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

被引:296
作者
Hovorka, Roman [1 ,2 ]
Allen, Janet M. [1 ,2 ]
Elleri, Daniela [1 ,2 ]
Chassin, Ludovic J. [1 ,2 ]
Harris, Julie [2 ]
Xing, Dongyuan [3 ]
Kollman, Craig [3 ]
Hovorka, Tomas [1 ]
Larsen, Anne Mette F. [1 ,2 ]
Nodale, Marianna [1 ]
De Palma, Alessandro [1 ]
Wilinska, Malgorzata E. [1 ,2 ]
Acerini, Carlo L. [1 ,2 ]
Dunger, David B. [1 ,2 ]
机构
[1] Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England
[2] Univ Cambridge, Inst Metab Sci, Cambridge CB2 0QQ, England
[3] Jaeb Ctr Hlth Res, Tampa, FL USA
基金
英国医学研究理事会; 英国惠康基金;
关键词
SEVERE HYPOGLYCEMIA; GLUCOSE; ROADMAP;
D O I
10.1016/S0140-6736(09)61998-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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; <= 3.90 mmol/L, 1% [0-7] vs 2% [0-41], p=0.13), APCam02 (six analysed; target range, rapidly 53% [48-57] vs slowly absorbed meal 55% [37-64], p=0.97; <= 3.90 mmol/L, 0% [0-4] vs 0% [0-0], p=0.16]), and APCam03 (nine analysed; target range 78% [60-92] closed loop vs 43% [25-65] control, p=0.0245, not significant at corrected level; <= 3.90 mmol/L, 10% [2-15] vs 6% [0-44], p=0.27). A secondary analysis of pooled data documented increased time in the target range (60% [51-88] vs 40% [18-61]; p=0.0022) and reduced time for which glucose concentrations were 3.90 mmol/L or lower (2.1% (0.0-10.0) vs 4.1% (0.0-42.0); p=0.0304). No events with plasma glucose concentration lower than 3.0 mmol/L were recorded during closed-loop delivery compared with nine events during standard treatment. Interpretation Closed-loop systems could reduce risk of nocturnal hypoglycaemia in children and adolescents with type 1 diabetes.
引用
收藏
页码:743 / 751
页数:9
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