Meta-analysis of overnight closed-loop randomized studies in children and adults with type 1 diabetes: the Cambridge cohort

Abstract

Aim: We reviewed the safety and efficacy of overnight closed-loop insulin delivery compared with conventional continuous subcutaneous insulin infusion (CSII) in two distinct age groups with type 1 diabetes mellitus (T1DM), young people aged 5 to 18 years and adults, combining data of previously published randomized studies.

Methods: We evaluated four randomized crossover studies in 17 children and adolescents [13.4 ± 3.6 years; mean ± standard deviation (SD)] and 24 adults (37.5 ± 9.1 years) on 45 closed-loop (intervention) and 45 CSII (control) visits. Each subject attended for two overnight study visits, using either closed-loop or conventional pump therapy, in random order. In each age group, studies were designed to mimic realistic likely scenarios. In the children and adolescent studies, closed loop was used following a standard evening meal and following 40 min of moderate-intensity exercise. In the adult studies, closed loop was commenced following a 60 g carbohydrate meal or a 100 g carbohydrate meal accompanied by alcohol. The primary outcome measure was time for which plasma glucose was within target range (3.91-8.0 mmol/liter).

Results: Overnight closed loop increased the time in target plasma glucose in both young (from 40% to 60%, p = .002) and adults (from 50% to 76%, p < .001) compared with conventional CSII. Combined analysis showed an increase from 43% to 71% with closed loop (p < .001). Additionally, closed loop reduced the time spent below 3.91 mmol/liter and above 8.0 mmol/liter, from 4.1% to 2.1% (p = .01) and 33% to 20% (p = .03), respectively. Glycemic variability, as measured by the SD of plasma glucose, was lower during closed loop compared with CSII (1.5 versus 2.1 mmol/liter, p = .007).

Conclusions: Overnight closed loop may improve glycemic control and reduce nocturnal hypoglycemia in both young people and adults with T1DM.

© 2011 Diabetes Technology Society.

Figures

Figure 1

Study design (left panels) and overnight plasma glucose (right panels) for (A) APCam01, (B) APCam03, (C) Angela01, and (D) Angela02. Plasma glucose is represented as median and interquartile range (error bars). CHO, carbohydrate. (Right panels of (A) and (B) are reprinted from Reference 18 with permission from Elsevier.)

Figure 2

Sample closed-loop night as seen on the computer interface during Angela01 study. Plot shows sensor glucose (solid red curve) and insulin infusion rate (blue curve). Plasma glucose (red dots) was added later during post hoc analysis. On this study visit at 19:00, the subject consumed a 60 g carbohydrate evening meal accompanied by a dual wave insulin bolus delivered as 2 U immediately and 2 U over 3 h. Closed-loop insulin delivery was operational from 19:00 to 08:00.

Figure 3

Comparison of plasma glucose in target range (3.91– 8.0 mmol/liter) for young, adults, and combined studies. Median with interquartile range shown. CL, closed loop.

Figure 4

Comparison of plasma glucose below 3.9 mmol/liter for young, adults, and combined studies. Median with interquartile range shown. CL, closed loop.

Figure 5

Comparison of plasma glucose above 8.0 mmol/liter for young, adults, and combined studies. Median with interquartile range shown. CL, closed loop.

Figure 6

Distribution of plasma glucose after midnight in young and adults during closed-loop (top panel) and during conventional pump (bottom panel) therapy. Vertical dashed lines denote the threshold of significant hypoglycemia (3.0 mmol/liter) and the target glucose range (3.91 to 8.0 mmol/liter). Values at the top represent the percentage of plasma glucose values within the respective glucose ranges.