Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial.

BACKGROUND: Closed-loop systems link continuous glucose measurements to insulin delivery. We aimed to establish whether closed-loop insulin delivery could control overnight blood glucose in young people. METHODS: We undertook three randomised crossover studies in 19 patients aged 5-18 years with type 1 diabetes of duration 6.4 years (SD 4.0). We compared standard continuous subcutaneous insulin infusion and closed-loop delivery (n=13; APCam01); closed-loop delivery after rapidly and slowly absorbed meals (n=7; APCam02); and closed-loop delivery and standard treatment after exercise (n=10; APCam03). Allocation was by computer-generated random code. Participants were masked to plasma and sensor glucose. In APCam01, investigators were masked to plasma glucose. During closed-loop nights, glucose measurements were fed every 15 min into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. During control nights, patients' standard pump settings were applied. Primary outcomes were time for which plasma glucose concentration was 3.91-8.00 mmol/L or 3.90 mmol/L or lower. Analysis was per protocol. This trial is registered, number ISRCTN18155883. FINDINGS: 17 patients were studied for 33 closed-loop and 21 continuous infusion nights. Primary outcomes did not differ significantly between treatment groups in APCam01 (12 analysed; target range, median 52% [IQR 43-83] closed loop vs 39% [15-51] standard treatment, p=0.06;

Automated overnight closed-loop glucose control in young children with type 1 diabetes.

BACKGROUND: We evaluated the effectiveness of automated overnight closed-loop (AOCL) insulin delivery and the influence of timing of initiation on glucose control overnight in young children with type 1 diabetes (T1D). METHODS: Eight children with T1D (four boys, four girls) (mean ± SD: 9.4 ± 2.7 years old; body mass index, 18.3 ± 2.3 kg/m(2); duration of diabetes, 3.9 ± 2.5 years; total daily insulin dose, 0.7 ± 0.1 U/kg/day; glycosylated hemoglobin, 7.9 ± 0.9%) were studied in a clinical research facility on two separate occasions. Subjects had a meal at 18:00 (77 ± 8 g of carbohydrate [CHO]) and snack at 21:00 (21 ± 6 g of CHO), both accompanied by a prandial insulin bolus. In random order, AOCL was started at 18:00 or 21:00 h and ran until 08:00 h the next day. Subcutaneous continuous glucose monitoring data were fed automatically into the model predictive control algorithm. Calculated subcutaneous insulin infusion rates were sent wirelessly to an insulin pump. Plasma glucose was measured to assess closed-loop performance. RESULTS: No rescue CHOs were administered. Time spent with plasma glucose in the target range from 3.9 to 8.0 mmol/L was 50.7% (29.0%, 72.2%), and it did not differ on the two occasions: median (interquartile range), 42% (18%, 64%) versus 58% (32%, 79%) (P = 0.161). Time when plasma glucose was above 8.0 mmol/L (42% [25%, 82%] vs. 29% [14%, 64%], P = 0.093), time below 3.9 mmol/L (0% [0%, 11%] vs. 8% [0%, 17%], P = 0.500), low blood glucose index (0.1 [0.0, 2.5] vs. 1.7 [0.4, 3.3], P = 0.380), plasma glucose at the start of AOCL (12.5 ± 2.7 vs. 11.6 ± 4.2 mmol/L, P = 0.562), and mean overnight plasma glucose (8.3 ± 2.1 vs. 7.5 ± 2.2 mmol/L, P = 0.246) were also similar. CONCLUSIONS: AOCL is feasible in young children with T1D. Comparable results were obtained when closed-loop was initiated at 18:00 or 21:00 h.

Effect of delay on measurement of blood glucose levels in young subjects with type 1 diabetes.

We investigated the effect of a 3-h time-lag between blood sampling and glucose measurement in type 1 diabetes. Blood glucose decreased by 0.47 mmol/L despite samples being collected in fluoride tubes and placed on ice. The extent of reduction differs among subjects, prevailing blood glucose and time-of-day of sample withdrawal.