Closed-Loop Insulin Pump Therapy in Young Type 1 Diabetic Children

Abstract

Source: Ware J, Allen JM, Boughton CK, et al. Randomized trial of closed-loop control in very young children with type 1 diabetes. N Engl J Med. 2022;386:209-219; doi: 10.1056/NEJMoa2111673Investigators from multiple institutions conducted a crossover randomized trial to compare the effectiveness and safety of a closed-loop system (ie, artificial pancreas) to sensor-augmented insulin pump therapy in young children with type 1 diabetes. Participants were children 1-7 years old with a diagnosis of type 1 diabetes for at least 6 months, recruited from diabetes centers in 4 European countries. The closed-loop system consisted of a continuous glucose sensor and insulin pump connected to a smartphone app. The app included an algorithm that automatically adjusted insulin delivery based on real-time sensor glucose readings. With the sensor-augmented pump, insulin therapy was stopped if an algorithm predicted that sensor glucose levels were likely to drop below a specified threshold. Study children were randomized to receive 16 weeks of treatment with the closed loop system, followed by 16 weeks using the augmented-sensor pump, or vice versa. The primary outcome was percentage of time spent in the target glucose range (70 to 170 mg/dL) during each treatment period. Secondary outcomes included percentage of time spent in a hyperglycemic range (>180 mg/dL) and hypoglycemic range (<70 mg/dL) and mean glucose levels. These outcomes were based on readings from the glucose sensors. Glycated hemoglobin levels were measured at baseline and at the end of each treatment period. Differences in outcomes between the closed-loop and sensor-augmented pump treatment period were assessed with repeated-measures linear regression models. Data on adverse events also were collected.Data were analyzed on 74 children with a mean age of 5.6 ±1.6 years. The mean glycated hemoglobin level at baseline was 7.3 ±0.7%. The mean time spent in the target glucose range were 71.6 ±5.9% during the closed-loop period and 62.9 ±9.0% in the sensor-augmented pump period (adjusted difference, 8.7 percentage points; 95% CI, 7.4, 9.9; P <0.001). The median time spent at glucose level >180 mg/dL was significantly less during the closed-loop period than during the control period (22.9% vs 31.7%; adjusted difference, -8.5 percentage points; 95% CI, -.9.9, -7.1; P <0.001); mean sensor glucose levels (145 ±11.8 mg/dL and 158.1 ±18.5 mg/dL, respectively; P <0.001) and mean glycated hemoglobin levels (6.6 ±0.6% and 7.0 ±0.7%) were significantly lower during the closed-loop period than during treatment with the segmented-sensor pump. There was no difference between treatment periods for percentage of time with glucose <70 mg/dL (P = 0.74). One participant had a serious adverse event (severe hypoglycemia) during their closed-loop treatment period.The authors conclude that a closed-loop system improved glycemic control in young children with type 1 diabetes.Dr Fechner has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Type 1 diabetes is very difficult to manage in the young child. The therapeutic window for insulin is very narrow, with too much insulin resulting in hypoglycemia and too little insulin resulting in hyperglycemia. The last 5 years have seen tremendous advances in the technology available to children with type 1 diabetes. A 2019 study comparing the insulin pump to multiple daily injections showed that the insulin pump was superior to multiple daily injections. (See AAP Grand Rounds. 2019;42[1]:4.) Continuous glucose monitoring has decreased parental anxiety regarding risk of hypoglycemia and diabetic ketoacidosis;1 however, parents still are responsible for making insulin dose adjustments, and glycemic control overall is not improved.2 The results of a 2020 study of 6- to 13-year-olds with type 1 diabetes demonstrated that glucose levels were in the target range for a longer period of time in those randomized to a closed-loop system than those using a sensor-augmented pump. (See AAP Grand Rounds. 2020;44[6]:69.)3 The current researchers compared a hybrid closed-loop insulin delivery system to sensor-augmented pump therapy in younger children with type I diabetes.The strengths of the current study are the randomized, crossover design using the same algorithm with the closed-loop functionality either abled or disabled; each therapy was 16 weeks, which allowed a meaningful glycated hemoglobin to be obtained. There were no restrictions on previous episodes of hypoglycemia and diabetic ketoacidosis, and the study included a very young children with diabetes, who are more vulnerable to hypo- and hyperglycemia. Weaknesses of this study include underrepresentation of ethnic minorities and a patient population not representative of the typical type 1 diabetes population, as the average glycated hemoglobin level was 7.3% at baseline.4 Decreased patient compliance outside of the confines of a study may be reflected in poorer glucose control regardless of the insulin delivery system used.Hybrid closed-loop insulin therapy in young children with type 1 diabetes has the potential to significantly improve long-term outcomes through improved glycemic control.