Psychological Reactions Associated With Continuous Glucose Monitoring in Youth

638109DSTXXX10.1177/1932296816638109Journal of Diabetes Science and TechnologyPatton and Clements research-article2016 Special Section Psychological Reactions Associated With Continuous Glucose Monitoring in Youth Journal of Diabetes Science and Technology 2016, Vol. 10(3) 656 661 2016 Diabetes Technology Society Reprints and permissions: sagepub.com/journalspermissions.nav DOI: 10.1177/1932296816638109 dst.sagepub.com Susana R. Patton, PhD, CDE 1,2 and Mark A. Clements, MD, PhD 3,4 Abstract Glucose monitoring is prerequisite to all other diabetes self-care behaviors and helps patients to reduce their risk for diabetes-related complications due to elevated glycemia. Because of the amount of information available and the ability to deliver glucose results in real-time, continuous glucose monitoring (CGM) has the ability to improve on self-monitoring blood glucose. However, epidemiologic data demonstrate slow uptake of CGM by patients, especially among youth. Several new diabetes therapies rely on CGM for feedback on patients glucose levels to optimize treatment (eg, the low-glucose suspend insulin pump) and there are new technologies currently in development that will also need this information to work (eg, the artificial pancreas). To help patients to realize the potential benefits of these new treatments, it is essential to explore patients psychological and behavioral reactions to CGM and then target device enhancements and/or the development of behavioral therapies to minimize negative reactions and to improve patients CGM adoption rates. Limited research is available examining the psychological and behavioral reactions of CGM use in youth exclusively, but there are more studies examining these reactions in mixed samples of youth, parents, and adults. The purpose of this review is to summarize the available literature examining psychological and behavioral reactions to CGM use in young people with diabetes and to highlight how the results of past and future studies can inform device updates and/or behavioral intervention development to minimize barriers. Keywords continuous glucose monitoring, psychology, psychological adjustment, burden, quality of life, intervention Young people with diabetes face a demanding daily treatment regimen, a cornerstone of which is regular blood glucose monitoring. 1 Blood glucose monitoring persists as an essential component of modern treatment because it provides the information patients need to effectively perform all other diabetes self-care behaviors. 1,2 In addition, diabetes care providers rely on these data to optimize insulin therapy and to determine emergency treatments. 1,2 The invention and uptake of continuous glucose monitoring (CGM) into daily diabetes treatment has, in many ways, enhanced glucose monitoring by providing real-time alerts for out-of-range glycemic levels and a significantly greater volume of glucose data for pattern analysis. 2 In turn, studies show a dose effect for CGM which, when worn consistently, can lead to improved glycemic control and a reduction in episodes of severe hypoglycemia. 3,4 However, the literature also shows that many youth do not use CGM as part of their daily diabetes treatment or use it only infrequently. 3 Data from the Type 1 Diabetes (T1D) Exchange suggest that only 4-6% of children less than 18 years old use CGM compared to 21% of adults. 3 Moreover, among the reported CGM users, the same study found that youth reported a lower median number of days of CGM use compared to adults. 3 Studies have identified both positive and adverse psychological effects related to CGM use, 5-11 which may impact its rate of adoption. Notably, the ability to implement several new technologies (ie, low-glucose suspend insulin pumps, real-time/retrospective cloud-based data sharing, artificial pancreas) will rely on CGMs to provide the required glucose values. As such, it is essential that we continue to explore the factors related to patients CGM use. This review summarizes the available literature examining psychosocial and behavioral reactions to CGM use in youth with diabetes, identifying challenges and gaps in this literature, as well as highlighting areas where the current knowledge could directly inform device enhancements or behavioral intervention development. Because there are 1 University of Kansas Medical Center, Kansas City, KS, USA 2 Center for Children s Healthy Lifestyles and Nutrition, Kansas City, MO, USA 3 Children s Mercy Kansas City, Kansas City, MO, USA 4 University of Missouri Kansas City, Kansas City, MO, USA Corresponding Author: Susana R. Patton, PhD, CDE, University of Kansas Medical Center, MS 4004, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. Email: spatton2@kumc.edu

