2020

THE ROLE OF BLOOD GLUCOSE MONITORING IN DIABETES MANAGEMENT

CONTRIBUTING AUTHORS RUTH S. WEINSTOCK, MD, PHD, FACE, FACP SUNY Distinguished Service Professor; Chief, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine; and Medical Director, Clinical Research Unit and Joslin Diabetes Center at Upstate Upstate Medical University Syracuse, NY

GRAZIA ALEPPO, MD, FACE, FACP Professor of Medicine Northwestern University Feinberg School of Medicine Chicago, IL

TIMOTHY S. BAILEY, MD, FACE, FACP, CPI President and Chief Executive Officer AMCR Institute Escondido, CA, and Clinical Associate Professor University of California San Diego School of Medicine San Diego, CA

RICHARD M. BERGENSTAL, MD Executive Director International Diabetes Center, Park Nicollet/ HealthPartners Minneapolis, MN

WILLIAM A. FISHER, PHD Distinguished Professor Emeritus and Adjunct Research Professor Department of Psychology, Western University London, Ontario, Canada

DEBORAH A. GREENWOOD, PHD, RN, BC-ADM, CDCES, FADCES President and Owner Deborah Greenwood Consulting Sacramento, CA

LAURA A. YOUNG, MD, PHD Associate Professor of Medicine and Director, Endocrinology Fellowship Program University of North Carolina School of Medicine Chapel Hill, NC

This publication has been supported by unrestricted educational grants to the American Diabetes Association from Ascensia and Lifescan. The Role of Blood Glucose Monitoring in Diabetes Management is published by the American Diabetes Association, 2451 Crystal Drive, Arlington, VA 22202. Contact: 1-800-DIABETES, professional.diabetes.org.

The opinions expressed are those of the authors and do not necessarily reflect those of Ascensia, Lifescan, or the American Diabetes Association. The content was developed by the authors and does not represent the policy or position of the American Diabetes Association, any of its boards or committees, or any of its journals or their editors or editorial boards.

© 2020 by American Diabetes Association. All rights reserved. None of the contents may be reproduced without the written permission of the American Diabetes Association. To request permission to reuse or reproduce any portion of this publication, please contact [email protected].

Cover image credits Front: Science Photo Library / Getty Images Back: Stockbyte / Getty Images Connected for Life.

Dear ADA Journal Subscriber:

I am pleased to present to you “The Role of Blood Glucose Monitoring in Diabetes Management,” the latest in the American Diabetes Association’s (ADA’s) Clinical Compendia Series. Produced by ADA and supported by unrestricted educational grants from Ascensia and Lifescan, this valuable resource reviews the continuing importance of blood glucose monitoring (BGM) in diabetes management, even in this age of rapid technological advancements.

In her introduction, lead author Ruth S. Weinstock, MD, PhD, FACE, FACP, of Upstate Medical University in Syracuse, NY, notes that, although home BGM revolutionized diabetes self-management four decades ago, the more recent advent of personal continuous glucose monitoring (CGM) systems has raised questions regarding its role moving forward. She and her team of expert co- authors then set out to answer those questions, explaining why BGM remains a useful and cost-effective source of glycemic data for many people with diabetes.

The authors review key issues related to the optimal use of BGM. They discuss the high level of accuracy of modern glucose meters and how that accuracy is measured, and they review current recommendations regarding the frequency and timing of BGM for people with different types of diabetes and therapeutic regimens. They offer specific strategies for making the best use of BGM to improve glycemic management and therapeutic outcomes, as well as tips for overcoming common barriers. They then position BGM in today’s high-tech diabetes landscape, describing the complementary uses of BGM and CGM, as well as the latest blood glucose–related innovations, including Cloud-based data management, mobile apps, insulin calculators, and remote and automated counseling systems. The authors conclude that BGM is, and will continue to be, an important tool in diabetes management, even as technologies continue to evolve.

Sincerely,

Robert A. Gabbay, MD, PhD Chief Scientific & Medical Officer American Diabetes Association

2451 Crystal Drive Suite 900 Arlington, VA 22202

1-800-DIABETES (342-2383) diabetes.org

@AmDiabetesAssn Ruth S. Weinstock, MD, PhD, THE ROLE OF FACE, FACP1 Grazia Aleppo, MD, FACE, FACP2 Timothy S. Bailey, MD, FACE, BLOOD GLUCOSE FACP, CPI3,4 Richard M. Bergenstal, MD5 MONITORING William A. Fisher, PhD6 Deborah A. Greenwood, PhD, RN, BC-ADM, CDCES, FADCES7 IN DIABETES 8 MANAGEMENT Laura A. Young, MD, PhD ABSTRACT | The introduction of home blood glucose monitoring (BGM) 40 years ago revolutionized diabetes self-management, providing valuable glucose data that have helped many people with diabetes (PWD) improve their glycemic management. In the early 2000s, personal continuous glucose monitoring (CGM) systems also became available, raising questions regarding the future role of BGM. However, for some PWD, particularly many with type 2 diabetes who do not take medications associated with increased hypoglycemia risk, BGM remains more easily accessible and more affordable than CGM and can adequately meet their needs. In addition, PWD who use CGM still need to periodically use BGM. This publication reviews key issues related to the optimal and most cost-effective use of BGM. The authors address the accuracy of modern glucose meters and the recommended frequency of monitoring for people with different types of diabetes and therapeutic regimens. They suggest strategies for using glycemic data to inform therapy adjustments, as well as ways to overcome common barriers to BGM use. They then review the use of BGM in patients who also use CGM and describe the latest related technological innovations, including Cloud-based data management, mobile applications, insulin calculators, and remote and automated counseling systems. The authors conclude 1Upstate Medical University, Syracuse, NY that BGM remains an important tool in diabetes management, even as 2Northwestern University Feinberg School diabetes management technologies continue to evolve. of Medicine, Chicago, IL 3AMCR Institute, Escondido, CA The introduction of home blood glucose monitoring (BGM) in the late 4University of California San Diego School 1970s and regulatory clearance of the first meter for this purpose in 1980 of Medicine, San Diego, CA revolutionized the self-care of people with diabetes (PWD) (1–3). Although 5International Diabetes Center, Park often referred to as “self-monitoring of blood (or plasma) glucose,” this form Nicollet/HealthPartners, Minneapolis, MN of glucose monitoring will be referred to by the more succinct “BGM” in 6Department of Psychology, Western this compendium. Knowing one’s current glucose reading and being able to University, London, Ontario, Canada 7Deborah Greenwood Consulting, examine and better understand glucose patterns enable PWD to adjust their Sacramento, CA food intake, activity, and medications to achieve their glycemic goals. 8University of North Carolina School of Over the past 40 years, glucose meters have become ever smaller, more Medicine, Chapel Hill, NC accurate, and more widely available (3). Today, they require less blood and Address correspondence to Ruth provide readings more rapidly, and the lancets used to perform fingersticks S. Weinstock, MD, PhD, FACE, cause less discomfort than ever before. BGM has provided valuable data FACP, [email protected] that have helped many PWD reach their glycemic targets.

In the early 2000s, personal continuous glucose monitoring (CGM) ©2020 by the American Diabetes devices became available and are now being used more commonly, especially Association, Inc. for PWD treated with intensive insulin therapy (3). The measures of accuracy, review the factors contributing increasing accessibility of CGM has raised questions to it, and discuss its impact on various stakeholders. regarding the future role of BGM in the management of diabetes. How Accuracy Is Measured For most PWD, CGM is more expensive than BGM. Accuracy is a concept comprising both trueness For PWD who do not require frequent daily glucose and precision. Trueness is defined as “closeness of monitoring to achieve their glycemic goals, partic- agreement between the average of an infinite number ularly those with type 2 diabetes who are not taking of replicate measured quantity values and a reference medications that commonly cause hypoglycemia, BGM quantity value,” whereas precision is defined as “close- remains more easily accessible and more affordable ness of agreement between indications or measured than CGM and, for many, can fulfill their glucose quantity values obtained by replicate measurements” self-monitoring needs. In addition, PWD who use CGM (6). A device with high degrees of both trueness and still need to periodically use BGM, as will be discussed. precision would be said to be highly accurate because In this monograph, we review issues that are it would likely produce individual results that would crucial to understand to ensure the optimal and most be consistently in close agreement with an accepted cost-effective use of BGM. These issues include the reference method. accuracy of available glucose meters; the recommended The error grid is a longstanding tool in the evaluation frequency of BGM for PWD who have different types of BGM accuracy. First developed by Clarke et al. (7), of diabetes and whose diabetes management follows it has subsequently been modified by Parkes et al. (8) different therapeutic approaches; strategies for using and others. In this approach, BGM results are plotted BGM to reach glycemic targets; barriers to BGM use against reference results, with grid regions defined to and ways to overcome them; the use of BGM in PWD reflect the potential risk severity of incorrect treatment who also use CGM; and technological innovations such triggered by the measurement error (Figure 1). Device as Cloud-based glucose data management systems, performance is typically reported as the percentage mobile applications (apps), insulin calculators, and of glucose values in lower-risk zone A or zones A and remote and automated counseling systems that incorporate BGM to improve care. B. Higher percentages indicate better performance. Overall, BGM remains an important tool for PWD, Because most current meters attain nearly 100% of even as diabetes management technologies continue results in these lower-risk zones, this method has to evolve. It is our hope that the information presented become less useful for comparing glucose meters. in this compendium will assist health care providers 550 (HCPs) in guiding their patients on the most appro- priate and cost-effective use of BGM. 500 E D C 450 B BGM ACCURACY 400 A Introduced in the 1970s (1,2), capillary BGM replaced 350 A urine glucose monitoring and in-office glucose 300 checking, which were neither timely nor actionable. 250 B Frequent BGM was the crucial intervention, along with 200 more frequent insulin dosing, of intensive treatment in the landmark Diabetes Control and Complications 150 C

Trial (4). Capillary glucose measurements gave people Measured Blood Glucose (mg/dL) 100 with diabetes and those caring for them data to under- 50 D stand variations in glucose levels, with the potential to 0 optimize basal and prandial insulin dosing. 050 100 150 200 250 300 350 400 450 500 550 Initial glucose meters were cumbersome and impre- Actual Blood Glucose (mg/dL) cise, and expectations were largely aspirational (5). However, over the years, both accuracy and usability FIGURE 1 Sample error grid. Reprinted with permission have greatly improved (3). Here, we describe the key from ref. 8.

