A hybrid closed-loop system can deliver glucose levels in the target range at a higher percentage of time among children aged 2 years to younger than 6 years compared to standard-care, according to a study in the New England Journal of Medicine.
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Children aged 2 years to younger than 6 years with type 1 diabetes (T1D) have glucose levels in the target range for a greater percentage of time with a hybrid closed-loop system compared to standard-care insulin delivery involving a continuous glucose monitor, according to a study published in the New England Journal of Medicine.
In children younger than 6 years of age with T1D, treatment is challenging due to small doses of insulin, unpredictable food intake, and unscheduled exercise activity. Hybrid closed-loop therapy, or an artificial pancreas or automated insulin delivery, has been shown to improve glycemic control in youths and adults with T1D. According to study authors, 2 hybrid closed-loop systems are approved in the United States for children with T1D that are younger than 6 years.
The t:slim X2 insulin pump with Control-IQ Technology system (Tandem Diabetes Care) enables automated basal adjustments and bolus corrections delivered from an insulin pump every 5 minutes. The system was approved in the United States for use in adults and children 6 years and older; however, little is known about the use of the system in children younger than 6 years of age. To determine the safety and efficacy of this system, a multicenter, unblinded, parallel group, randomized, controlled Pediatric Artificial Pancreas (PEDAP) trail was conducted in pediatric diabetes centers at 3 US universities. Additionally, investigators included the option of virtual training in the use of the device and virtual trial visits.
To be eligible, patients had to be at least 2 years of age but younger than 6 years. They also must have received a T1D diagnosis at least 6 months before trial enrollment, received treatment with insulin for at least 6 months, have had a body weight of at least 20 lbs (9.1 kg), and received a total daily insulin dose of at least 5 units. Between April 28, 2021, and January 13, 2022, a total of 102 children were randomly assigned at a 2 to 1 ratio for the 13-week trial. Sixty-eight patients were assigned to the closed-loop group while 34 were assigned to the standard-care group. The standard-care group included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor.
The primary outcome of the study was the percentage of time that glucose levels were in the target range of 70 mg to 180 mg per deciliter, as measured by continuous glucose monitoring, according to authors. Secondary outcomes were the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes. Safety outcomes included the incidence of severe hypoglycemia, diabetic ketoacidosis, and other serious adverse events, according to the authors. Both groups had virtual or in-person trail visits at 2, 6, and 13 weeks after randomization, with telephone contacts at 1 and 10 weeks.
The mean (±SD) percentage of time that the glucose level was in the target range of 70 mg to 180 mg per deciliter (the primary outcome) increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group, with a mean adjusted difference (the value in the closed-loop group minus the value in the standard-care group) of 12.4 percentage points (95% confidence interval [CI] 9.5 to 15.3 [P < 0.001]).
Amid follow-up, the mean percentage of time the glucose level was in the target range between 6:00 am to 9:59 am was 67% in the closed-loop group and 56% in the standard-care group. From 10:00 pm to 5:59 am, the mean percentage of time the glucose level was in the target range was 74% in the closed-loop group and 56% in the standard-care group. The maximum between-group difference was observedat approximately 5:00 am.
According to authors, “Similar treatment effects favoring the closed-loop group were observed in the percentage of time that the glucose level was above 250 mg per deciliter (mean difference between the closed-loop group and the standard-care group, −5.4 percentage points; 95% CI −7.3 to −3.6 [P < 0.001), in the mean glucose level (mean difference, −17.7 mg per deciliter; 95% CI −23.2 to −12.2 [P < 0.001]), and in the glycated hemoglobin level (mean difference, −0.42 percentage points; 95% CI −0.62 to −0.22 [P < 0.001]).” The percentage of time that the glucose level was below 70 mg per deciliter did not differ significantly between the two groups, authors wrote (P = 0.57).
A glycated hemoglobin level of less than 7% is recommended by the American Diabetes Association according to authors. This target was met at 13 weeks in 30 of 62 closed-loop patients (48%) compared to 10 of 33 standard-care patients (30%).
In the closed-loop group, 71 adverse events were reported in 41 closed-loop patients (60%), while 14 adverse events in 11 standard-care patients (32%) were reported (P = 0.001). Three cases of severe hypoglycemia were reported: 2 in the closed-loop group and 1 in the standard-care group. There was 1 case of diabetic ketoacidosis related to infusion-set failure in the closed-loop group. There were 51 cases of hyperglycemia with or without ketosis (most of which were related to infusion-set failures) reported in the closed-loop group. Eight hyperglycemia cases, not related to the trial device, were reported in the standard-care group.
Overall, results demonstrated that the glucose level was in the target range was significantly longer (by approximately 3 hours per day) in closed-loop patients than those who used standard care, according to the study. Increased time in the target range was observed across various patient characteristics including age, race or ethnic group, parental education, family income, baseline glycated hemoglobin level, and the insulin-delivery method used before the trial.
Wadwa RP, Reed ZW, Buckingham BA, et al. Trial of hybrid closed-loop control in young children with type 1 diabetes. N Engl J Med. 2023;388(11):991-1001. doi:10.1056/NEJMoa2210834