Patton and Clements 657 relatively few studies in this area with youth-only samples (<18 years old), we have also included studies reporting results from mixed samples of adolescents, parents, and adults. Finally, we included studies that used either real-time or retrospective CGM devices to provide a broader review of the potential psychosocial and/or behavioral reactions to CGMs. Methods Articles were identified through 1 of 2 databases (PsycINFO and PubMed). Keywords for the search included diabetes mellitus, continuous glucose monitoring, psychological adjustment, quality of life, self-efficacy, burden, anxiety, depression, and mood. In the first search pass, 248 articles were identified. Next, duplicate articles (n = 10) were excluded. Articles were also excluded if they did not focus on patients CGM use (n = 47), if they only reported data for adults (n = 20), if they did not provide some measure of patients psychosocial and/or behavioral reaction to CGM use (n = 71), and if they met all 3 of these exclusion criteria (n = 86). Thus, a final sample of 14 articles was selected for review (see Table 1). Results Impact of CGM on Quality of Life (QOL) Within the current literature, 6 studies recruited youth-only samples and 8 studies recruited mixed samples. A change in QOL was the most commonly examined psychosocial reaction to CGM use in patients. The largest study, recruiting 451 children and adults with T1D, 12 examined both generic and diabetes-specific QOL changes using either the Pediatric Quality of Life Inventory (PedsQL) 13,14 in participants less than 18 years old and their parents, or the Problem Areas in Diabetes (PAID) 15 scales and the Social Functioning Health Survey (SF-12, version 2) 16 in participants older than 18 years. Patients in this large trial were randomized to either receive CGM or continue glucometer monitoring; QOL was assessed at baseline and at 26 weeks. 12 Among youth and parents, PedsQL scores were high at baseline and remained high at 26 weeks, resulting in no change. In contrast, a 1.4 point improvement on the Physical Component subscale of the SF-12 was found among adult CGM users (P =.03), but the PAID and the Mental Component subscale of the SF-12 did not change. 12 In 4 other randomized clinical trials, no differences in QOL were found among youth and parents. 9,17-19 However, in all cases, youth and parents started with high QOL scores and maintained these scores regardless of CGM use. In addition, at least 1 study may have been underpowered to detect differences in QOL. 17 In contrast, improved QOL was found for a subset of adolescents and adults who were either randomized to receive an algorithm to guide their CGM use at initiation (immediate treatment) or after 16-weeks (delayed start) of CGM use. 20 Specifically, improved QOL was reported in the immediate treatment group when compared to the delayed start group at 16 weeks and again at 32 weeks, suggesting better guidance in CGM therapy could be a factor underlying perceived QOL. 20 Likewise, improved QOL has been found in youth and parents who participated in 1 of 2 cohort studies. 6,11 In the first of these studies, improved QOL was reported by 78% of youth after a 4 week trial of real-time CGM regardless of change in HbA1c level. 6 However, in the second trial, only adolescents who experienced an improvement in HbA1c after 4 weeks of real-time CGM use reported better QOL. 11 Results from both studies are limited because the studies lacked a control group, the samples were motivated to use CGM at the outset, and because they both used a single question to assess QOL versus a validated measure. In addition, in the case of the second trial, it not clear if youth knew the results of the HbA1c before reporting on their QOL at follow-up, but surely it is possible the timing of such knowledge could have impacted their reporting. Nonetheless, collectively, the results from all of the studies examining QOL changes as a result of CGM use suggest that, at minimum, there is no change. Associations Between CGM and Fear of Hypoglycemia (FOH) Another psychological reaction commonly studied in relation to CGM use was FOH. This variable was included as part of 3 large randomized clinical trials. 12,18,19 In these studies, FOH was assessed either by the Hypoglycemia Fear Survey 21 or the Diabetes Worry Scale. 22 Again, the study results were mixed. Adult patients assessed after 26 weeks of CGM use reported reduced fear, while no change was found for parents and youth. 12,19 Likewise, there was no change in general diabetes worry for parents and youth after 6 months of CGM use. 18 Only 1 prior cohort study examined for FOH. 6 In this study, fear was assessed after 1 month of real-time CGM use based on parents responses to 2 survey items: Wearing the sensor helped prevent hypoglycemic reactions and I/my child was/were not as worried about having hypoglycemia reactions while wearing the sensor. In all, 88% of parents reported feeling better able to prevent hypoglycemia when using CGM and 83% of parents reported reduced FOH as a result of CGM use. 6 Limitations of that study include the lack of randomization, lack of a control group and the use of a nonvalidated measure of FOH, which collectively reduce the generalizability of the study. CGM and Other Psychological Changes Individual studies have looked at other potential psychological changes. As part of a larger randomized clinical trial, Markowitz et al 8 examined for group differences in anxiety, depression, and conflict for youth, parents, and adults

