™. Within the FreeStyle Tracker base, there is a 2500 food list with serving sizes and carbohydrate values. The PDA software allows tracking of the carbohydrate intake, exercise, medication (including insulin) entry, and state of the patient’s health. Reports include statistics in graphs and charts shown on the PDA. These devices with state-of-the-art technology are not ideal for all patients. Elderly patients with dementia-related difficulties or those with diminished vision are not ideal candidates for these devices.31 Combination blood glucose monitor and insulin delivery is seen in the Novo Nordisk™ and OneTouch InDuo™ Monitor. The InDuo™ Monitor uses OneTouch™ test strips for SMBG, the Novo Nordisk PenFill insulin cartridges, and Novo Nordisk NovoFine™ needles for the insulin pen. The automatic display allows the patient to see the previous dose of insulin given and the time passed since delivery of the last dose.39 The BD Latitude Diabetes Management System™ is also an all-in-one combination, including removable lancet device, removable area for insulin pen, storage area for lancets and pen needles, and a blood glucose monitor. The monitor stores up to 250 test results and 250 insulin records. The BD Latitude™ provides an allin-one diabetes care device to allow patients to maintain organization with their glucose monitor and insulin supplies.42 CONTINUOUS GLUCOSE MONITORING SYSTEMS Even with advancements in technology in blood glucose meters, there has been continual research conducted to find more effective and efficient ways to record and track patients’ glycemic trends. The continuous glucose monitoring systems (CGMSs) provide useful information, such as continuous glucose readings over a specific interval of time, in order for health care providers to make sound clinical decisions concerning the patient’s diabetes care. It is important to educate patients and health care providers that CGMS is not designed to replace SMBG meters but to assist clinicians in making better therapeutic decisions by detecting trends in blood glucose levels.43 Available by prescription only, the MiniMed™ CGMS measures interstitial fluid glucose levels through a subcutaneous implanted sensor, which uses a glucose oxidase platinum electrode and the electrical current caused by the oxidation of glucose in the inter36 • JOURNAL OF PHARMACY PRACTICE 2004(17.1)

stitial fluid. The MiniMed™ CGMS needs to be calibrated by an SMBG test before use, after a 1-hour warmup period, and that reading is then entered into the CGMS unit. The MiniMed™ CGMS measures the glucose every 10 seconds, reports an average every 5 minutes, and collects data up to a 72-hour period (288 readings a day). The frequent reading allows for filling in of the gaps that are left behind by finger-stick glucose readings. The downloading capabilities allow the health care professional to make clinical judgments based on the results; however, the patient cannot see immediate results in “true time” as with traditional blood glucose meters. The patient can mark meals, medications, exercise, or events that occur during the 72-hour monitoring period to show correlation between glucose readings and activities, medications, and events. To ensure the accuracy of the data recorded, the patient must enter SMBG values into the unit at least 4 times per day. For clinicians to use CGMS in their patients, an extensive training session is required. Patients need to know how to program data and how to respond to sensor warnings.43 Interstitial fluid glucose levels are similar to fingerstick (capillary) measurements when blood glucose is not changing rapidly. The MiniMed™ CGMS boasts accurate glucose results, comparable to capillary blood glucose results.44-47 More studies are needed in larger populations to determine place in therapy and overall effectiveness. The MiniMed™ CGMS is to be used by health care providers to improve diagnostic capabilities and not for individual patient use. The MiniMed™ CGMS system may be useful in the following situations:43 (1) elevated A1C; (2) hypoglycemic episodes and unawareness; (3) hyperglycemic episodes; (4) diabetic ketoacidosis; (5) unexplained blood glucose excursions; (6) gastroparesis; (7) gestational diabetes, preconception, pregnancy, and nursing; (8) evaluation of therapeutic changes to medication regimen; (9) evaluation of behavioral modifications affecting glycemic control; and (10) patients undergoing erythropoietin therapy because A1C may be unreliable. The GlucoWatch™ Automatic Glucose Biographer G2 is the second generation of the glucose biographer. Available by prescription only, the glucose biographer, like the MiniMed™ CGMS, is not designed to replace SMBG meters but to assist clinicians in making better therapeutic decisions by detecting trends in blood glucose levels.48 The disposable automatic sensor device collects glucose into 2 gel discs through the skin by a small electronic current to measure glucose levels every 10 minutes. This process is called reverse iontophoresis. The autosensor collects data for 13 hours and must be replaced each time the patient wears the glu-