2 The Role of Blood Glucose Monitoring in Diabetes Management Guidance from the U.S. Food and Drug Adminis- are performed under ideal laboratory conditions tration (FDA) and the International Organization for and thus may reflect only the analytical accuracy of Standardizations has been used to set minimum stan- the device. Most errors found in laboratory testing dards for regulatory clearance of glucose meters. These other than BGM have been reported to be either guidelines have become increasingly strict. In 2016, pre-analytical (46–68%) or post-analytical (18–47%). the FDA published criteria for meters for personal Indeed, only 7–13% of errors may occur during the use, stating that 95% of results should be within ±15% analytical phase (Table 1) (11). of the comparator method, and 99% of results should be within ±20% of the comparator across the entire Pre-Analytical Factors claimed measuring range (9). Devices for point-of-care Early meters required users to either blot or wipe professional use should achieve 95% of results within the glucose strip at a precise time interval. They also ±12% of the comparator method for blood glucose required the correct entry of a lot-specific test code. levels >75 mg/dL and within ±12 mg/dL for levels <75 Furthermore, both underfilling and overfilling the mg/dL; they should also achieve 98% of values within glucose strip could have altered test results. Fortu- ±15% of the comparator method for blood glucose levels nately, these potential sources of pre-analytical error >75 mg/dL and ±15 mg/dL for levels <75 mg/dL across have been mostly eliminated in newer meters by either the entire claimed measuring range (10). auto-correction or error detection. Testing within-run and intermediate precision is However, poor surface preparation of the capillary required to show that, among multiple meters and sampling site continues to contribute to pre-analytical glucose strip lots measuring a single sample, over time errors. Despite the known importance of cleansing the and with multiple devices, results are consistent. These site, many users are unaware of or neglect this step. Both results are best expressed as coefficient of variation, fruit handling (12) and the use of some body lotions which is calculated from mean and standard deviation (13) have been associated with pseudo-hyperglycemia. (SD). The effects of potential interfering substances Additionally, glucose strips damaged by inappropriate and other factors, such as hematocrit and altitude, are storage conditions and the dilutional effect of extra- expressed as bias (in mg/dL and percentages). neous fluid at the testing site have been associated with Accuracy data are reported to and reviewed by the pseudo-hypoglycemia (14). The impact of these factors FDA before a meter is cleared. However, there is no has increased because of the smaller sample volume post-marketing surveillance other than monitoring of required by newer meters. reported adverse events with use of the device. Thus, although technological advances have addressed many of the pre-analytical sources of reduced accuracy, Factors Contributing to Accuracy comprehensive patient education remains important to For a holistic understanding of accuracy, it is useful address remaining pre-analytical issues. to borrow terminology from laboratory science and separate glucose measurement errors into three Analytical Factors distinct categories: pre-analytical, analytical, and Glucose measuring technology has advanced in many post-analytical errors. Pre-analytical errors are those ways to meet the demand for greater accuracy. Glucose that occur before the device makes a measurement; oxidase has been the most important enzyme used to post-analytical errors are those happening after a measure glucose. However, as sensors changed from measurement is made. Many tests of meter accuracy optical to fully electrochemical, alternative enzymes

TABLE 1 Examples of Glucose Meter Measurement Errors

Pre-Analytical Analytical Post-Analytical • Poor skin surface preparation • Environmental (e.g., temperature, • Poor user numeracy • Use of incorrectly stored or humidity, altitude) • Misunderstanding because of incorrect expired test strips • Interfering substances (e.g., ascorbic glucose units (mg/dL vs. mmol/L) acid, acetaminophen, maltose) • Missing and fabricated glucose values • Degradation of manufacturers’ quality in manual log standards • Software processing errors

The Role of Blood Glucose Monitoring in Diabetes Management 3 have been used. Although these other enzymes have Canada) but who is accustomed to mg/dL units (e.g., generally improved performance, one—GDH-PQQ someone residing in the United States) might incor- (glucose dehydrogenase pyrroloquinoline quinone)— rectly interpret 10.0 mmol/L as 100 mg/dL (or vice led to harmful hypoglycemia resulting from inap- versa). Low numeracy has also been reported to be a propriate treatment of pseudo-hyperglycemia when barrier for some users (18). maltose, galactose, and xylose were detected nonspecif- The advent of meters that store a digital record of ically as glucose (15). glucose results confirmed the persistent suspicion Other potential sources of error that must be of many clinicians regarding logbooks (19): missing, assessed in glucose meters include altitude, hemato- phantom (“dry-lab”), and incorrectly transcribed read- crit, ascorbic acid, and acetaminophen. All devices ings are quite common. This problem persists today in must include results of these tests in their labeling. clinics where manual logbooks are still reviewed. In addition to better chemistry, advances in manu- In addition to missing, fabricated, and incorrectly facturing techniques, proper storage and distribution, recorded data, there is short- and long-term potential and quality processes to monitor these factors remain to underuse or even misuse BGM data. To address this crucial to ensuring accuracy. To date, there is no issue, structured BGM (20,21), described in more detail regulatory requirement that manufacturers of cleared on pages 6-7, has been proposed as a technique to make meters proactively demonstrate the continued accu- BGM data more actionable. A further development racy of their devices after initial clearance. has been meter connectivity, allowing BGM data to be The Diabetes Technology Society’s comparative transmitted via smartphone to the Cloud for enhanced study (16) evaluated 18 meters and glucose strips remote medication management. acquired through the retail channel in 1,032 subjects Innumerable mobile apps that can now accept BGM with a total of 5,584 data pairs. This study expanded data and provide insulin dosing advice represent an on previous studies (17) and evaluated all 18 meters additional source of post-analytical errors. Unfortu- at each of three research sites. During each of three nately, these apps vary considerable in quality (22). substudies, each site evaluated six meters. In each of They also require configuration by programming in a two subsequent studies, six additional meters were patient’s insulin-to-carbohydrate (I:C) ratio (the number tested in round-robin format such that each site verified of grams of consumed carbohydrate that 1 unit of insulin all meters. Only six of the 18 meters met accuracy will cover), insulin sensitivity factor (ISF; the blood standards (similar to, but slightly more lenient than, glucose lowering in mg/dL to be expected per unit of current regulatory standards) in all three substudies. insulin delivered), and duration of insulin action, and These data suggest that real-world meter performance often sophisticated input from users (e.g., carbohydrate may frequently differ from that initially reported by counting). These apps, and other BGM-related innova- manufacturers and support the need for post-marketing tions, are discussed in more detail starting on p. 18. surveillance to ensure reliable meter accuracy.

Post-Analytical Factors Why Accuracy Matters and to Whom Visual inspection and comparison of a result with a Although it may seem intuitively obvious that more color chart was commonplace with early meters, and accurate BGM is advantageous, access to any means this practice limited accuracy. Essentially all glucose of BGM is such a formidable barrier in low-resource meters now display data digitally to users, but despite settings (23) that a broader perspective is needed. Type this greater clarity, there remain several situations in 1 diabetes, pregnancy, and use of a CGM device that which the device user may inaccurately interpret the benefits from calibration are all compelling examples of result presented. For example, depending on locale, circumstances requiring high BGM accuracy. However, meters present data in either mg/dL or mmol/L. In people with type 2 diabetes who are not taking medica- the past, users could change the measurement units tions likely to cause hypoglycemia may accrue benefit (although, occasionally, device settings unpredictably even from less-expensive devices with lower accuracy changed). Manufacturers no longer allow users to ratings. In recognition of this, one major manufacturer change data units, but someone using a meter that of meters introduced a semi-quantitative system using displays results in mmol/L (e.g., a meter acquired in a smartphone camera (24). This approach allows a

4 The Role of Blood Glucose Monitoring in Diabetes Management mobile app to photograph a glucose strip and provide majority of PWD who do not yet use AID systems to an estimated glucose level range, rather than a specific manage glycemia. In the section starting on p. 18, we value, and does not require users to purchase a meter. will discuss in more detail how technology (e.g., apps, Likewise, a study of a meter that displayed color-coded expert systems, and bolus calculators) can make BGM glucose range data (in addition to a glucose value) data more actionable and reliance on such information demonstrated a salutary effect, particularly in people safer and more effective. with low numeracy (25). For PWD, meter accuracy affects not only insulin RECOMMENDATIONS FOR dosing decisions, but also confidence in their meter. For BGM USE example, if glucose is checked multiple times within a BGM via capillary blood historically has been consid- short interval and the results differ, trust in the meter ered a cornerstone of diabetes self-care. Touted as a may decline. Additionally, accurate BGM is required for key part of patients’ daily routine, when performed calibration of some CGM systems and is also needed for regularly, it can guide insulin dosing and help patients confirmation of CGM results or as a backup for people judge whether their noninsulin medications and who use a CGM system. Table 2 summarizes groups of lifestyle changes are having favorable effects. When the PWD who would benefit from greater BGM accuracy (26). desired results are not achieved, BGM values can be used by PWD and their care team to guide medication TABLE 2 PWD Requiring the Highest Possible Level of adjustments and further lifestyle modifications. BGM Accuracy Over the past several decades, BGM technology has PWD for whom BGM accuracy is particularly important evolved, making routine checking more affordable and include those who: accessible, and many providers universally recommend • Have a history of severe hypoglycemia or hypoglycemia daily BGM for all PWD. However, with the advent of unawareness newer noninsulin therapeutics that do not cause hypo- • Use a CGM device that benefits from calibration glycemia and the recognition that daily BGM may be • Are pregnant of little value in people with optimally managed type 2 • Receive insulin therapy diabetes has come a push to adopt a selective approach • Are otherwise at risk for hypoglycemia, such as those on an insulin secretagogue therapy (e.g., sulfonylurea or to BGM in people with diabetes. In the following meglitinide) sections, we discuss current recommendations for • Have occupations that enhance possible risks from BGM in people living with diabetes (26,29), which are hypoglycemia (e.g., requiring driving or operating also summarized in Table 3. hazardous machinery) One way to determine who might benefit most from Adapted from ref. 26. routine BGM is to consider individual patient factors such as insulin use, pregnancy, hypoglycemia history, Few prospective data directly address meter hypoglycemia unawareness, and blood glucose levels accuracy and health economics outcomes. Although it that are difficult to normalize. Although our intent is would be unethical to randomize study participants to to convey best practices supported by high-quality a less accurate meter, such questions can be and have data, it is important to recognize that, in many cases, been posed through simulations. Cost savings have there is no one correct answer and that a personalized been modeled to occur with more accurate meters in approach to BGM is recommended. people with type 1 or insulin-treated type 2 diabetes. These savings were primarily driven by reductions in People with Type 1 Diabetes hypoglycemia and hospitalization, with a much smaller Although the use of CGM is increasing, some people measured contribution from reduction of long-term living with type 1 diabetes will choose to continue with complications (27,28). daily BGM exclusively. Reasons some patients may Accuracy alone is not enough to improve health decide to continue to use BGM include higher costs of outcomes of PWD. Accurate, actionable glucose CGM systems, unacceptability of being connected to a data must be communicated to automated insulin device, and overload with regard to the quantity of data delivery (AID) systems when used, clinicians, and the CGM provides (30).

The Role of Blood Glucose Monitoring in Diabetes Management 5 TABLE 3 BGM Frequency by Type of Diabetes and Treatment Regimen: General Recommendations

Treatment Type 1 Type 2 Regimen Diabetes Diabetes GDM Regimens N/A For most PWD, BGM is not recommended. 4 times/day until optimal without insulin, Consider using it, though, when altering glycemic control is achieved, sulfonylurea, or treatment, symptoms of hyperglycemia develop, then 1–2 times/day meglitinide or acute illness occurs; in some instances, intermittent use can assist with self-management. Regimens with N/A Recommended as needed to detect, treat, and 4 times/day until optimal sulfonylurea, prevent hypoglycemia; when symptoms of glycemic control is achieved, meglitinide, or hyperglycemia develop; or when acute illness then 1–2 times/day basal insulin occurs. Consider also when altering treatment or when A1C is above goal. For some PWD, intermittent use can assist with self-management. Generally recommended 0–3 times/day Basal-bolus insulin 4–10 times/day Up to 6–10 times/day 4–10 times/day regimen These recommendations are based on published guidelines and the expert opinion and clinical experience of the authors. NA, not applicable.

