<scp>ISPAD</scp> Clinical Practice Consensus Guidelines 2022: Diabetes technologies: Glucose monitoring

Abstract

Since publication of the 2018 guidelines, the area of glucose monitoring has evolved, especially as regards continuous glucose monitoring (CGM) systems. CGM is more widely available in many parts of the world; latest generation devices are factory-calibrated, more accurate, and do not need a confirmatory fingerstick blood glucose measurement. More studies regarding the efficacy of CGM systems, irrespective of the type of insulin delivery, are available including long-term observational studies. With increased availability and wider use, practical considerations related to daily CGM use (e.g., skin issues, physical activity) as well as educational and psychosocial aspects have come to the fore, which are also addressed in this chapter. Regular self-monitoring of glucose (using accurate fingerstick blood glucose [BG] measurements, real-time continuous glucose monitoring [rtCGM] or intermittently scanned CGM [isCGM]), is essential for diabetes management for all children and adolescents with diabetes. A Self-monitoring of glucose has a pivotal role in the management of insulin-treated children and adolescents with diabetes. It tracks immediate and daily glucose levels including periods of hypo- and hyperglycemia, helps guide insulin dose adjustments, facilitates evaluation of therapy responses and achievement of glycemic targets in a safe and effective manner. Along with major clinical trials demonstrating the superiority of intensive insulin therapy in persons with T1D in the early 1990s,1 self-monitoring of capillary blood glucose (SMBG) using hand-held portable meters in combination with glucose test strips and a lancet became the most widely used method of glucose monitoring, replacing urine glucose testing. In recent years, systems for continuously monitoring interstitial fluid glucose concentrations, CGM, using subcutaneously placed glucose sensors have become standard of care in T1D in many countries, particularly for children, adolescents, and young adults,2 and have been successfully employed for insulin-treated type 2 diabetes.3 The purpose of this chapter is to review and update the evidence on glucose monitoring devices (i.e., SMBG and CGM) in children, adolescents, and young adults and to provide practical advice and approaches to their use. Early SMBG measurement methods relied upon reflectance assays coupled with oxidation of glucose allowing for a colorimetric readout. Currently available glucose meters use an electrochemical method with an enzyme electrode containing either glucose oxidase or glucose dehydrogenase. There is considerable variation in the accuracy of widely-used BG monitors.4 Most reliable data are provided by meters meeting current international accuracy standards. The two most used standards are those of the International Organization for Standardization (ISO) (ISO 15197:2013) and the U.S. Food and Drug Administration (FDA) (Table 1). ISPAD recommends exclusive use of glucose meters that achieve these standards. Health care professionals should choose and advise on meters that are accurate and familiar to them as well as affordable to the person with diabetes. 95% within 15% for BG ≥100 mg/dl 95% within 15 mg/dl for BG <100 mg/dl 99% in A or B region of consensus error grida 95% within 15% for all BG in the usable BG rangeb 99% within 20% for all BG in the usable BG rangeb 95% within 12% for BG ≥75 mg/dl 95% within 12 mg/dl for BG <75 mg/dl 98% within 15% for BG ≥75 mg/dl 98% within 15 mg/dl for BG <75 mg/dl The specified accuracy standard achieved during controlled conditions might vary significantly from actual SMBG meter performance in real-world settings.4 Detailed information on the actual performance of SMBG devices is provided by The Diabetes Technology Society Blood Glucose Monitoring System Surveillance Program (www.diabetestechnology.org/surveillance/). SMBG accuracy depends on proper hand washing with complete drying9 and requires proper blood application and use of adequately stored, unexpired test strips, which are not counterfeit nor preowned/second hand.10 Providers and persons with diabetes/caregivers need to be aware of additional factors that can impair meter accuracy: Due to the enzymatic electrochemical reaction, monitors are sensitive to temperature and have a defined operating temperature range.10 Typically, an error message is displayed if the temperature is out of range. Unlike glucose dehydrogenase-based meters, glucose oxidase meters are sensitive to the ambient oxygen and should only be used with capillary blood of people with normal oxygen saturation. Low oxygen tensions (i.e., high altitude, hypoxia, venous blood readings) may result in falsely high glucose readings, higher oxygen tensions (i.e., arterial blood) may lead to falsely low readings.10 