658 Journal of Diabetes Science and Technology 10(3) Table 1. Study Characteristics and Results Regarding Psychological Reactions to CGM Use in Youth and Mixed Samples of Youth, Parents, and Adults With Type 1 Diabetes. Source Sample size Age RCT Results Youth only Chase et al 17 11 10-17 years Yes QOL was comparable for CGM users and controls DirecNet Study Group 18a 200 7-18 years Yes Generic and diabetes-specific QOL and parental FOH were comparable for CGM users and controls Cemeroglu et al 6 43 3-25 years No Reduced FOH, improved QOL, and greater ease in T1DM related to CGM use reported JDRF Continuous Glucose Monitoring Study Group 12 213 <18 years Yes High satisfaction reported among CGM users and their parents; QOL, FOH, and distress were comparable for CGM users and controls Mauras et al 19 146 4-9 years Yes Parents reported high satisfaction with CGM; QOL, FOH, and distress were comparable for CGM users and controls Glowinska-Olszewska et al 11 40 10-18 years No Improved QOL after CGM use Mixed samples DirecNet Study Group 18a 451 7-18 years; > 18 years Yes Generic and diabetes-specific QOL and parental FOH were comparable for youth CGM users and controls; adult CGM users reported lower FOH and better social functioning versus adult controls Jenkins et al 20 60 13-70 years Yes Better QOL for patients who received an algorithm to guide their CGM use at the time they started CGM versus 16 weeks into CGM use Ramchandani et al 23 58 <26 years No CGM users reported greater perceived ease of T1DM, better hypoglycemia detection, and improved control; reported hassles were pain and nuisance alarms Tansey et al 7 624 >18 years; 8-18 years Yes CGM users reported greater perceived ease of T1DM and better hypoglycemia detection; reported problems were pain, alarms, and body issues Markowitz et al 8 51 8-17 years Yes Family conflict and FOH were comparable for CGM users and controls; CGM users reported greater negative affect and poorer communication, CGM users reported greater anxiety and depressive symptoms than controls Hommel et al 9 153 6-70 years Yes QOL and FOH comparable for CGM users and controls; CGM users missed fewer school days and parents reported less burden than controls Landau et al 25 13 <17 years; >18 years No Parents had more night time awakenings and greater total wake time after CGM initiation versus before CGM Pickup et al 5 100 >18 years No Positive psychological reactions were reduced stress/ anxiety, greater peace of mind, and a greater sense of normalcy; negative reactions were feeling overwhelmed by the data, children feeling more stigmatized, and increased anxiety/burden due to greater awareness of glucose levels CGM, continuous glucose monitoring; FOH, fear of hypoglycemia; QOL, quality of life; T1DM, type 1 diabetes mellitus. a These reference the same study; presentation of the study s data allows some results to be reported for youths only versus the full sample of adults, youths, and parents. participating in the Juvenile Diabetes Research Foundation CGM study. Results reflected no differences in family conflict despite CGM use. However, all patients using CGM reported greater negative affect and poorer communication around blood glucose levels than control patients, and youth using CGM reported greater general anxiety and greater depressive symptoms than control youth. 8 Two other studies reported on perceived satisfaction to CGM use. 7,23 In 1 study, the Continuous Glucose Monitoring Satisfaction Scale 24 was used and results found overall high perceived satisfaction across adults and youth, with particular benefits noted for ease of diabetes management and better detection of hypoglycemia. 7 In the other study, a nonstandard questionnaire was used, but the results were largely the same,

Patton and Clements 659 with the majority of CGM users reporting perceived benefits related to the quantity of glucose data available and the opportunity for better control. 23 Finally, in a qualitative study of 100 adults and children, positive psychological themes identified included improved ease of management, reduced stress and anxiety, greater peace of mind, and a greater sense of normalcy. 5 Negative Reactions to CGM A smaller set of studies has examined for negative behavioral and psychological reactions to CGM use. Landau et al 25 studied changes in parents sleep after initiating CGM in their child. Interestingly, while parents perceived no changes in their sleep using the questionnaire, their sleep diaries and actigraphy revealed more nighttime awakenings and longer total wake times for parents after starting CGM, suggesting that parental sleep maybe adversely impacted by CGM. Three other studies reported perceived hassles and problems related to pain, nuisance alarms, and body issues. 5,7,23 Moreover, negative qualitative themes were also identified from patient interviews, with patients commonly reporting feeling overwhelmed by the volume of data, youth reporting feeling more stigmatized for their diabetes when wearing a CGM, and parents reporting greater anxiety as a result of their greater awareness of their child s glucose levels. 5 Discussion The use of CGM by individuals with diabetes is associated with psychological benefits, but also some burdens. Potential benefits include improved QOL and decreased FOH, although studies show mixed results for randomized clinical trials versus cohort studies and for youth and adults. 6,9,11,12,17-20 Studies of adolescents and adults have nearly universally reported high perceived satisfaction for CGM use, with specific benefits reported related to ease of diabetes management, better detection of hypoglycemia, and better glycemic control. 5,7,23 In contrast, reported burdens of CGM use include pain and body issues, problems with communication and feeling overwhelmed by the volume and complexity of the glucose data available, 5,23 and concerns related to the accuracy of CGM compared to glucometer readings. 