Given the day-to-day glycemic variability that on occasion to confirm extreme hyperglycemia or people with type 1 diabetes typically experience, hypoglycemia measured via CGM or when they suspect recommended BGM frequency per day will vary by CGM sensor or transmitter malfunction. person and anticipated daily activities. At a minimum, it is recommended that people with type 1 diabetes People with Type 2 Diabetes who are not using CGM perform BGM 4 times/day Those Who Do Not Use Insulin (before meals and at bedtime). Other times people with The role of BGM for people with type 2 diabetes who type 1 diabetes should check their blood glucose level are not using insulin is one of the more contested issues include before exercise, during prolonged exercise, in diabetes management. Some previous trials have occasionally after meals, and whenever they have signs shown benefit of BGM on glycemic outcomes (31–34), or symptoms of hypoglycemia. For people who have whereas others have shown no such benefit (35–38) in hypoglycemia unawareness, performing BGM before this population. activities that require clear cognition (e.g., driving, Of the studies that have shown benefit, using a caring for children, or operating heavy machinery) structured approach and ensuring that both PWD should be the norm. More frequent BGM is also needed and providers review the results has proven to be the during acute illness or times of stress. Thus, for most most efficacious strategy. Examples of structured people with type 1 diabetes who are not using CGM, approaches include paired checking and intermittent, performing BGM 4–10 times/day as needed is recom- frequent checking over a period of several days before mended. It is essential, however, to recognize the need a clinical visit (39). These studies have been rigorous, to personalize this recommendation for each person controlled clinical trials with close participant based on the presence of complications and variability follow-up; thus, the beneficial results may be difficult to in daily life. realize in busy, real-world clinical practice settings. Another situation in which people with type 1 Although BGM may increase patients’ awareness diabetes must perform BGM is to calibrate certain of glucose values, which can support heathy lifestyle CGM systems. Although newer systems do not require choices, it is also important to consider the burden such calibration, some people still may be using older that BGM places on PWD. In large meta-analyses of CGM models that do or the Medtronic 670G system BGM in people with type 2 diabetes who were not using with the Guardian sensor, which also requires BGM insulin, a benefit of BGM on glycemic management calibration a minimum of twice daily. Additionally, was found in the short term (≤6 months), but when PWD who are using CGM may need to perform BGM assessed after 1 year of routine BGM, that benefit was

6 The Role of Blood Glucose Monitoring in Diabetes Management no longer significant (40–42). A recent large, pragmatic Women with Gestational Diabetes trial of PWD who were not using insulin and had A1Cs BGM has proven efficacy in women with gestational that reflected moderate to ideal glycemic management diabetes mellitus (GDM). Most approaches include demonstrated that, in a real-world setting, once-daily asking pregnant women at the time of GDM diagnosis to BGM did not improve glycemic outcomes or quality perform BGM several times daily to establish patterns of life compared to no BGM throughout an entire of hyperglycemia. Such women are often asked to year (43). perform BGM initially at least 4 times/day, including Increasingly, national organizations are encouraging in the morning while fasting and 1–2 hours after meals. providers and PWD to rethink the need for routine From these data, providers can identify women who BGM in people with type 2 diabetes who are meeting require pharmacologic therapy. or near their A1C targets when using medications that BGM values paired with food diaries can also do not cause hypoglycemia. It is still reasonable to guide dietary change recommendations, which are encourage people with type 2 diabetes who are expe- foundational to the treatment of GDM. Once glycemia riencing hypoglycemia or severe hyperglycemia, using is optimally managed, it is reasonable to decrease the therapies within the sulfonylurea and meglitinide frequency of BGM. This recommendation is based on classes, acutely ill, using steroids, or far from meeting trial data showing that women who performed BGM their glycemic targets to perform BGM, as discussed in 4 times/day had babies with similar birth weights and the next section, until optimal glycemic management a similar incidence of macrosomia as women who has been attained. Regardless of the views of specific carried out BGM once every other day. providers and PWD on this issue, BGM is only truly In summary, although CGM is gaining in popularity valuable to PWD when they are provided feedback on among all people with diabetes, BGM will remain the meaning of the values they obtain and guidance on an important component of diabetes self-care for how to make health behavior changes when needed. many people. The engagement of both PWD and their Those Who Use Insulin diabetes care team in interpreting and acting on blood For people with type 2 diabetes who require basal glucose data is crucial in all cases for BGM to be of insulin, BGM is recommended during basal dose optimal value. titration and at any time when hypoglycemia is a concern. During dose titration, blood glucose values USING BGM DATA TO ACHIEVE should be monitored in the morning while fasting and TREATMENT GOALS again at bedtime. Because newer basal insulin formulations lead to For BGM to make a meaningful difference in diabetes less glucose variability, the frequency of BGM may self-management, both PWD and their diabetes be reduced when a stable dose of basal insulin has care team must have the skills, understanding, been determined. However, people using basal insulin and ability to change health behaviors and adjust should always have a meter and glucose strips available pharmacologic therapies in response to glucose data given the potential for hypoglycemia. If a person’s (29,44,45). Focusing on BGM data is particularly fasting glucose is within target range but the A1C value important when glucose goals are not being met; for is still above goal, BGM before and after meals should people who are using insulin therapy or starting or be considered to check for postprandial hyperglycemia. titrating glucose-lowering medications; for tracking For most people with type 2 diabetes using a adverse events; when changes are being made to the basal-bolus regimen, BGM should occur at least 4 care regimen (including eating pattern and physical times/day, similar to people with type 1 diabetes. activity); when a new condition, change in condition, or instability develops; or during times of illness or stress People with Prediabetes (46,47). Table 4 identifies specific opportunities for In general, routine BGM is not recommended for learning from BGM data collected at different times of people who have prediabetes. Although the postulated day (29,47,48). Additionally, PWD can be taught that benefits of performing paired checking to assess the BGM is a great tool for making insulin dose decisions, impact of certain foods on glycemic excursions are determining their potential risk for or the presence intriguing, well-designed clinical trials are lacking. of hypoglycemia, getting feedback with regard to the

The Role of Blood Glucose Monitoring in Diabetes Management 7 glycemic consequences of their eating and physical TABLE 4 Information PWD and Their Diabetes Care Providers Can Learn from BGM Performed at Different activity choices, or whenever they might feel “off.” Times of Day (29,47,48) As previously noted, a structured approach to BGM Time of How Can the Data Be Used? has been shown to improve outcomes (39,49). This BGM approach, also called “structured testing” or “struc- Fasting • Determine the effect of the evening tured checking,” can be individualized by implementing medication different checking “profiles.” Examples of these profiles • Evaluate and titrate the basal insulin dose are described in Table 5 (50). The design of the profile • Determine the effect of physical activity (from the previous afternoon/evening) can be determined based on the desire to collect • If above goal, evaluate for: specific mealtime data (e.g., checking before and after • Dawn phenomenon the largest meal of the day) or in an exploratory nature • Rebound from nocturnal hypoglycemia to understand overall glycemic patterns. The struc- • Impact of evening meal/snacks, including late-night food intake tured data then create an opportunity for informed Before • Assess basal insulin dose requirements decision-making. meals After • Assess mealtime insulin dose requirements Pattern Management meals • Assess proper timing of insulin Understanding pattern management is the key to administration effective BGM (47). Searching for patterns in blood • Identify the need for additional medications glucose data is like being a detective trying to finding to target postprandial hyperglycemia clues that reveal trends and thereby identify oppor- • Assess the effectiveness of changes in the amount and composition of meals and tunities to improve glycemic management. There are snacks and/or physical activity in moving three factors to consider when engaging in pattern blood glucose into the target range management: 1) recognition that BGM will identify Bedtime • Assess the impact of pre-dinner medication the effects of food choices, physical activity, stress, and • Assess the impact of dinner and evening medications on daily glucose values; 2) PWD and their snacks and late afternoon/evening exercise diabetes care providers both need education on how 2:00 a.m. • Identify overnight hypoglycemia to interpret individual glucose values and patterns to

TABLE 5 Examples of BGM Structured Checking Profiles Profile Example Description Paired checking BB AB BL AL BD AD BT • Checking glucose before and after the M • • same meal for 7 days in a row T • • W • • • Used to evaluate the change in glucose Th • • levels from pre- to post-meal F • • Sa • • Su • • 7-Point profile BB AB BL AL BD AD BT • Checking glucose 7 times/day, for 3 days M • • • • • • • in a row T • • • • • • • W • • • • • • • • Provides an overall picture of glucose Th values before a clinic visit F Sa Su Staggered profile BB AB BL AL BD AD BT • Checking glucose before and after one M • • meal per day T • • W • • • Staggering the mealtimes provides more Th • data and a clearer picture of glucose F • levels and patterns Sa Su AB, after breakfast; AD, after dinner; AL, after lunch; BB, before breakfast; BD, before dinner; BL, before lunch; BT, bedtime.

8 The Role of Blood Glucose Monitoring in Diabetes Management TABLE 6 Three-Step Process for Evaluating BGM Data and Sample Questions to Help Identify Opportunities for Improvement Step 3: Step 1: Step 2: Collaborate to Individualize Issues to Explore Obtain 3–4 Days of Data Identify Patterns Diabetes Care and Education Healthy coping Are life stressors affecting Is the person stress-eating? What new techniques might self-care? the person try to reduce stress levels?

Healthy eating Is the person counting Are meal and snack portion Can changes be made to the carbohydrates? sizes consistent? amount of carbohydrate at mealtimes? Snacks?

Physical activity Is physical activity Is physical activity irregular? Can physical activity be documented (time of day, planned and more regular? intensity, duration, and type)?

Medication-taking Are medications taken as Is the diabetes medication Could a different type or dose prescribed? adequately covering of medication be taken? glucose peaks after meals?

BGM Is more BGM needed? Are BGM strips expired? Can the pattern of BGM be negotiated?

Problem-solving Have there been lifestyle Have you observed meter What changes is the person changes? use? willing to make?

Risk reduction If hypoglycemia is noted, Are medications expired? Could the treatment regimen what is the usual treatment? be simplified?

Adapted from ref. 47. inform adjustments to therapies or lifestyle behaviors; conversations with PWD can help to identify a glucose and 3) tools such as paper logbooks or digital apps are profile that will best reveal trends in various situations. needed to collect, analyze, and interpret data (47). Searching for patterns requires BGM values collected Many glucose meters come with their own apps that at the same time of day for a minimum of 3–4 days. One synchronize directly with the device, allowing users to framework for interpreting BGM data (47) sets out a log events (e.g., carbohydrate intake, physical activity, simple three-step process: 1) obtain at least 3–4 days and insulin doses) along with BGM data. of data, 2) identify patterns, and 3) collaborate with Living with diabetes 24/7, year in and year the PWD to individualize diabetes care and education out, is challenging. Understanding the value of based on the data collected (Table 6). pattern management can help PWD take charge of When reviewing BGM data, certain patterns should their self-management and play an active role in be given higher priority than others. First, focus on decision-making regarding their diabetes treatment. episodes of hypoglycemia. After hypoglycemia has Understanding their own BGM data can motivate resolved, review glucose values that are above the target them to make healthier choices and build their range. When post-meal glucose values are rising above self-confidence. Working with a certified diabetes target range, consider whether changes to both medica- care and education specialist to learn about BGM tion and health behaviors may be needed. When focusing and pattern management is important at the time of on health behaviors, review food portions, carbohydrate diagnosis and annually thereafter, as well as whenever counting, and the quality of food consumed. there is a change in medication or their condition or The following case studies describe different when glycemic goals are not being met (51,52). structured checking profiles and how BGM data can be Early clues from random BGM values or reviewed to make health and treatment decisions.