SELF-MONITORING BLOOD GLUCOSE

cose biographer. The glucose biographer records up to 6 values per hour and retains up to 8500 blood glucose values.49 The glucose biographer also needs to be calibrated by an SMBG test before use, however, after a 2-hour warm-up period. The SMBG value is then entered into the glucose biographer. Calibration adjusts the biographer for the skin site chosen. Unlike the MiniMed™ CGMS, the GlucoWatch™ provides readable glucose readings on the face of the device. Hyperglycemia and hypoglycemia levels are preset into the device, allowing the glucose biographer to alert the patients if these readings should occur. The manufacturer suggests setting the hypoglycemia levels at 10 to 20 mg/dL above the level at which hypoglycemia needs to be detected. Trend arrows point up or down when there is a > 9.0 mg/dL change in blood glucose since the last reading. A software package, the GlucoWatch™ Analyzer, is available to assist in determining results. The patient still needs to identify significant events that have occurred in the past 48 hours in a logbook.48 Many patients have experienced skin irritation or blisters associated with wearing the glucose biographer. To reduce these adverse events, it is recommended that the patient rotate sites where the biographer is placed, keep the skin clean and dry at all times, avoid scratching irritated skin, and keep lotion on irritated skin while the biographer is removed. Excessive sweating will cause the glucose biographer to shut off or skip a reading, causing the alarm to sound. The patient needs to know the signs and symptoms of hypoglycemia can include sweating.48 A review of 4 clinical studies revealed the glucose biographer readings lag behind blood glucose values by an average of 18 minutes; however, the multiple readings of the device provided a more accurate interpretation of patients’ glycemic control than the capillary finger-stick method. The device’s glucose values correlated with capillary blood glucose levels (r = .90, 1554 paired data points). The GlucoWatch™ was deemed to be both precise and accurate.49,50 Two types of tests should be completed on a regular basis. The system check to make sure the biographer is operating properly should be completed before the patient uses it for the first time and then completed once before using the first AutoSensor from a new box. This process is similar to the control solution checks completed with the SMBG meters. The quality control test should be conducted if the AutoSensors have been exposed to extreme temperature, if the patient is having difficulty calibrating the glucose biographer, or if there are questions concerning a series of the glucose biographer readings.48

Optical coherence tomography (OCT) is a newer technique for noninvasive blood glucose monitoring. The OCT uses an interferometer with a low light source, a mirror that moves over the arm, and a photodetector that measures the interferometric signal. A study of 426 blood samples and 8437 OCT images showed good correlation between OCT and venous samples’ blood glucose concentration. Another new novel noninvasive blood glucose monitor under study uses the infrared spectroscopy in the form of thermal emission spectroscopy. This prototype is a handheld device using similar technology seen in the tympanic membrane thermometers.51 Initial testing was done with the thermal emission spectroscopy in 23 patients and showed accurate glucose readings without the need for calibration. Further studies are needed to confirm these results; however, this shows one more step toward eliminating invasive SMBG.52 CONCLUSION Controlling hyperglycemia leads to slower onset and decreased severity of diabetes-related complications as proven by the DCCT and UKPDS.4,5 The first step toward tight glucose control is patient adherence to SMBG and taking charge of their disease. There are numerous barriers and sources for errors associated with SMBG. As pharmacists, we are in a unique position to provide knowledgeable information and education about SMBG technology to patients, the best time to test based on needs and medications, how to prevent errors, interpretation of the SMBG results, and assistance overcoming SMBG barriers. REFERENCES 1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2003;26:S5-S20. 2. National Diabetes Information Clearing House: A Service of National Institute of Diabetes and Digestive and Kidney Disease. National diabetes statistics. NIH Web site. Retrieved August 17, 2003, from http://diabetes.niddk.nih.gov/dm/pubs/statistics/. 3. American Diabetes Association Position Statement. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2003;26:S33-S50. 4. United Kingdom Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-853. 5. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.