There are also several substances that may interfere with glucose readings (Table 2).10 Expert BG meters have integrated bolus advisors to calculate insulin dosages. Randomized controlled trials (RCTs) have shown use of a bolus calculator significantly increases the number of people achieving HbA1c targets and reduces hypoglycemia.11-13 Successful intensive insulin management requires at least 6 to 10 checks per day, appropriate response to the observed values, and regular, frequent review of the results to identify patterns requiring adjustment to the diabetes treatment plan.15 This includes review by the person with diabetes and their caregivers/family in addition to consultation with the diabetes care team. In resource-limited settings, availability and affordability of glucose meters and test strips are not guaranteed. Even though many children are on multiple daily injection regimens, only a few can afford frequent BG testing needed to optimize diabetes management. Very often testing is performed 3–4 times a day (i.e., pre-breakfast, pre-lunch, pre-dinner, and at bedtime). However, many persons with diabetes must resort to two times daily, that is, before breakfast and before dinner. If there are no BG monitoring capabilities, then urine testing is performed. For a comprehensive discussion on aspects of diabetes management in resource-limited settings, including glucose monitoring, please refer to the ISPAD 2022 Consensus guidelines Chapter 25 on ‘Management of Diabetes in Children and Adolescents in Limited Resource Settings. Rapid, capillary assessments of BG concentrations have been instrumental in permitting achievement of recommended targets over the past 30 years. However, SMBG only provides single snapshots of glucose concentrations. Consequently, episodes of hyper- and hypoglycemia, in particular nocturnal and asymptomatic episodes, as well as considerable fluctuations in BG concentrations may be missed and therefore not factored into treatment decisions. The emergence of CGM in the late 1990s represented a significant therapeutic milestone. Instead of single-point measurements of capillary blood glucose concentrations, CGM devices measure interstitial glucose concentrations subcutaneously at 1–15 min intervals using enzyme-coated electrodes or fluorescence technology. Significant improvements in device technology over the past decade (including improved accuracy, approval for non-adjunctive use, and reduced need for calibration), availability, smaller size, remote monitoring capability, and overall personal acceptance of CGM systems have contributed to the widespread adoption of this technology in clinical practice. In many countries, CGM use has now become the standard of care for people with T1D.2 According to data from German and Austrian DPV and U.S. T1D Exchange registries, CGM use increased exponentially from 2011 to 2017 in all pediatric age-groups (DPV: 4% in 2015 to 44% in 2017; T1DX: 4% in 2013 to 14% in 2015 and to 31% in 2017), with the highest use among preschool-aged and early school-aged children.17 From 2017 to 2020, further increase in CGM use among individuals with diabetes aged <25 years was seen in both registries each year for all age ranges (DPV: 40% in 2017 to 76% in 2020; T1DX: 25% in 2017 to 49% in 2020).18 Recent data from the Australasian Diabetes Database Network (ADDN) registry and the Australian National Diabetes Service Scheme (NDSS) demonstrate 79% of registry participants with T1D aged <21 years are using CGM.19 DPV and T1D Exchange registry data indicate significant disparities in CGM use by socioeconomic status (SES). Of note, in the T1D Exchange registry, the gap of device use between highest and lowest SES quintiles (52.3% vs. 15.0%) was more pronounced than in the DPV population (57.1% vs. 48.5%).20 Adequate clinic-specific resources and interventions to identify and overcome barriers to CGM uptake are necessary to promote CGM adoption and continued use.21 In a multiclinic quality improvement initiative of the T1D Exchange interventions of person and and of the clinical as well as with and to increases in CGM use from to in adolescents and young adults over CGM or the widely used CGM for the by in CGM systems glucose data which are not to the provide care professionals with data glucose and In addition to clinical CGM systems are employed in to glucose data and to (e.g., in people may from their their CGM readings in CGM CGM systems glucose at intervals and can glucose levels hypo- or as well as for glycemic available systems glucose data to data can then be and on a and used for remote monitoring by and In addition to sensors with a from 6 to a long-term for to use is available that approval in the in and in Of note, the CGM is only for use in adults over years of requires a performed by a or a Unlike CGM glucose is using the electrochemical the The CGM has