The Role of Blood Glucose Monitoring in Diabetes Management 9 What do you suggest? CASE 1: M.V. These BGM data suggest that M.V. needs more medica- M.V. is a 50-year-old woman with type 2 diabetes tion to manage her post-meal glucose excursions. Using for 11 years, who is taking metformin 1,000 mg twice a shared decision-making approach, you can discuss daily and glipizide 10 mg before breakfast and dinner. Her BMI is 25 kg/m2, her most recent A1C was 8.5%, the pros and cons of appropriate medication options and she notes feeling tired most of the time. She has with her and arrive at a plan. not been checking her glucose. After discussion, she agrees to perform a 7-point profile for 3 days before her next clinic visit so you CASE 2: K.B. can get a better idea of her glucose levels throughout K.B. is a 67-year-old woman who has lived with type the day. The data she shares at her next appointment 2 diabetes for 14 years. She is taking metformin 1,000 are displayed in Table 7. mg/day and 24 units of insulin glargine, which she reports taking every night at her 9:00 p.m. bedtime. Her BMI is 32 kg/m2. TABLE 7 Case 1: 3-Day, 7-Point Glucose Profile (mg/dL) She has been checking her fasting glucose levels several times per week, and all of her values have M.V.’s glycemic targets are 80–130 mg/dL before meals been <130 mg/dL. However, her A1C continues to and <180 mg/dL 2 hours after meals. be above goal and is currently 8.3%. She has never BB AB BL AL BD AD BT checked her glucose at other times of the day. Monday 125 201 150 256 129 259 203 You ask her about her meals and activity and learn Tuesday 130 249 174 241 122 263 214 that her biggest meal of the day is at dinner. Together, you decide that K.B. will take a “paired checking” Wednesday 129 223 142 203 126 281 199 structured approach to BGM, checking her glucose Thursday before and 2 hours after dinner nightly for 1 week and Friday then return for a follow-up appointment. Her BGM Saturday data are displayed in Table 8. Sunday

AB, after breakfast; AD, after dinner; AL, after lunch; BB, before breakfast; BD, before dinner; BL, before lunch; BT, bedtime. TABLE 8 Case 2: 1 Week of Paired Checking Glucose Values Before and 2 Hours After Dinner (mg/dL)

What questions do you ask? K.B.’s glycemic targets are 80–130 mg/dL before meals Start by asking M.V. what she notices and what infor- and <180 mg/dL 2 hours after meals. mation she can share with you. Solicit her opinion BB AB BL AL BD AD BT regarding what is working and what she believes may Monday 131 255 Tuesday 128 181 need to change. Ask her about her food choices and Wednesday 125 281 portion sizes and about her physical activity. Thursday 129 263 M.V. states that she is taking her medication as Friday 122 281 directed. She says she is unable to walk after breakfast Saturday 118 259 or lunch because of work and that she does not feel the Sunday 134 277 need to change her eating habits. AB, after breakfast; AD, after dinner; AL, after lunch; BB, before breakfast; BD, before dinner; BL, before lunch; BT, bedtime. What patterns do you see? M.V.’s pre-breakfast values are all within her target What questions do you ask? range. However, her post-meal values are above range, What does K.B. notice about her glucose values? Ask as are those at bedtime. The only times during the day her about her food choices and portion sizes at dinner. that she is in the target range are before breakfast and K.B. says she has been using an online weight loss before dinner. program and has been focusing on using the plate You learn that M.V. takes a walk every day 3 hours method at mealtimes. Although she does eat pasta and after lunch, which lowers her pre-dinner glucose level other carbohydrate-containing foods, she says her into the target range. portion sizes are small.

10 The Role of Blood Glucose Monitoring in Diabetes Management What patterns do you see? P.R. states that he typically eats a late breakfast and All of K.B.’s post-dinner glucose values are above her often has a small lunch. He likes to garden, and he target of <180 mg/dL. typically does that in the afternoon, often after lunch. His lunch is frequently just a handful of nuts, some What do you suggest? berries and a diet coke. He has been on a fixed dose of K.B. needs more medication to manage her post-meal prandial insulin for the past several years, but he says glucose excursions. Together, you consider adding a his appetite has changed lately. glucagon-like peptide-1 receptor agonist to her regimen You also ask what type of symptoms he has when to assist with both weight loss and glycemic manage- his glucose values drop to <70 mg/dL and how he ment. You might also suggest that K.B. use BGM to treats his low glucose. P.R. says that he usually feels check before and after other meals to see if her glucose sweaty and hungry, and then he feels shaky and levels are consistently out of range at any other times. lightheaded. He prefers to drink juice and keeps juice boxes in the refrigerator.

CASE 3: P.R. What patterns do you see? P.R. is an 80-year-old man who has been living with The first pattern you address is the two episodes of type 2 diabetes for 26 years. His A1C is typically hypoglycemia after lunch on Wednesday and Sunday. in range, at <7.0%. He has been taking 36 units of insulin degludec at bedtime and 8 units of rapid- What do you suggest? acting insulin before each meal. He states that he has been “feeling low” during the day. P.R. should reduce his pre-meal insulin dose at lunch. Together you discuss whether he would be willing to Sometimes he checks his glucose, but other times, he just drinks juice or eats a snack without checking. He adjust his pre-meal insulin doses based on the size of performs BGM infrequently, but when he does, it is the meal he is going to eat and his anticipated physical typically before breakfast and before bed. activity. You also ask if he would be willing to check his He agrees to your request that he check his glucose glucose before and after lunch to help identify the best before and after 1 meal/day for 1 week, alternating insulin dose for him at that meal. meals, as well as whenever he feels as if his glucose You refer P.R. to a diabetes care and education is low. The BGM results he brings to his follow-up visit are displayed in Table 9. specialist to review carbohydrate counting and portion sizes and to review BGM to develop a plan for insulin management. Using CGM could also be considered. TABLE 9 Case 3: 1 Week of Staggered Profile BGM Data (mg/dL) Solution-Focused Questioning P.R.’s glycemic targets are 80–130 mg/dL before meals Assessment of blood glucose management requires and <180 mg/dL 2 hours after meals. frequent discussions with PWD. A questioning BB AB BL AL BD AD BT approach is commonly used. Often, questions can Monday 105 144 make PWD feel blamed or shamed for out-of-range Tuesday 128 86 glucose values, elevated A1C levels, or decisions they Wednesday 58 125 104 have made, and this perceived negativity can seem Thursday 122 133 to devalue the hard work of living with a chronic Friday 118 99 condition. One alternative is to consider a more Saturday 132 167 solution-focused approach (53). Sunday 61 In this type of approach, questions focus on AB, after breakfast; AD, after dinner; AL, after lunch; BB, before what is going well for the person and are chosen to breakfast; BD, before dinner; BL, before lunch; BT, bedtime. identify existing strengths. For example, instead of asking about breakfast glucose values by saying, What questions do you ask? “Why are your after-breakfast numbers so high?” What does P.R. notice about his glucose values? Was consider asking, “Can you share with me an example this week typical for him, including the food he ate and of your typical breakfast?” From there, you can have his physical activity? a conversation based on the data. If the person is

The Role of Blood Glucose Monitoring in Diabetes Management 11 eating a high-carbohydrate breakfast, you might ask, BGM Is Behavior “What changes would you be willing to consider to To help PWD overcome barriers to BGM, it is essential bring your after-breakfast glucose levels into the to understand that BGM is behavior. As such, it is target range?” influenced by individuals’ store of actionable BGM Another strategy would be to focus on a time of the information, motivation to act on this information, day when glucose values are in range and ask questions and behavioral skills for acting on it effectively. Data about those times, again to identify strengths. For collected by carrying out BGM as recommended can example, “I see your before-dinner numbers are within serve as the basis for self-management actions that your target range most of the time. How did you achieve result in improved diabetes health outcomes, contrib- that?” With this type of question, you are strengthening uting to a virtuous feedback loop (Figure 2). your relationship with the person by building trust The impact of BGM information and motivation will and acceptance. This method also helps PWD identify often be limited by a person’s BGM behavioral skills. their own strengths and what is working well for them. Moderating factors such health literacy and ability In theory, this approach will help PWD do more of the to acquire and pay for supplies to check glucose may things that are working well for them and less of those influence the amount of BGM data collected, a person’s that are not working well (54). motivation and ability to carry out BGM with the recom- In summary, a structured approach to BGM can help mended frequency, and, ultimately, health outcomes. PWD and their diabetes care team accurately interpret Information and BGM glucose data, recognize patterns, and work together PWD may have information deficits that interfere with to make informed treatment decisions to improve BGM (57). Some may believe that their body can “feel” diabetes management. when their blood glucose is within their target range; some may not be aware of glucose checking patterns OVERCOMING BARRIERS TO BGM that can provide meaningful information; and others may believe that their A1C results tell them everything It is well established that BGM can serve as a basis for they need to know to manage their diabetes. self-management that is effective in achieving and main- taining positive glycemic outcomes (55,56). However, it Motivation and BGM is also well established that PWD do not always perform Personal and social motivation can also influence BGM as recommended and that those who do may not BGM (57). Personal motivation for BGM rests on a take appropriate self-management actions based on person’s perception of the overall costs and benefits their blood glucose data. In the previous section, we of BGM. PWD who believe that BGM has important focused on ways to assist PWD in making optimal use of payoffs will be inclined to carry out monitoring as BGM to achieve their treatment goals. Here, we look at recommended, whereas those who believe that BGM how to overcome the numerous barriers that may hinder has costs that outweigh the benefits are not as likely a person’s success in that endeavor. to consistently carry out BGM. Social motivation for

Moderating Factors Insurance, Burden of Illness, Provider Support, etc. BGM Information Diabetes BGM Behavioral BGM Diabetes Self-Management Skills Adherence Health Outcomes Action BGM Motivation

FIGURE 2 An Information—Motivation—Behavioral Skills model of BGM. Adapted from ref. 57.

12 The Role of Blood Glucose Monitoring in Diabetes Management BGM rests on a person’s perception that significant change—may all be effective in increasing a person’s others—spouses, children, diabetes care and education frequency of BGM and changing patterns of checking specialists—support their BGM efforts and endorse glucose (55,58,59). In the realistic context of the busy their interest in engaging in shared decision-making. and resource-limited clinical practice setting, means Thus, a supportive partner, or an indifferent physician, for assisting PWD in overcoming barriers to BGM must can influence BGM performance. be both brief and effective and must focus on those with Personal and social motivation to carry out BGM the greatest need. are often in competition with the impetus to engage in other activities that are incompatible with strictly Triage the Need for BGM Coaching following BGM recommendations. Many, if not most, BGM counseling should target individuals who are PWD will regard BGM as having important benefits experiencing difficulties in achieving their glycemic and social support, but sometimes less important goals. Such difficulties can involve inadequate or benefits and less social support than other aspects of uninformative testing, inability to translate results into their lives (e.g., maintaining concentration at work or self-management actions, or the need to change the enjoying a meal with friends). therapeutic regimen.