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6. American Association of Clinical Endocrinologists. Diabetes guidelines. Endocr Pract. 2002;8(supp 1):41-65. 7. Weiner JP, Parente ST, Garnick DW, et al. Variation in office based quality. A claims-based profile of care provided to Medicare patients with diabetes. JAMA. 1995;273:1503-1508. 8. Glascow RE, Boles SM, Calder D, et al. Diabetes care practices in primary care: results from two samples and three measurement sets. Diabetes Educ. 1999;25:755-763. 9. American Diabetes Association. Testing of glycemia in diabetes. Diabetes Care. 2003;26:S106-S108. 10. Harris MI. Frequency of blood glucose monitoring in relation to glycemic control in patients with type 2 diabetes. Diabetes Care. 2001;24:979-982. 11. Franciosi M, Pellegrini F, De Berardis G, et al. The impact of blood glucose self-monitoring on metabolic control and quality of life in type 2 diabetic patients: an urgent need for better educational strategies. Diabetes Care. 2001;24:1870-1877. 12. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes. JAMA. 2002;287:360-372. 13. Cornell S. Self-monitoring blood glucose monitor update. Advances in Pharmacy. 2003;1:106-111. 14. Demers J, Kane MP, Bakst G, et al. Accuracy of home blood glucose monitors using forearm blood samples: FreeStyle versus OneTouch Ultra. Am J Health-Syst Pharm. 2003;60:1130-1135. 15. Nettles A. User error in blood glucose monitoring. Diabetes Care. 1993;16:946-948. 16. Skeie S, Thue G, Nerhus K, et al. Instruments for self-monitoring of blood glucose: comparisons of testing quality achieved by patients and a technician. Clin Chem. 2002;48:994-1003. 17. Ascensia Breeze™ Blood Glucose Monitoring System [user guide]. Mishawaka, IN: Bayer HealthCare LLC; 2003. 18. Ascensia Dex2™ Diabetes Care System [user guide]. Mishawaka, IN: Bayer HealthCare LLC; 2002. 19. Ascensia Elite XL™ Diabetes Care System [user guide]. Mishawaka, IN: Bayer HealthCare LLC; 2002. 20. OneTouch Ultra™ Blood Glucose Monitoring System [owner’s booklet]. Milpitas, CA: LifeScan, Inc; 2000. 21. Accu-Chek Advantage™ Blood Glucose Monitoring System [user’s manual]. Indianapolis, IN: Roche Diagnostics Corporation; 2001. 22. Accu-Chek Active™ Blood Glucose Monitoring System [user’s manual]. Indianapolis, IN: Roche Diagnostics Corporation; 2001. 23. Accu-Chek Compact™ Blood Glucose Monitoring System [user’s manual]. Indianapolis, IN: Roche Diagnostics Corporation; 2001. 24. Freestyle™ Blood Glucose Monitoring System [owner’s booklet]. Alameda, CA: TheraSense, Inc; 2002. 25. OneTouch UltraSmart™ Blood Glucose Monitoring System [owner’s booklet]. Milpitas, CA: LifeScan, Inc; 2002. 26. Accu-Chek Advantage™ Blood Glucose Monitoring System [owner’s booklet user’s manual]. Indianapolis, IN: Roche Diagnostics Corporation; 2001. 27. LifeScan, Inc. Frequently asked questions about alternative site testing. Life Scan report AW057-633. Milpitas, CA: LifeScan, Inc; 2002. 28. American Diabetes Association. Self-monitoring of blood glucose. Diabetes Care. 1994;18:81-86. 29. Adams AS, Mah C, Soumerai SB, et al. Barriers to self-monitoring of blood glucose among adults with diabetes in an HMO: a cross sectional study. BMC Health Serv Res. 2003;3:6. 30. Accu-Chek™. Products. Retrieved August 31, 2003, from http:// www.accu-chek.com/products/main.cfm. 31. TheraSense. FreeStyle Tracker™. Retrieved August 28, 2003, from http://www.therasense.com/tracker/index.asp.