long-term with daily scanned CGM In the Glucose Monitoring System Diabetes was a CGM intermittently scanned CGM devices do not glucose at glucose levels only the the by a or a to or over the interstitial glucose levels and glucose as well as a of current and glucose readings are provided on with glucose data from can be from a to a for remote glucose monitoring by or care The can provide glucose to a The generation of was in in 2018 and in the in sensors have higher accuracy and for adults and in addition to the capabilities, have to persons in the glucose is out of the range. the actual the must the The the is a real-time and real-time readings the need to It in The accuracy and of generation CGM systems to those of capillary BG the past 10 years, there has been continued improvement in the between actual BG and CGM to in the and glucose levels are a this is to the of min between the of glucose from the to interstitial is also by the for the to to and the use of for of the during of the into a glucose performance also may be by factors as and and used to the accuracy of CGM systems the between readings and BG by the as and error is the most used to the performance of CGM systems. Of note, has and use as the performance for CGM systems must be The the the CGM readings are to the glucose to clinical of the between the and the glucose accuracy to a higher of results in A and to with each generation of CGM sensors and systems. For most available CGM systems, the accuracy in clinical trials with 99% of glucose readings within the error A and It should be that in the CGM may higher than during Unlike BG meters for CGM, the accuracy have not been and there are no standards in the approval of CGM systems, particularly in to the of clinical data demonstrating the accuracy in the use as well as and to this the has a for CGM systems, as with additional accuracy of this device to with of diabetes management including insulin systems, insulin and BG and interstitial fluid including may interfere with CGM This can result in falsely high or low glucose In therapeutic of can glucose readings with glucose meter at a dose of can falsely glucose in CGM at may glucose readings, and at may falsely higher CGM readings may also be by of and The of substances on glucose depends on technology. CGM systems that use enzymatic electrochemical sensors to measure glucose concentrations to be more to than systems using to measure In for the long-term only and significant in within therapeutic as and available over the for and may be in combination or to persons with diabetes not that are from substances can be most significant for persons using CGM data confirmatory measurements of capillary BG or for those using CGM data to insulin in systems. CGM should be aware of systems may be by and test with a glucose meter do not a CGM The latest of systems (i.e., and all available are factory-calibrated, that using glucose measurements are not This and and a significant of error from is performed conditions during the For is for if CGM readings and results from capillary BG readings do not well over a of For generation CGM sensors that on (i.e., BG readings from a meter into the CGM the by Typically, the is performed of the and a of is 12 For these systems, are essential to the accuracy and The times to are the interstitial fluid glucose is in with the capillary glucose levels are least to be before before before insulin on the glucose levels are can lead to if at the of the has a falsely reduced or for by substances or systems for use, the glucose results needed to be by capillary SMBG before (e.g., insulin Along with significant improvements in accuracy, more and more sensors have approval for use, that is, and insulin are on CGM have shown that the of is safe for use of and most CGM systems this the T1D Exchange BG provided evidence of the and of non-adjunctive sensors and CGM, have and approval for non-adjunctive use in persons aged 2 years and The Glucose Diabetes have and approval for treatment in persons aged and The is for use from the age of years. testing may be recommended hypoglycemia, if glucose is and especially if are not with the of CGM CGM systems systems use for children with T1D was with only in with The clinical no overall with CGM use in the age years and related to in these A all age the was used and generation systems more that use of is to in both children and adults with T1D on the population are seen in of HbA1c concentrations, increased reduced (including and reduced glucose There is now evidence that improvement in is in of insulin therapy and studies have shown that to use of is with HbA1c a higher of people achieving ISPAD HbA1c and episodes of in children and This on HbA1c has also been seen in a that a of HbA1c in young children during the in with the use of and from registries improvement of T1D glycemic in children, adolescents, and