Behavioral Skills and BGM Follow Principles of Effective BGM Counseling Performing BGM as recommended places substantial Principles of efficient and effective BGM counseling behavioral skills demands on PWD (57). In the context are inspired by the procedures of and evidence base of busy day-to-day life, simply remembering to perform supporting Motivational Interviewing (59,60). For BGM at meaningful intervals may be a challenge. people identified as potentially benefiting from Financing supplies to check glucose within complex, improved BGM practices, the following counseling changing, or limited insurance coverage poses addi- approaches may prove helpful. tional challenges. Maintaining access to such supplies Acknowledge the Challenge when needed and discreetly, painlessly, and effectively Many PWD are defensive and fearful of provider censure lancing one’s finger or positioning a sensor, can also for variable performance of BGM. Legitimizing an be challenging. Still other behavioral skills demands individual’s struggle with the demands of BGM can be involve knowing how to talk to a busy HCP about prob- the first step in improving its practice. Consider asking, lems with BGM or interpreting and using its results. “Almost all of my patients find BGM to be a challenge. Moderating Factors and BGM How is it going for you?” Personal characteristics of PWD and their environ- View PWD as the Experts ment can have direct and indirect impacts on BGM Although clinicians are the experts in diabetes medical (57). These factors include inadequate insurance management, PWD are the experts in what would have coverage, limited health literacy, burden of disease to happen to improve their BGM. Change strategies that associated with diabetes (e.g., impaired eyesight, originate with PWD—as opposed to those proposed by impaired dexterity, and overall medication burden), clinicians—are often much better suited to individuals’ and comorbid conditions. Overall, optimal BGM will situations and therefore more likely to be adopted be achieved by well-informed, engaged, behaviorally (59,60). Motivational Interviewing–inspired questions skilled PWD and will be maintained when they experi- such as the following can be helpful in eliciting change ence positive health outcomes. strategies from PWD. Assisting Patients in Overcoming • “Can you help me understand what BGM is Obstacles to BGM like for you?” Optimal BGM needs to be taught, rehearsed, refined, • “On a scale of 1 to 10, how important is it for you to and reinforced by well-informed, well-motivated, and stick to the BGM pattern we’ve discussed?” Most behaviorally skilled clinician educators. A diversity people will respond with a high number. Those who of interventions—including BGM device education, give a low importance rating are essentially telling smartphone coaching keyed to blood glucose results, the provider that they lack the information, ability, or and counseling approaches linked to readiness to motivation to practice BGM.

The Role of Blood Glucose Monitoring in Diabetes Management 13 • “Why do you say 10 (or 9 or 8 or 7) and not lower?” incremental, achievable BGM goals. Change is rarely This paradoxical question and its answer provide an an all-or-nothing event, and identifying and achieving opportunity for the individual to rehearse reasons for an incremental goal (i.e., structured pre- and post-meal the importance of BGM. testing for 1 meal/day to assist with food choices or • For those who rate importance as a 6 or lower, the improved insulin dosing) can be the first step toward most important question to ask is, “What would achievement of broader goals negotiated in future it take—what would have to happen—for you to counseling exchanges. rate the importance of following the BGM pattern we’ve discussed as, say, a 7 or an 8 or a 9?” Here the Embracing the Spirit of Collaborative individual—the expert in what it would take to make Problem-Solving BGM personally important—may tell you exactly This approach to helping people with diabetes what it would take, and this can become the core of overcome obstacles to BGM is meant to suggest an the counseling intervention. The person—not the overall collaborative spirit of BGM counseling that provider—has offered a strategy to suit the situation. will enable diabetes care providers to triage PWD and This suggestion is followed by a discussion regarding identify those who can benefit from counseling, empa- how to make it happen. thize and legitimize their struggles, elicit strategies for • “On a scale of 1 to 10, where 1 is ‘not at all confident’ improvement, and negotiate achievable goals. and 10 is ‘completely confident,’ how confident are Attention to BGM performance and its use to inform you—how sure are you—that you can monitor your and facilitate meaningful self-management action blood glucose in the way that we’ve discussed?” is part of an ongoing support process. In subsequent A lower confidence rating generally means that a encounters, providers should check in concerning person lacks the behavioral skills to implement the the attainment of negotiated goals and potentially recommended pattern of testing or lacks motivation suggest a more challenging BGM goal moving forward. or resources to do so. For PWD who have achieved their goal, implement a • For those who rate their self-confidence high relapse prevention discussion; ask how they achieved (from 7 to 10), consider asking another paradoxical their success, and identify specific practices they can question: “Why did you say 10 (or 9 or 8 or 7) and not implement as needed in the future. For those who have lower?” This question gives people an opportunity to not met the negotiated goal, process their struggle to rehearse their strengths by explaining why they feel attain the goal and elicit an alternative strategy for confident about performing BGM. achieving it or modify the goal to make it more achiev- • For those rating their confidence as a 6 or lower, able. Repeat this process until BGM performance is the most important question to ask is, “What would stable, all the while continuing to empathize with the it take—what would have to happen—for you to struggles, elicit solutions to emerging challenges, and be, say, a 7 or an 8, or a 9 in confidence that you reinforce successes. could follow the BGM pattern we’ve talked about?” The approach to diabetes self-management and Here the individual—the expert in what it would BGM counseling described here is summarized in take to increase his or her self-confidence in BGM Figure 3. Clinicians interested in a more in-depth performance—can tell the clinician exactly what it discussion of this approach are encouraged to would take to do so. This can become the core of the consult references 57–60. Keep in mind that the counseling intervention. Again, the person—not the specific steps and wording provided here are only provider—has offered a strategy to suit the situation. illustrations. Many clinicians have had effective This suggestion is followed by a discussion regarding BGM support discussions by simply asking, “How’s how to make it happen. it going for you?” and “What would have to happen to Set Incremental, Achievable Goals make it work better?” Most importantly, remember Based on an exchange like the one described above, that PWD are your allies and experts in facilitiating diabetes care providers and PWD can negotiate their own behavior change.

14 The Role of Blood Glucose Monitoring in Diabetes Management STEP 1 USE OF BGM IN CGM USERS Set the agenda: “If it is okay with you, I’d like to talk Convenience and accuracy are characteristics of CGM about how you are doing with your diabetes.” that lead many to think CGM will, to a great extent, displace BGM. CGM systems are small and getting even STEP 2 smaller with each new generation, as well as becoming Assess self-management: “A lot of people struggle increasingly accurate. Although CGM is not as accurate with glucose checking and exercise. How is it going as the most accurate BGM systems, it surpasses the with you?” accuracy of many glucose meters available today (16,61). Importantly, the recent, rapid uptake of CGM is STEP 3 also the result, in part, of scientific data showing Reinforce success and prevent relapse OR choose improved clinical outcomes of reduced hypoglycemia a self-management practice to address: “Great and improved A1C levels using CGM compared to job with X. Do you want to talk about Y, or maybe about Z?” BGM or usual care (62–67). Furthermore, an impactful recent meta-analysis of randomized controlled trials STEP 4 demonstrated that CGM improves glucose outcomes by increasing glycemic time in range (TIR) and decreasing Rate importance: “On a scale of 1–10, how important is…?” time below range, time above range, and glucose variability in both type 1 and type 2 diabetes compared STEP 5 to usual care that included BGM (68). In its 2020 Standards of Medical Care in Diabetes— Rate confidence: “On a scale of 1–10, how confident are you?” 2020 (29), the American Diabetes Association (ADA) states that, “when used properly, real-time and inter- STEP 6 mittently scanned continuous glucose monitors in conjunction with insulin therapy are useful tools to lower Decide whether to focus on importance or confidence: If importance is low (<7), focus on it; if A1C levels and/or reduce hypoglycemia in adults with importance is high (>7) and confidence is low (<7), type 1 diabetes who are not meeting glycemic targets, focus on confidence; if both are high and self- have hypoglycemia unawareness, and/or have episodes of management is poor, focus directly on barriers and hypoglycemia . . . and in conjunction with insulin therapy how the person thinks he or she could overcome . . . to lower A1C levels and/or reduce hypoglycemia in them. Provide suggestions if necessary. adults with type 2 diabetes who are not meeting glycemic STEP 7 targets.” There is also considerable support for a broad range of intermittent use of CGM over time (using either Identify barriers to BGM and explore solutions: Elicit solutions from the person by asking the personal devices owned by PWD or professional CGM questions “Why did you say X and not lower?” systems owned by medical clinics) for evaluating CGM and “What would it take to make importance (or metrics and glucose patterns for PWD who use BGM but confidence) higher?” have not achieved their glucose targets. Despite the availability of high-quality CGM systems STEP 8 that can facilitate improvements in glucose manage- Negotiate and agree on an achievable and ment, uptake of this technology in clinical practice, realistic goal. while growing steadily, is still only about 50–75% in pediatric endocrine practices and 35–50% in adult STEP 9 endocrine practices for individuals with type 1 diabetes Subsequent clinical contact: Revisit the self- (69) and much lower for those with type 2 diabetes management goal, reinforce success, and strategize maintenance OR establish and strategize treated in primary care. The main barriers to uptake a new achievable goal. are cost, reluctance of patients to wear a CGM glucose sensor, and high time demands for implementation FIGURE 3 A Motivational Interviewing–inspired approach into usual clinical workflows coupled with inadequate to counseling PWD to address barriers to BGM. reimbursement for the extra time spent. Another likely barrier to use of CGM in the primary care setting is a

The Role of Blood Glucose Monitoring in Diabetes Management 15 A B

Subject ID: Example A Report Name AGP AGP Report: BGM Visit ID: Time Period: Last 90 days of data MRN

BGM STATISTICS BGM VALUES IN RANGES (For Checks Available) GLUCOSE STATISTICS AND TARGETS TIME IN RANGES % of Total Checks 18 Apr 2014–17 Jul 2014 91 days 21 Nov 2018–3 Dec 2018 13 days Very High (>250 mg/dL) ...... 1. 2%...... 28 Very High (>250 mg/dL) ...... 19% (4h 34min) % Time CGM is Active 99.9% Total Number of Checks...... 2. 39 Average Checks per Day...... 2.2 Glucose Ranges Targets [% of Readings (Time/Day)] Average Glucose...... 1. 73 mg/dL High (181–250 mg/dL) ...... 28%...... 67 Target Range 70–180 mg/dL ...... Greater than 70% (16h 48min) Average Before-Meal Glucose...... Unable to Calculate High (181–250 mg/dL) ...... 20% (4h 48min) Below 70 mg/dL ...... Less than 4% (58min) Average After-Meal Glucose...... Unable to Calculate Below 54 mg/dL ...... Less than 1% (14min) Lowest/Highest Glucose...... 4.3/388 mg/dL Above 180 mg/dL ...... Less than 25% (6h) Glucose Variability (percent coefficient of variation, %CV)...... 36.1% Above 250 mg/dL ...... Less than 5% (1h 12min) Target Range (70–180 mg/dL) ...... 49% (11h 46min) BGM TARGETS Target Range (70–180 mg/dL) ...... 58%...... 138

Average Glucose 165 mg/dL Fasting and Before-Meal Target...... 70-130 mg/dL Glucose Management Indicator (GMI) 7.3% Low (54–69 mg/dL) ...... 4% (58min) After-Meal Target...... Less than 180 mg/dL Low (54–69 mg/dL) ...... 2% ...... 5 Glucose Variability 49.4% Very Low (<54 mg/dL)...... 8% (1h 55min) Very Low (<54 mg/dL) ...... 0% ...... 1 AMBULATORY GLUCOSE PROFILE (AGP) AMBULATORY GLUCOSE PROFILE (AGP) AGP is a summary of glucose values from the report period based on blood glucose monitoring (BGM) data with median (50%), 25th and 75th percentiles shown as if occurring in a single day. AGP is a summary of glucose values from the report period, with median (50%) and other percentiles shown as if occurring in a single day.