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32. McGarraugh G, Price D, Schwartz S, Weinstein R. Physiological influences on off-finger glucose testing. Diabetes Technol Ther. 2001;3:367-373. 33. Berlin I, Bisserbe JC, Eiber R, et al. Phobic symptoms, particularly the fear of blood and injury, are associated with poor glycemic control in type 1 diabetic adults. Diabetes Care. 1997;20:176-178. 34. Lock JP, Szuts EZ, Malomo KJ, Anagnostopoulos A. Wholeblood glucose testing at alternative sites. Diabetes Care. 2002;25:337-341. 35. Jungheim K, Koschinsky T. Risky delay of hypoglycemia detection by glucose monitoring at the arm. Diabetes Care. 2001;24:1303-1304. 36. McGarrugh G. Response to Jungheim and Koschinsky. Diabetes Care. 2001;24:1304-1305. 37. Ellison JM, Stegmann JM, Colner SL, et al. Rapid changes in postprandial blood glucose produce concentration differences at finger, forearm, and thigh sampling sites. Diabetes Care. 2002;25:961-964. 38. Bennion N, Christensen NK, McGarraugh G. Alternative site glucose testing: a crossover design. Diabetes Technol Ther. 2002;4:25-33. 39. LifeScan, Inc. Abbreviated procedure guide. Life Scan report AW057-845A. Milpitas, CA: LifeScan, Inc; 2002. 40. Ginsberg BH. The FDA reevaluates alternative site testing for blood glucose. Diabetes Technol Ther. 2002;4:347-349. 41. LifeScan, Inc. Ease of use of the OneTouch UltraSmart Blood Glucose Monitoring System by patients with diabetes. LifeScan report AW058-875A. Milpitas, CA: LifeScan, Inc; 2003. 42. BD Latitude Diabetes Management System. Retrieved August 21, 2003, from http://www.bddiabetes.com/us/bgm/latitude_product.jsp. 43. MedTronic Minimed CGMS System Gold Product Information. Retrieved August 23, 2003, from http://www.minimed.com/ patientfam/pf_products_cgms_ov_completepic.shtml. 44. Gross TM, Bode BW, Einhorn D, et al. Performance evaluation of the MiniMed Continuous Glucose Monitoring System during patient home use. Diabetes Technol Ther. 2000;2:49-56. 45. Monsod TP, Flanagan DE, Rife F, et al. Do sensor glucose levels accurately predict plasma glucose concentrations during hypoglycemia and hyperinsulinemia? Diabetes Care. 2002;5:889-893. 46. Metzger M, Leibowitz G, Wainstein J, et al. Reproducibility of glucose measurements using the glucose sensor. Diabetes Care. 2002;25:1185-1191. 47. Chase HP, Kim LM, Owen SL, et al. Continue subcutaneous glucose monitoring in children with type 1 diabetes. Pediatrics. 2001;107:222-226. 48. The GlucoWatch G2 Automatic Glucose Biographer. Product information. Retrieved August 23, 2003, from http:// www.glucowatch.com/us/professional/index.html. 49. Potts RO, Tamada JA, Tierney MJ. Glucose monitoring by reverse iontophoresis. Diabetes Metab Res Rev. 2002;18(suppl 1):S49S53. 50. Garg SK, Potts RO, Ackerman NR, et al. Correlation of fingerstick blood glucose measurements with GlucoWatch Biographer glucose results in young subjects with type 1 diabetes. Diabetes Care. 1999;22:1708-1714. 51. Larin KV, Eledrisi MS, Motamedi M, et al. Noninvasive blood glucose monitoring with optical coherence tomography. Diabetes Care. 2002;25:2263-2267. 52. Malchoff CD, Shoukri K, Landau JL, et al. A novel noninvasive blood glucose monitor. Diabetes Care. 2002;25:2268-2275.