# Abstract

 

## OBJECTIVE Continuous glucose monitoring (CGM) has been demonstrated to improve glycemic control in adults with type 1 diabetes but less so in children. We designed a study to assess CGM benefit in young children aged 4 to 9 years with type 1 diabetes. 

## RESEARCH DESIGN AND METHODS After a run-in phase, 146 children with type 1 diabetes (mean age 7.5 ± 1.7 years, 64% on pumps, median diabetes duration 3.5 years) were randomly assigned to CGM or to usual care. The primary outcome was reduction in HbA~1c~ at 26 weeks by ≥0.5% without the occurrence of severe hypoglycemia. 

## RESULTS The primary outcome was achieved by 19% in the CGM group and 28% in the control group (*P* = 0.17). Mean change in HbA~1c~ was −0.1% in each group (*P* = 0.79). Severe hypoglycemia rates were similarly low in both groups. CGM wear decreased over time, with only 41% averaging at least 6 days/week at 26 weeks. There was no correlation between CGM use and change in HbA~1c~ (*r~s~* = −0.09, *P* = 0.44). CGM wear was well tolerated, and parental satisfaction with CGM was high. However, parental fear of hypoglycemia was not reduced. 

## CONCLUSIONS CGM in 4- to 9-year-olds did not improve glycemic control despite a high degree of parental satisfaction with CGM. We postulate that this finding may be related in part to limited use of the CGM glucose data in day-to-day management and to an unremitting fear of hypoglycemia. Overcoming the barriers that prevent integration of these critical glucose data into day-to-day management remains a challenge. # RESULTS Between January 2009 and December 2010, the trial randomized 146 children aged 4.0--9.9 years (7.5 ± 1.7 years [mean ± SD]) who had a median duration of type 1 diabetes of 3.5 years (interquartile range 2.2--5.2). The majority of participants was non-Hispanic white and was using insulin pumps. Baseline characteristics were well balanced between the two treatment groups ([Table 1](#)). ::::table-wrap

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Baseline characteristics of the participants
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![](<>):::: HbA~1c~ decreased by a mean of 0.2 ± 0.7% (measured with a DCA instrument) during the run-in phase. Mean HbA~1c~ at the time of randomization (measured by central laboratory) was 7.9 ± 0.8% in each treatment group. Total daily insulin dose averaged 0.8 ± 0.2 units/kg/day in both treatment groups at baseline and at 26 weeks. The 26-week primary outcome visit was completed by 69 of 74 participants (93%) in the CGM group and 68 of 72 (94%) in the control group, with 5 and 4 participants in the two treatment groups, respectively, discontinuing study participation prior to completion of the 26-week visit ([Supplementary Fig. A1](#)). The overall completion rates for the six follow-up visits and the six protocol-specified phone calls were 93% and 94% in the CGM and control groups, respectively. Among the 74 participants in the CGM group, 10 (14%) were provided with a Paradigm CGM device and 64 (86%) with a Navigator CGM device. No participants in the control group self-initiated CGM prior to completing the 26-week visit. 

## Glycemic control The primary outcome of a decrease from randomization to 26 weeks in HbA~1c~ ≥0.5% with no severe hypoglycemic events occurred in 13 of 69 (19%) participants in the CGM group and 19 of 68 (28%) in the control group (*P* = 0.17). Mean change in HbA~1c~ was similar between groups (−0.1 ± 0.6 in each group, *P* = 0.79) ([Supplementary Fig. A2](#)). Other HbA~1c~ outcomes at 26 weeks showed similar comparability between treatment groups ([Table 2](#)). Outcomes in subgroups based on age, sex, race/ethnicity, parent education level, insulin modality (pump vs. MDIs), baseline HbA~1c~, or BMI also did not differ between groups and are shown in [Supplementary Table A1](#). ::::table-wrap
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Outcomes at 26 weeks\*
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![](<>):::: Glycemic outcomes measured with CGM showed no significant differences between treatment groups (considering the multiple outcomes assessed) with respect to percent of values within, above, and below the target range ([Table 2](#) and [Supplementary Table A2](#)). Participants in both groups had glucose values >250 mg/dL for >20% of the day. 