26 Increased anxiety among adolescents and parents, 8 and poorer parental sleep 25 have also been observed. Despite its benefits, the uptake of CGM into daily selfmanagement has been slow, especially among youth. 3 This indicates that the burden of CGM therapy remains unacceptably high for many. Manufacturers can reduce the burden of CGM by learning from existing data to iteratively improve CGM devices. First, manufacturers can reduce the pain and inconvenience associated with CGM use by reducing the length and width of glucose biosensors, as well as the skin footprint of CGM devices. Likewise, alternative adhesives targeted to individuals with atopy or sensitive skin could reduce pain and other adverse skin effects. 27 Finally, device makers can increase users confidence in the accuracy of CGM data by transparently reporting accuracy metrics or alternatively, developing precalibrated CGM devices to eliminate the need for glucometer data during daily CGM use. Presently, a factory-calibrated flash glucose monitoring device 28 is currently being developed and deployed. Several device enhancements could also increase the perceived benefits of CGM. First, device makers could create and validate simplified data visualization tools to help patients better understand their glucose data. Manufacturers could use the results from existing studies to develop ondemand diabetes education materials related to CGM use and pattern management. Moreover, if these materials could be incorporated into mobile medical applications, this format could maximize accessibility. Finally, device makers could promote data portability between devices and web-based data visualization tools, mobile medical applications, and electronic health record systems, thereby making it easier for patients to share data with their diabetes care providers and receive clinician feedback regarding pattern identification, insulin adjustments, and daily decision making. Yet, existing studies must be interpreted in the context of certain limitations. Several studies noted very high levels of QOL and low levels of FOH among participants at baseline. As such, ceiling and floor effects likely reduced the amount of change possible due to CGM use. Some studies recruited smaller samples, leading to the possibility that they were underpowered to detect differences. Studies used a variety of measures, including nonstandard measures, which may limit the ability to make comparisons across studies. Previous studies did not examine the impact of common negative reactions to CGM (eg, pain, body issues, or data overload ) on patients psychological health, including anxiety, depression, or sleep. Finally, although we applied the rule that youth were <18 years old in our review, studies varied significantly with respect to the ages of their participants and did not apply a consistent definition of youth or adult, which could also affect generalizability. A number of critical areas remain poorly studied and need to be a focus of future research. For example, future studies should focus on alternative psychological reactions to CGM, such as patient self-efficacy and resilience. Research is needed examining the contribution of component features of CGM (eg, real-time versus retrospective data visualization tools, alarms, and specific threshold settings used to trigger alarms) to its overall efficacy and acceptability. We need research investigating the degree to which behavioral health interventions can increase efficacy of, and satisfaction with, CGM. We need studies that examine patients reactions to CGM when it is used as part of a multicomponent diabetes management system, such as sensor-augmented pump therapy, 29 sensor-augmented pump therapy with low-glucose suspend, 30 hybrid closed loop therapy, 31 fully automated closed loop therapy with

660 Journal of Diabetes Science and Technology 10(3) insulin, 31-33 or bihormonal artificial pancreas therapy with glucagon and insulin. 34 And we need research examining the degree to which novel strategies such as CGM holidays (eg, cycling CGM therapy on and off ) can enhance patient engagement CGM efficacy. In summary, CGM is a promising technology with the capacity to significantly improve glycemic control among individuals with diabetes. Although adoption and long-term engagement with the therapy remain problematic, future research and future device enhancements can help to maximize the benefit and minimize the burden of CGM therapy. Abbreviations CGM, continuous glucose monitoring; FOH, fear of hypoglycemia; HbA1c, glycated hemoglobin; PAID, Problem Areas in Diabetes; PedsQL, Pediatric Quality of Life Inventory; QOL, quality of life; SF-12, Social Functioning Health Survey; T1D, type 1 diabetes. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded in part by grants R01 DK100779 and DP3 DK108211 from the National Institute of Diabetes and Digestive and Kidney Diseases and R21 HD081502 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. References 1. Chiang JL, Kirkman MS, Laffel LM, Peters AL. Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes Care. 2014;37(7):2034-2054. 2. Rewers MJ, Pillay K, de Beaufort C, et al. Assessment and monitoring of glycemic control in children and adolescents with diabetes. Pediatr Diabetes. 2014;15(suppl 20):102-114. 3. 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