In studies have not shown a number of in people using data from people with T1D aged years from and in the DPV and a in during the year of CGM data from observational studies in children and adolescents, irrespective of insulin early of CGM within year of T1D is with and more glucose using the non-adjunctive systems have shown on both HbA1c levels and in adolescents and young The of a that increased with this data from observational studies with population aged years have a of HbA1c levels and with use of from in young children have the results of studies from adolescents and young data from observational studies that CGM can be used successfully in children a more recent of non-adjunctive in young children age not a significant improvement in there was a in the of seen with capillary BG measurements over 6 data from the National that the use of CGM was well by children and that a was observed in glucose systems few have been using and only in adolescents and young The on and adults with HbA1c at It that use reduced in hypoglycemia, reduced glucose and improved to to to including significantly reduced in of HbA1c observed in a of the in adults with T1D with However, the of this technology in those with In a in aged to years with HbA1c not demonstrate in HbA1c levels using to this population increased testing and a higher with from observational clinical studies in children aged years at have shown and to SMBG use to to has been in age more pronounced in children 12 and to and is with glycemic and though not with of in studies all performed using systems for hypo- and using systems with and improved accuracy are In real-world data studies have also shown increased in observational in children and adults using data from individuals in the diabetes registry that was with significant in HbA1c with the in those with highest HbA1c and children years of episodes also in among those at higher for requiring a in was also A real-world year of of in and with the use of CGM In recent years, studies and systems have been including observational studies in children and and adults with and in superiority of over in of improved and reduced of in However, the number of studies and the number of participants particularly in children and generation devices CGM use from diabetes from diabetes has been shown to long-term glycemic in individuals with Early of CGM among children with diabetes was with a HbA1c at 12 to those not improvement in HbA1c over a was seen CGM was in the year T1D to no CGM use or CGM the often by has been a of interventions for persons with T1D to of long-term diabetes related There are several studies the of more CGM and systems in in the the role of CGM and in clinical trials as is CGM be used to glycemic in studies on diabetes or There also be a role for CGM in the monitoring of people at high of T1D considerations and and in CGM use a to CGM uptake and long-term use, as glycemic are only observed if the device is many aspects of CGM use of and CGM device skin and data is to safe and effective use of this and are as essential to overcome barriers to CGM use and as are continuously is also recommended to to and their glucose In is to and to and educational and to CGM use should also be provided to of children with including 2 provides an of the aspects to at CGM (Table and For sensors requiring of and times to them and use at can be over data can be in glycemic with which a for and their has to be effective in both the and early of Limited data on the efficacy of in during to In a in adults with the use of was to in and during The use of and in glucose in to glycemic fluctuations during and the use of for glucose the to with to the in glucose and the A recent recommends glycemic ranges during and to the age the type of the for and in with the However, these a that to be for the and CGM remote monitoring also the for to in of glycemic with or to nocturnal in For more information on in children and adolescents with please refer to the ISPAD 2022 Consensus Chapter on in children and adolescents with diabetes. CGM and skin skin by skin or to or device a to long-term CGM use, especially in young of from CGM use in clinical trials low with per of However, there to be between and observational on skin related to CGM use are more frequent with the long-term use of sensors and the availability of devices with skin conditions the device or the at CGM at the application evidence of sensors and as factors for skin including The is available by most devices which can for and accurate of the of devices to skin device skin proper and of skin In to the of may the of skin to frequent For more information on skin related issues, please refer to the ISPAD 2022 Consensus Chapter on and conditions in children and adolescents with type diabetes. monitoring CGM systems have the to glucose data to the and for remote monitoring, are