## Hypoglycemia and other adverse events Three participants (4%, three total events) in the CGM group and five participants (7%, six total events) in the control group experienced at least one severe hypoglycemic event, with no significant differences comparing treatment groups (incidence rate = 8.6 and 17.6 per 100 person-years, respectively; *P* = 0.80) ([Table 2](#)). At 26 weeks, both groups had CGM glucose values ≤60 mg/dL for \<1% of the day. There were no cases of diabetic ketoacidosis and no serious adverse events attributable to the study interventions, including no serious skin reactions. 

## Frequency of sensor use in the CGM group A total of 63 (91%) of 69 participants who completed the 26-week visit were wearing a sensor on at least 1 day a week at the end of 26 weeks. The amount of CGM sensor wear decreased during the 26 weeks of the study (*P* < 0.001) ([Fig. 1](#)), with only 41% averaging at least 6 days/week of wear in month 6. The amount of sensor wear in month 6 did not vary with age overall (*r* = −0.07) and was not associated with baseline HbA~1c~ (*r* = −0.02). <figure> <p><img src="" /></p> <figcaption>Sensor use during the 26 weeks of the trial. Each box represents the number of hours per week of CGM sensor glucose data averaged over 4 weeks. The top and bottom of the boxes represent the 75th and 25th percentiles, respectively; the horizontal line within each box represents the median; and the black dot represents the mean. For participants who dropped from the trial, sensor use was considered to be zero after the day of dropout. Data were considered missing when downloaded glucose data were not available for a 4-week period. *Sensor download was unavailable due to device issue for one subject in 22–26 weeks.</figcaption> </figure> There was no association between change in HbA~1c~ from baseline to 26 weeks and the overall amount of CGM sensor wear during the entire 26 weeks (Spearman *r~s~* = −0.09, *P* = 0.44) or during month 6 (Spearman *r~s~* = −0.11, *P* = 0.37). However, the 28 participants who wore a sensor ≥6 days/week during month 6 tended to have a slightly greater reduction in HbA~1c~ compared with the 41 participants who wore a sensor less frequently (mean change from baseline to 26 weeks −0.3 ± 0.7% vs. 0.0 ± 0.5%, *P* = 0.01; 25 vs. 15% with a reduction in HbA~1c~ ≥0.5% without a severe hypoglycemia event, *P* = 0.33). Among those wearing a sensor ≥6 days/week in month 6, the median percentage of glucose values in the target range of 71--180 mg/dL was 51%, with 38% >200 mg/dL, 16% >250 mg/dL, and 0.3% ≤60 mg/dL compared with 43, 44, 23, and 0.4%, respectively, in those wearing a sensor less frequently. 

## Quality of life assessments At 26 weeks, there were no significant differences between treatment groups on the Hypoglycemia Fear or the PAID questionnaire survey scores ([Table 2](#) and [Supplementary Tables A3 and A6](#)). However, scores on the Blood Glucose Monitoring System Rating Scale were indicative of fewer problems/concerns perceived by the CGM group compared with the control group ([Table 2](#) and [Supplementary Table A5](#)). On the CGM Satisfaction Scale at 26 weeks ([Table 3](#) and [Supplementary Table A4](#)), parents generally reported a high degree of satisfaction with CGM, with an average item score of 3.9 and 86% of scores ≥3.5 (on a 5-point Likert-type scale, with 3 being neutral). Mean item scores were more favorable than neutral (>3.0) on all 43 items. Scores on the Benefits of CGM subscale tended to be slightly higher than scores on the Lack of Hassles of CGM subscale (mean 4.1 ± 0.4 vs. 3.9 ± 0.6, respectively). It is particularly noteworthy that >90% of parents responded that use of CGM makes adjusting insulin easier, shows patterns in blood glucose not seen before, and makes them feel safer knowing that they will be warned about low blood glucose before it happens. No one responded that he or she would not recommend CGM for other children with type 1 diabetes. ::::table-wrap
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CGM Satisfaction Scale scores* at 26 weeks (*N* = 69)
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Extracted trial result:
Outcome: PAID questionnaire fear of hypoglycemia (continuous)
Intervention: Real-Time Continuous Glucose Monitoring
Comparator: Control
Intervention group size: 69
Comparator group size: 68
Notes: Numerical values in Table which is a graphic