Continuous glucose monitoring study does not demonstrate benefit in children and adolescents

The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med 2008;359:1464-76 

Question Among patients with type 1 diabetes mellitus, does the use of continuous glucose monitoring result in improved glycemic control?

Design Randomized, controlled trial.

Setting Multiple centers in the United States.

Participants A total of 322 adults and children who were already receiving intensive therapy for type 1 diabetes.

Intervention Continuous glucose monitoring or a control group performing home monitoring with a blood glucose meter.

Outcomes Change in the glycated hemoglobin level at 26 weeks.

Main Results The changes in glycated hemoglobin levels in the 2 study groups varied markedly according to age group (P = .003), with a significant difference among patients 25 years of age or older that favored the continuous-monitoring group (mean difference in change, −0.53%; 95% confidence interval [CI], −0.71 to −0.35; P < .001). The between-group difference was not significant among those who were 15 to 24 years of age (mean difference, 0.08; 95% CI, −0.17 to 0.33; P = 0.52) or among those who were 8 to 14 years of age (mean difference, −0.13; 95% CI, −0.38 to 0.11; P = .29). Secondary glycated hemoglobin outcomes were better in the continuous-monitoring group than in the control group among the oldest and youngest patients but not among those who were 15 to 24 years of age. The use of continuous glucose monitoring averaged 6.0 or more days per week for 83% of patients 25 years of age or older, 30% of those 15 to 24 years of age, and 50% of those 8 to 14 years of age. The rate of severe hypoglycemia was low and did not differ between the 2 study groups; however, the trial was not powered to detect such a difference.

Conclusions Continuous glucose monitoring can be associated with improved glycemic control in adults with type 1 diabetes, but was not effective in children and adolescents.

Commentary This is the largest, prospective, individually randomized unblinded controlled trial of continuous glucose monitoring (CGM). Use of CGM was associated with significantly improved glycemic control in adults with type 1 diabetes, but not children or adolescents. Between-group A1C levels fell by a mean of 0.53% in adults. Nonsignificant benefit of CGM was observed in subjects who were 8 to 14 years of age, and no benefit was observed among subjects who were 15 to 24 years of age. Why didn't children and adolescents benefit? The reasons might be related to adherence and to the study's method for randomization. Use of CGM is a tool for directing behavior on the basis of glucose levels. Adherence to a behavioral intervention is necessary for the intervention to be successful.1 Adherence alone might account for the ranking of results between adults with the greatest compliance (80%) and greatest benefit, compared with children with the second-best compliance (50%) and second best results, and adolescents with the least compliance (33%) least benefit. The study used individual randomization, which is appropriate for a blinded trial, but in an unblinded trial of a behavioral intervention, cluster randomization of study sites is often used to prevent contamination of control subjects from knowledge of the intervention.2 If control subjects learn about benefits of using CGM at the investigator's office, then they might monitor their glucose more frequently and artifactually improve their control. This behavior could improve the A1C outcome for controls and wash out the between-group benefit of the CGM intervention. Indeed, in this study the children and adolescent control subjects both had at least a 0.21% improvement in A1C, suggesting possible contamination of control subjects in this study.