350 350

95% 250 250

L 75% d / g

75% m mg/d/L

180 50% 180 50% e

50% g 25% n a R

25% t e g r a arget Range T T 5% 70 70

54 54

0 0 12 am 3 am 6 am 9 am 12 pm 3 pm 6 pm 9 pm 12 am 12 am 3 am 6 am 9 am 12 pm 3 pm 6 pm 9 pm 12 am

DAILY GLUCOSE PROFILES DAILY GLUCOSE PROFILES (Last 2 Weeks)

Wednesday Thursday Friday Saturday Sunday Monday Tuesday Each daily profile represents a midnight-to-midnight period. The more checks available throughout the entire day, the more opportunities for improvement. 21 22 23 24 25 26 27 Friday Saturday Sunday Monday Tuesday Wednesday Thursday 4 5 6 7 8 9 10

12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 12 pm 12 am 28 29 30 01 02 03 11 12 13 14 15 16 17

Patent pending – HealthPartners Institute dba International Diabetes Center – All Rights Reserved. 2020 Patent Pending – HealthPartners Institute dba International Diabetes Center – All Rights Reserved. 2019

FIGURE 4 AGP reports display glucose monitoring data for easy interpretation to facilitate shared clinical decision- making. Depicted are A) an AGP report derived from CGM data and B) an AGP report derived from BGM data. lack of clinician awareness regarding the availability require calibration. PWD also need to be able to verify of these systems and the potential benefits they may their glucose status when they are symptomatic and are provide. In addition, some PWD find the CGM alarms concerned that their CGM reading is not accurate. for fluctuating glucose and the increased volume of data collected via CGM to be stressful, and others may expe- Interpreting BGM and CGM Data for Clinical rience difficulties with skin irritation at sensor sites. Decision-Making Some have asked whether the availability of newer There are some principles in the use of BGM and CGM systems that do not require calibration and CGM that may enhance the effective use of each type are cleared for nonadjunctive insulin dosing (i.e., not of glucose monitoring. Forty years ago, PWD insisted, requiring confirmation of glucose levels via BGM) might often to their skeptical medical teams, that they wanted signal “the end of fingersticks” (70). However, despite the to perform their own glucose monitoring at home, even trend of increasing indications for CGM use and guid- if that meant using the crude lancet devices and slow ance to use BGM only when indicated (43) to minimize and only moderately accurate glucose meters of that era. unnecessary health care costs, in practice, most PWD More recently, some clinicians have worried that CGM are taught how to use a glucose meter as part of routine generates a potentially overwhelming level of data that self-management education, even if it is to be used only may be confusing to PWD. Once again, however, many intermittently (as is often the case in type 2 diabetes). PWD are making it clear that they find such information Still, the ability to perform BGM remains important even helpful and that they find the emerging terminology for PWD who use CGM because data are not available around the concept of TIR easy to understand (71). during CGM system warmup periods, and there will Efforts to standardize (72,73) and organize (74) be instances in which CGM systems malfunction or CGM data to facilitate interpretation have led to the

16 The Role of Blood Glucose Monitoring in Diabetes Management establishment of 10 core CGM metrics for clinical care; Although 14 days is the default standard for the CGM CGM targets for times below, in, and above glycemic AGP that includes several thousand glucose values, the ranges; and a recommended single-page CGM report AGP for BGM compiles 90 days of data with an average known as the ambulatory glucose profile (AGP) as a 2.2 checks/day and a few hundred total glucose checks starting point for CGM-informed clinical care. The summarized. The metrics are partly BGM-oriented, ADA has included these recommendations in its 2020 with the ability to calculate and display the average Standards of Care (29). pre- and post-meal glucose values if the individual manually marks these time points. The BGM targets AGP Report for CGM relate to the desired fasting, pre-meal, and post-meal A 2-week AGP report is usually generated from CGM glucose readings. In addition, there is the familiar color data at face-to-face or remote telehealth visits with bar of glucose ranges, but for the BGM report, this is not PWD who use CGM systems. As shown in Figure 4A, the called “Time in Ranges.” Rather, they are called “BGM AGP is a three-panel, one-page report showing the 10 Values in Ranges” because since these are intermittent core CGM metrics and CGM targets in the first panel. A BGM samples and do not cover the entire day. Instead, clinician or patient can review the Time in Ranges color the percentage of values that were in the standard bar to see if the recommended TIR target of glucose in glucose ranges are displayed, along with the number the range of 70–180 mg/dL for >70% of readings is being of glucose checks that actually comprise each range. met while also keeping the time-below-range metrics of The glucose profile in the middle panel shows all of the <70 mg/dL and <54 mg/dL to the recommended <4% and glucose values at the times they were taken, color-coded <1% of readings, respectively. This graphic display shows to indicate in-range, below-range, or above-range values. whether there is room for improvement. The second In addition, the median line and interquartile range are panel of the AGP shows a 2-week glucose profile previ- included only when there are enough data to generate ously known as a “modal day” or “standard day” data these summary metrics. This approach will often lead depiction. This panel identifies at a glance where in the to gaps in the AGP graphic, but this is a teaching point 24-hour period there is room for improvement. Recom- to indicate that, with BGM, there are times (usually mendations are to mitigate any periods of hypoglycemia overnight) during which there is uncertainty regarding first and then tackle any hyperglycemia or excessive glycemic status. Finally, like the CGM report, the AGP glycemic variability. The third panel depicts each of the BGM report ends with 2 weeks of individual day graphs daily glucose profiles from the 10–14 days of CGM use so the clinician can see whether there are patterns that make up panel 2. Reviewing these daily views helps of days with fewer tests performed that cannot be to sort out whether there are differences in glycemic discerned from the combined data in panel 2. outcomes between weekends and weekdays or if any particular day of the week stands out as needing atten- Intermittent Use of BGM and CGM tion. Clinicians and PWD alike have generally embraced Having a standardized and systematic approach to this one-page report that allows for a dialog about the displaying BGM and CGM data makes for a smoother collected data and facilitates shared decision-making on transition in glucose analysis when moving from BGM next steps toward improving glycemic management. to CGM use or when using BGM and CGM intermit- tently. Are there data supporting the intermittent use AGP Report for BGM of both methods of glucose monitoring in the manage- Although BGM had a 20-year head start on CGM, there ment of type 1 or type 2 diabetes? This topic was nicely has not been a similar concerted effort until now to reviewed from the perspectives of PWD, HCPs, and generate a consensus BGM report similar to the one that health systems by Ziegler et al. (76), who concluded has been so helpful in encouraging the uptake of CGM, that the question of intermittent monitoring requires despite the fact that the original AGP report conceived much more discussion. by Mazze et al. (75) in 1987 was developed for BGM For most individuals with type 1 diabetes, use of data. Figure 4B shows a sample AGP report generated CGM is recommended on a continuous basis as much by an expert panel at the International Diabetes Center, as is financially and socially acceptable (77). Many using BGM rather than CGM data. Where possible, individuals with type 2 diabetes who are not on a it follows the CGM version of the AGP (Figure 4A), multiple daily injection (MDI) insulin therapy regimen including three graphic panels in a one-page report. but who have not achieved their glycemic targets

The Role of Blood Glucose Monitoring in Diabetes Management 17 might also consider intermittent use of CGM and refer to these scenarios as logical cases and anecdotal BGM. Professional CGM systems may facilitate this experiences because we currently lack randomized trials strategy for such patients. In this type of intervention, or even cohort-matched studies in real-world settings clinic-owned CGM systems are provided to PWD for to confirm for larger numbers of PWD that intermittent 10- to 14-day wear periods, either blinded or providing CGM and BGM is an effective strategy (78). real-time glycemic data. The data are then also evalu- More data are also needed on the appropriate use of ated retrospectively during a clinic or telehealth visit BGM, CGM, and intermittent use of either or both in the to assess the current state of management and look for real-world primary care setting. In 2018, an Italian team glucose patterns. In addition, PWD can use a real-time studied BGM in >13,000 individuals with type 2 diabetes CGM system intermittently, such as for 10–14 days from 21 clinical centers and concluded that, regardless once every 2–3 months, to get the value of real-time of PWD’s therapeutic regimen, BGM was poorly utilized reinforcement of good food and exercise choices. (defined as mostly fasting BGM, no structured BGM checking that might reveal glucose patterns, and overall Logical Cases and Positive Anecdotal Experience very little BGM checking that would be helpful in The most logical cases in which to use BGM and CGM guiding glycemic management) (79). One recent review intermittently are those in which PWD seem to value of both BGM and CGM concluded that we will probably the data from CGM but do not want or cannot afford continue to see a mix of BGM and CGM use and, in many to wear a sensor continuously. In such cases, PWD cases, a combined use of both monitoring methods (80). can get the CGM-derived AGP and daily views during Both CGM and structured BGM can generate data to intermittent CGM use to help identify the times of day assist with pattern recognition and inform lifestyle when there is room for the most improvement (i.e., very changes and medication adjustments. low or very high glucose levels) and then target those time periods with intermittent BGM. For example, if the person whose data is represented in Figure 4A could INNOVATIONS IN BGM only afford or only wanted intermittent CGM use, that The use of BGM has been found to assist many PWD in person could focus BGM between 3:00 and 7:00 a.m. and achieving their glycemic targets (50,81,82). Traditional again between 7:00 and 8:00 p.m. to minimize potentially glucose meters display and store glucose measurements dangerous hypoglycemia and hyperglycemia, respec- within the device. These data need to be retrieved tively, until another intermittent CGM AGP could be before they can be analyzed by users or clinicians to generated. Having the PWD direct BGM according to the guide treatment. Innovative technologies such as digital previous CGM AGP can provide motivation for making health apps that display and summarize individual lifestyle changes. It can also help to overcome clinical blood glucose measurements and incorporate additional inertia, leading to shared decision-making regarding any relevant data such as insulin doses, meals/snacks, and necessary therapeutic changes. physical activity, can further support self-management One clinical scenario in which intermittent use of while decreasing disease burden and benefitting overall CGM seems particularly beneficial anecdotally is to diabetes care (83). Integration of BGM with insulin provide a detailed glucose profile when considering calculators, automated insulin titration software, and adding a glucagon-like peptide 1 receptor agonist or basal remote coaching are further developments that will be insulin to a regimen of metformin and a sulfonylurea reviewed in this section. (usually reducing or stopping the sulfonylurea in the process). A second scenario in which intermittent CGM Diabetes Apps and Data Management may be beneficial is to facilitate intensification from a basal insulin regimen. Often in such cases, there is a Regulations and Recommendations classic stair-step pattern of rising glucose after each meal More than 1,500 mobile apps support diabetes manage- until a person is very hyperglycemic at night, requiring ment, many of which incorporate BGM. Digital health large doses of basal insulin to try to normalize glucose apps used for diabetes management include options levels by morning. In such instances the picture afforded that focus on nutrition, physical activity, glucose by the CGM-derived AGP is so clear that PWD may agree monitoring, insulin titration, and insulin delivery. to add mealtime insulin and adjust their basal insulin These apps are generally intended to improve health doses downward to smooth out the glucose profile. We outcomes by coaching PWD, supporting healthy eating