to a CGM and on their as and monitoring of CGM has been to several psychosocial in of children with including quality of reduced and improved may have increased in their children with (e.g., their of the glucose levels and from with remote CGM monitoring of CGM data in the may a to diabetes management between the with and of has been with in children with especially during the The to CGM data has been shown to nocturnal in with The of by the to CGM data and real-time for glucose and with glucose to overall However, can also of remote monitoring of CGM For with diabetes may have the of by their in of the remote might in as falsely low to This the need for diabetes management with regarding and should on remote monitoring of glucose data and This is particularly in adolescents may in diabetes management can from the of their and CGM is a for real-time data in the of that professionals have glucose data for This professionals to review and glucose data to on therapy during that CGM use has become to effective remote diabetes care delivery, as data can between and the diabetes team. The in early the widespread adoption of and remote person diabetes among those to person observational studies regarding the of CGM during the However, evidence demonstrating the of CGM data in clinical in with diabetes are an well the achieve the from CGM, persons with T1D and may need more frequent with the diabetes care to to the widespread adoption of for people with diabetes and of that is, remote availability of glucose data for review by people with diabetes and their including and to diabetes technology major to ISPAD for more availability and to diabetes technology for all people with diabetes. and continuous use of diabetes devices and are with psychosocial and factors are defined as and that an both of (e.g., and on (e.g., The on psychosocial factors in to diabetes device and technology use has out of the in these factors diabetes management and For is well that personal and with are with management and psychosocial factors as diabetes and are in with diabetes and often lead to management and the current of the between psychosocial factors and CGM use be ISPAD guidelines on the psychosocial care of and the Diabetes guidelines for the psychosocial care of people with that to the psychosocial of all and their is refer to ISPAD 2022 Consensus Chapter 15 on care of children and adolescents with type diabetes. CGM, the use of devices and provides additional advice for and of diabetes devices For in a of of in the and as for in the and of of of the and the barriers to Of note, children and adolescents from in that to their immediate (e.g., and most the accuracy and that systems glucose levels and for long-term these of and on quality of and are with In the the the as the a person and related to device This can be for and device use. In the current evidence to psychosocial and quality of from using CGM and devices as systems. to barriers to technology use are However, more in the pediatric population is needed on the to barriers to device and technology use and This in effective and and as a for to the and of the past 30 years, glucose monitoring has from urine glucose testing and fingerstick capillary BG measurements to continuous glucose monitoring systems using interstitial technology. Along with significant improvements in CGM technology (including accuracy, device size, and wider availability of CGM systems to by and in more parts of the and of their application to SMBG in CGM has become standard of care for people with T1D in many CGM technology is at the of diabetes management. CGM in particular as of with readings between and and 10 have been as clinical and that or HbA1c for a of people with diabetes ISPAD 2022 Consensus Chapter on or of CGM data to and remote of the This has been and to be instrumental in care during the and significant has been in insulin in the of a ISPAD 2022 Consensus Chapter on With the of CGM sensors for use, as if SMBG has to a in glucose However, has an Even of systems with CGM have to capillary BG measurements in that is, if readings and personal do not to hypoglycemia, to do if readings are not accurate, and no CGM data are Of people do not have to CGM on SMBG CGM devices and sensors are and may not be available in many may also be these devices to become more widely available and by both and is ISPAD for increased availability of CGM for children, adolescents, and young adults with diabetes. CGM should be in all children, adolescents, and young adults with T1D as as This chapter has evidence on glucose monitoring technology in children, adolescents, and young on their use and practical advice regarding their has been Since this is a area of and further and are to be from and has on an of has as an for and is a to and has for on for and and as a for and has for on and and to from and have no to