18 The Role of Blood Glucose Monitoring in Diabetes Management and weight management, encouraging BGM, and (22,85,86). Mobile apps that provide insulin dose helping with interpretation of glucose data and identifi- calculations are considered medical devices; those that cation of glycemic patterns (22). track, record, or make behavioral suggestions about Although the field of digital health apps has been fitness, health, or wellness (e.g., dietary logs, calorie developing rapidly, regulations and guidelines have counters, and activity monitors) are not considered lagged behind. Mobile apps are still largely unregulated medical devices (85). FDA-cleared glucose meter– unless they meet the definition of a medical device for connected apps are described in Table 10. therapeutic or diagnostic purposes. Recently, however, Although digital health apps have great potential to regulatory agencies in the United States and abroad benefit PWD, they can generate challenges for clini- have recognized the rapid growth of this market and cians. HCPs need to understand not only the potential have released guidelines and policies (22). Many benefits, but also the potential risks with regard to data European countries assess whether a product meets confidentiality, security, accuracy, and reliability (22). the standards set by the E.U. Medical Device Directive Readers are referred to a recently published consensus (84). In the United States, the FDA in 2019 released report from the Diabetes Technology Working Group of an updated version of its Policy for Device Software the ADA and the European Association for the Study of Functions and Mobile Medical Applications (85). Diabetes for a detailed review of this topic and recom- The FDA requires evidence of safety, performance, mendations for the use of this technology in clinical and clinical effectiveness, using a risk-based approach practice (22).

TABLE 10 FDA-Cleared Glucose Meter–Connected Apps Automatic Apple/Android Brand Description and Compatible Meter(s) Synchronization? Compatibility? Contour Contour Next One meter Yes Yes Diabetes • Testing reminders (Ascensia • Customizable graph view Diabetes • Color-coded glucose levels Care) • Alerts for critically high or low blood glucose levels • Compatible with Apple Health • Ability to share reports with HCP Dario Dario Blood Glucose Monitoring System Yes Yes, including (Dario Health) • Digital logbook with trends Apple Watch • Automatic unlimited test strips refills • Carbohydrate counter • Hypoglycemic alerts shared to up to four people via text message and GPS • Three levels of subscription (basic, pro, and premium) Glooko Compatible with >70 meters and numerous insulin pumps and CGM Yes, for Yes (Glooko) devices Bluetooth-enabled • Testing reminders meters • Medication reminders • Customizable reminders • Customizable graph view • Compatible with Apple Health, iHealth, and Fitbit • Can synchronize with HCP practice accounts • Ability to share reports with HCP iHealth Gluco- iHealth Gluco and Align glucose meters Yes Yes, including Smart • Offers free Cloud data storage Apple Watch (iHealth Labs) • Medication reminders • Ability to share reports with HCP Lifescan OneTouch Verio Flex meter Yes Yes OneTouch • Color-coded logbook and dashboard Reveal • Customizable graph view (Lifescan) • Automatic notifications for repeated hypoglycemia or hyperglycemia values • Ability to share reports with HCP continued on next page

The Role of Blood Glucose Monitoring in Diabetes Management 19 TABLE 10 continued from previous page Automatic Apple/Android Brand Description and Compatible Meter(s) Synchronization? Compatibility? Livongo Livongo cellular-enabled meter Yes Yes (Livongo • Testing reminders Health) • Custom alerts to automatically notify friends/family after an out- of-range reading • Live coach available 24/7 via text or call for out-of-range readings • Ability to share reports with HCP • Expert coaching (by a CDCES) to advise on lifestyle, diabetes, and blood pressure • Available primarily through employers or health care systems mySugr Bluetooth-enabled Accu-Chek meters Yes Yes (mySugr/ • Ability to share glucose data with others via text message Roche • Customizable reports Diabetes • Accu-Chek bolus advisor Care) • Can synchronize with HCP practice accounts • Clinicians’ online portal home page One Drop One Drop meter Yes Yes, including (One Drop) • Medication reminders Apple Watch • One Drop Personal Diabetes Assistant, allowing logging of other relevant data • Automated decision support • Built-in food database with macronutrient and calorie counter • Scans barcodes on packaged foods • One Drop Predictive Insights machine learning algorithm • Tracks activity with a smartphone’s pedometer • Compatible with Apple Health, Google Fit, and FitBit • Ability to share reports with HCP • Personal diabetes coach option with CDCES: SugarRx (additional cost/month) Patterns for POGO Bluetooth-enabled meter Yes Yes POGO • Reminders and alerts via push notifications, text, or email for (Intuity low and high glucose Medical) • Testing schedule reminders • Medication schedule reminders • Sharing Circle: invite friends/family to view data and receive glucose alerts • Personal coaching with a CDCES (added cost per month) • Compatible with Fitbit, Strava, Apple Health, and MyFitnessPal • Ability to share reports with HCP CDCES, certified diabetes care and education specialist; GPS, global positioning system.

Cloud-Based Solutions in BGM pattern recognition and facilitate shared Busy practitioners are often presented with multiple decision-making. BGM communications from PWD, who use many The Glooko platform (https://glooko.com, Glooko) different meters and may send in handwritten data is available to practices by subscription (87). It allows logs or use meter-specific proprietary downloading rapid in-clinic or remote uploading of data from >70 software and nonstandardized data reports. In addi- different glucose meters and numerous insulin pumps tion, the lack of integration of these reports with HCPs’ and CGM systems (Figure 5) and potential integration electronic medical record (EMR) systems makes the into EMR systems. The Tidepool platform (https://tide- documentation of glucose levels cumbersome. These pool.org, Tidepool Project), run by a nonprofit organiza- problems have led to the development of Cloud-based, tion, provides free software for PWD and clinicians to device-agnostic diabetes data management systems, upload, share, and review data from >25 meters, as well the largest of which are Glooko (known in Europe as most insulin pumps and CGM devices (Figure 6). as Diasend-Glooko) and Tidepool. Both provide Tidepool has a “copy as text” feature, enabling copying users with standardized reports that can assist and pasting of BGM data into clinic notes (88).

20 The Role of Blood Glucose Monitoring in Diabetes Management A

B

FIGURE 5 Glooko BGM log. A) Overview of blood glucose values with color-coded dots, from low to high (red = <70, green = 70–180, and orange = >180 mg/dL). Bottom panel shows glucose mean and SD. B) Overlay of 14 days of blood glucose values graphed by time of day showing median, lowest and highest averages, and percentiles (25–75% and 10–90%). Bottom panel shows glucose mean and SD, number of glucose readings/day, and percentages of glucose levels in the target range (green; 70–180 mg/dL), above range (orange; >180 mg/dL and >250 mg/dL), and below range (red; <70 mg/dL and <54 mg/dL).

The Role of Blood Glucose Monitoring in Diabetes Management 21 A

B

FIGURE 6 Tidepool BGM log. A) Blood glucose values with color-coded dots, from low to high (red = <54, orange = <70, green = 70–180, lilac = >180, and purple = >250 mg/dL). B) Overlay of 14 days of blood glucose values graphed by time of day with average bars depicting 3-hour blocks, in green if blood glucose is 70–180 mg/dL. On the right panel is a “copy as text” feature, average glucose value with SD, and average daily readings in range (green; 70–180 mg/dL), above range (lilac; >180 mg/dL and purple; >250 mg/dL), and below range (orange; <70 mg/dL and red; <54 mg/dL).

22 The Role of Blood Glucose Monitoring in Diabetes Management Although diabetes apps have tremendous potential insulin pumps, but many PWD who use an MDI insulin (89), barriers exist for many individuals. These regimen instead of a pump can also benefit from such a include low literacy and numeracy levels, inability or tool to improve their dosing accuracy. Dose calculators challenges with regard to using smartphone or other are preprogrammed with a user’s ISF, individualized smart devices (e.g., older adult or those with impaired I:C ratio, and target glucose range. When users enter a vision or hearing); costs, low digital (i.e., computer or blood glucose reading and the amount of carbohydrate Internet) literacy, limited Internet access, and insuf- they intend to eat, the calculator will provide a recom- ficient broadband Internet service or “dead zones” in mended insulin dose. urban and rural settings (22,83,90). Numerous insulin calculator apps are available, but the accuracy and reliability of some are poor. An Insulin Dose Calculators evaluation of 46 such apps found that two-thirds Successful diabetes self-management enables PWD to posed a risk for inappropriate dosing (92,93). There- achieve their glycemic goals and is especially important fore, clinicians must proceed with great caution for those on insulin therapy (45). Intensive insulin when recommending an insulin dose calculator to therapy requires the completion of multiple complex limit exposure of PWD to incorrect calculations that daily tasks. These include monitoring glucose levels could result in erroneous insulin dosing recommen- before meals and at bedtime; counting carbohydrates dations with potentially catastrophic results. and calculating insulin doses for each meal or using fixed insulin doses with carbohydrate-consistent meals; Eiland et al. (94) identified 20 diabetes self- adjusting insulin doses to correct hypoglycemia or management apps that were cleared by the FDA or hyperglycemia; and calculating correction doses based bore a CE (European Conformity) mark and had on an individualized ISF or a predetermined insulin evidence of efficacy, safety, or feasibility reported algorithm. All these actions must be performed every in peer-reviewed literature. Of these 20 apps, day to achieve and maintain euglycemia and avoid fewer than half contained insulin dose calculators. short- and long-term complications. These tasks can Since 2019, insulin dose calculator apps have been be especially challenging for PWD with low literacy or considered medical devices and are regulated by numeracy levels (91). the FDA (86,94). Those available in the United Insulin dose calculators are incorporated into States are described in Table 11.

TABLE 11 Insulin Dose Calculators Available in the United States Regulatory Clearance/ Brand Platform Marking Description Accu-Chek Connect Meter, FDA • Prescription only (Roche Diabetes Care) phone app • Insulin calculator provides bolus recommendations taking into account multiple variables Glooko Mobile Insulin Phone app FDA • Prescription only Dosing System • Long-acting insulin dose recommendations according (Glooko) to the parameters set by the clinician InPen Phone app FDA • Prescription only (Companion Medical) • Bolus calculator tracks insulin doses Insulia Phone app FDA/CE • Prescription only (Voluntis) • Long-acting insulin dose calculator with treatment algorithm entered by the clinician iSageRx Phone app FDA • Prescription only (Amalgam Rx) • Long-acting insulin dose calculator with treatment algorithm entered by the clinician or from a validated algorithm from research studies My Dose Coach Phone app FDA • Long-acting insulin dose calculator based on the (Sanofi) algorithm recommended in American Association of Clinical Endocrinologists guidelines

The Role of Blood Glucose Monitoring in Diabetes Management 23 Connected Care Artificial Intelligence The term “connected diabetes care” (95) refers to Artificial intelligence (AI) decision-support systems diabetes management systems that use smartphone are becoming commercially available and have apps, connected devices, and remote human and the potential to improve diabetes management by automated coaching. The goal of such systems is to providing tools to automate insulin titration and dose provide PWD with remote education, coaching, and adjustment recommendations for PWD on insulin communication to augment their usual care and therapy. One such system is the DreaMed Advisor Pro improve self-management and outcomes. (https://dreamed-diabetes.com, DreaMed), which Most such systems use connected BGM. Some received FDA clearance in 2018. programs use a business-to-business-to-consumer With this system, data from CGM or BGM and insulin model, providing the program to an employer or pumps are uploaded to a data management system such insurer, which in turn offers it to PWD, and some as Tidepool or Glooko. After uploading and analyzing offer peer support and an interactive curriculum. the data, the Advisor searches for hyperglycemic or All connected diabetes care companies with remote hypoglycemic patterns and produces an insulin titra- human coaches employ teams of diabetes care and tion recommendation for optimization of insulin pump education specialists, nurses, dietitians, and exercise settings. Future versions are expected to incorporate scientists. Presently, Virta Health (https://virtahealth. smart insulin pens for patients using an MDI insulin com) and Onduo Health (https://onduo.com) consider regimen. Clinicians can review the automated recom- themselves to be virtual medical clinics and employ mendations, edit them, and share them with PWD physicians who can prescribe and titrate medica- either during a visit or electronically. In the future, tions (96,97). The most salient features of selected availability of additional AI systems is anticipated. connected care companies and their key published To summarize, diabetes self-management is often data are summarized in Table 12 (98–113). limited by the absence of real-time BGM data needed

TABLE 12 Major Connected Diabetes Care Companies and Published Evidence of Their Impact Peer Prescribing Published Research, Study Company Support? HCPs on Team? Type, Year, n, Reference Key Findings Canary Health Yes No • Non-RCT, 2018, 558 (98) • Cost savings

Cecelia Health No No • Non-RCT, 2017, 181 (99) • 2.4% A1C reduction at 6 months • Non-RCT 2020, 34, (100) • 1.1% A1C reduction at 3 months

Livongo Health Yes No • Non-RCT, 2017, 4,544 (101) • Fewer hypoglycemia and • Non-RCT, 2018 330 (102) hyperglycemia events • Non RCT, 2019, 86 (103) • 1% A1C reduction at 34 weeks • 0.66% A1C reduction at 1 year mySugr Bundle Yes No • Non-RCT, 2019, 52 (104) • Increase in glucose testing (mySugr/Roche) frequency

Onduo No Yes • Non-RCT, 2018, 44 (105) • 1.3% A1C reduction at 6 months • Non-RCT, 2020, 612 (106)

One Drop Yes No • Non-RCT, 2017, 1,288 (107) • 1.27% A1C reduction at 4 months • Non-RCT, 2017, 256 (108) • 1.36% interval A1C reduction • Non-RCT, 2018, 127 (109) • 0.86% A1C reduction at 12 weeks Virta Health Yes Yes • Non RCT, 2017, 329 (110) • 0.9% A1C reduction at 2 years

BlueStar No No • RCT, 2008, 30 (111) • 2.03% A1C reduction (Welldoc/Lifescan) • RCT, 2011, 163 (112) • 1.9% A1C reduction • RCT, 2019, 223 (113) • No A1C difference RCT, randomized controlled trial.

24 The Role of Blood Glucose Monitoring in Diabetes Management to make informed decisions to help PWD achieve and The recommended frequency of BGM should be indi- maintain their glycemic targets. The advent of mobile vidualized. People with type 1 diabetes will generally need health apps allows PWD to use their glucose meters in to perform BGM 4–10 times/day, whereas those with type a partner-based model, through which app-based BGM 2 diabetes who are at or near their glycemic targets and becomes a “health companion,” providing reminders not taking medications that can cause hypoglycemia for performing BGM and taking medications and may use BGM less frequently or not at all (Table 3). offering immediate feedback and graphic depictions Pattern recognition, including identifying glycemic of current glycemic status. Device-agnostic software excursions related to eating, physical activity, stress, platforms can enable clinicians’ easy review and and illness, is important and should be used to help assessment of BGM data as displayed in standardized direct treatment. The use of structured BGM profiles reports, facilitating treatment optimization. For PWD such checking before and after meals, before and after using MDI insulin therapy, insulin dose calculators, as exercise, and at bedtime and fasting, can assist in stand-alone tools or integrated into insulin pens, can adjusting food, physical activity, treatment regimens, ease the burden of complex dose calculations. and medication dosing. BGM also is needed when However, challenges remain. Regulatory agencies hypoglycemia is suspected and, for PWD using insulin, must ensure that available apps are safe (i.e., accurate), before driving or performing other crucial tasks (29). and HCPs need improved access to FDA-cleared apps Adopting a counseling strategy that focuses on the and the knowledge and confidence to use them in clin- information, motivation, and behavioral skills PWD ical practice. Apps should be affordable and available need to succeed and incorporates the use of negotiated, in multiple languages, and access to smartphones and incremental, achievable goals that are elicited, if Internet services must be expanded. possible, from PWD rather than HCPs, will facilitate efficient and effective use of BGM. CONCLUSION Differences abound in the ability of various Throughout the past several decades, BGM has been glucose meters to communicate with other glycemic fundamental for optimal diabetes self-management, management systems. Integration of meters with and it will remain an important tool for PWD for Cloud-based data management systems facilitates years to come. BGM devices have become smaller remote monitoring. The use of additional innovations and more accurate and now require less blood and such as insulin dosing calculators, smartphone apps, include more features such as Cloud-based data remote coaching, and artificial intelligence systems is management systems and connectivity to other on the rise, and their availability and accessibility are devices. The accuracy of BGM is crucial because its expected to expand. results are used to direct therapy. Glucose monitoring can now be accomplished via Accuracy can vary among devices. Errors can CGM as well as BGM. The ADA recommends that be caused by use of expired, improperly stored, or PWD who use CGM have the ability to perform BGM damaged strips; poor technique, including inade- to verify readings when symptomatic, if they are quate site cleansing; conditions such as hypoxemia concerned that their CGM transmitter or sensor is not and anemia; and the use of high-dose vitamin C working properly, and to calibrate certain CGM devices and acetaminophen. Over the years, the standards per manufacturers’ instructions (29). In general, the required to gain FDA clearance have become more use of CGM is costlier than BGM and is not necessary stringent (9), and more accurate glucose meters are for people with type 2 diabetes who are not treated now available in the marketplace. However, there is with insulin and are maintaining their glycemic goals. no formal re-evaluation of meters after clearance to For those who have not achieved their glycemic goals, ensure continued device accuracy. directed BGM based on glucose patterns observed BGM is only helpful if PWD know how to view, through the intermittent use of CGM can help PWD interpret, and act on their results. Education is make needed lifestyle and medication adjustments. essential in this regard. PWD need to learn proper As countries worldwide struggle with health care technique, overcome barriers to use, and receive costs, it is important for all HCPs to recommend training in understanding and using their results to glucose monitoring approaches that are cost-effective. optimize glycemic management. BGM is less expensive than CGM and sufficient for

The Role of Blood Glucose Monitoring in Diabetes Management 25 many people with type 2 diabetes. BGM also needs W.A.F. has received research support and has been a to be available for people using CGM. The ability to consultant to and speaker for Ascensia and Roche. download, examine, interpret, and transmit stored D.A.G. is a consultant for Lifescan and Lifescan glucose data facilitates communication with HCPs and Diabetes Institute; serves on an advisory board for empowers PWD to make health decisions to manage Novo Nordisk; in addition to her consulting work and their condition. When used as part of a diabetes prior to the publication of this compendium, she was hired as an employee of Dexcom. management plan and with appropriate support, BGM can help PWD better reach their glycemic goals. L.A.Y. has received research support from the American Diabetes Association, Bayer, Boehringer Ingelheim, Dexcom, Johnson & Johnson, Lexicon, Acknowledgments Novo Nordisk, Sanofi, and vTv Therapeutics. Editorial and project management services were No other potential conflicts of interest relevant to this provided by Debbie Kendall of Kendall Editorial work were reported. in Richmond, VA. The authors acknowledge the important contributions of Pat Stenger, RN, CDCES, Author Contributions and Holly Schachner, MD, to the section titled Lead author R.S.W. reviewed all content and wrote “Overcoming Barriers to BGM” and of Gregg D. the introduction and conclusion. G.A. wrote the Simonson, PhD, to the subsections on the AGP section titled “Innovations in BGM.” T.S.B. wrote reports for CGM and BGM in the section titled “Use the section titled “BGM Accuracy.” R.M.B. wrote of BGM in CGM Users.” section titled “Use of BGM in CGM Users.” W.A.F. wrote the section titled “Overcoming Barriers to Dualities of Interest BGM.” D.A.G. wrote the section titled “Using BGM R.S.W. has received research support through her Data to Achieve Treatment Goals.” L.A.Y. wrote the institution from Boehringer Ingelheim, Diasome, section titled “Recommendations for BGM Use.” All Eli Lilly, Insulet, Kowa, Medtronic, and Tolerion and authors reviewed and edited the manuscript and receives royalty payments from Wolters Kluwer approved the final version for publication. R.S.W. is Health (Up-to-Date). She has also received honoraria the guarantor of this work. for presentations from the American Diabetes Association. References G.A. has served as a consultant for Dexcom and 1. Howe-Davies S, Holman RR, Phillips M, Turner RC. Insulet, and her institution has received research Home blood sampling for plasma glucose assay in grant support from AstraZeneca, Dexcom, Eli Lilly, control of diabetes. BMJ 1978;2:596–598 Insulet, and Novo Nordisk. 2. Skyler JS, Lasky IA, Skyler DL, Robertson EG, Mintz T.S.B. has received research support from Abbott, DH. Home blood glucose monitoring as an aid in Capillary Biomedical, Dexcom, Diasome, El Lilly, diabetes management. Diabetes Care 1978;1:150–157 Kowa, Lexicon, Medtronic, Medtrum, Novo Nordisk, 3. Hirsch IB. History of glucose monitoring. In Hirsch REMD, Sanofi, Senseonics, Viacyte, vTv Therapetics, IB, Battelino T, Peters AL, Chamberlain JJ, Aleppo and Zealand Pharmaceuticals; honoraria for G, Bergenstal RM. Role of Continuous Glucose consulting from Abbott, Lifescan, Novo Nordisk, and Monitoring in Diabetes Treatment. Arlington, Va., Sanofi; and honoraria for speaking engagements American Diabetes Association, 2018 from Medtronic and Sanofi. 4. Diabetes Control and Complications Trial R.M.B. has received research support from, consulted Research Group; Nathan DM, Genuth S, Lachin J, for, or been on a scientific advisory board of Abbott et al. The effect of intensive treatment of diabetes Diabetes Care, Ascensia, DexCom, Hygieia, Johnson & on the development and progression of long-term Johnson, Lilly, Medtronic, Novo Nordisk, Onduo, Roche, complications in insulin-dependent diabetes mellitus. Sanofi, and United Healthcare. His technology research N Engl J Med 1993;329:977–986 is funded in part by the National Institutes of Health/ National Institute of Diabetes and Digestive and Kidney 5. American Diabetes Association. Consensus Diseases and the Leona M. and Harry B. Helmsley statement on self-monitoring of blood glucose. Charitable Trust. R.M.B.’s employer, the nonprofit Diabetes Care 1987;10:95–99 HealthPartners Institute, contracts for his services, and 6. Joint Committee for Guides in Metrology. no personal income goes to him for these services. International Vocabulary of Metrology – Basic and

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