Summary 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. Funding Juvenile Diabetes Research Foundation; European Foundation for Study of Diabetes; Medical Research Council Centre for Obesity and Related Metabolic Diseases; National Institute for Health Research Cambridge Biomedical Research Centre.
Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve ...glucose control while alleviating the risk of hypoglycaemia in adults with HbA1c below 7·5% (58 mmol/mol).
In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2–4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2–4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9–10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed.
Between March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6–13·4; p<0·0001) during closed-loop delivery compared with usual pump therapy (65·6% SD 8·1 when participants used usual pump therapy vs 76·2% 6·4 when they used closed-loop). Compared with usual pump therapy, closed-loop delivery also reduced the proportion of time spent in hypoglycaemia: the proportion of time with glucose concentration below 3·5 mmol/L was reduced by 65% (53–74, p<0·0001) and below 2·8 mmol/L by 76% (59–86, p<0·0001). No episodes of serious hypoglycaemia or other serious adverse events occurred.
Use of day-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies are warranted.
Swiss National Science Foundation (P1BEP3_165297), JDRF, UK National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z).
We assessed whether fully closed-loop insulin delivery (the so-called artificial pancreas) is safe and effective compared with standard subcutaneous insulin therapy in patients with type 2 diabetes ...in the general ward.
For this single-centre, open-label, parallel-group, randomised controlled trial, we enrolled patients aged 18 years or older with type 2 diabetes who were receiving insulin therapy. Patients were recruited from general wards at Addenbrooke’s Hospital, Cambridge, UK. Participants were randomly assigned (1:1) by a computer-generated minimisation method to receive closed-loop insulin delivery (using a model-predictive control algorithm to direct subcutaneous delivery of rapid-acting insulin analogue without meal-time insulin boluses) or conventional subcutaneous insulin delivery according to local clinical guidelines. The primary outcome was time spent in the target glucose concentration range of 5·6–10·0 mmol/L during the 72 h study period. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01774565.
Between Feb 20, 2015, and March 24, 2016, we enrolled 40 participants, of whom 20 were randomly assigned to the closed-loop intervention group and 20 to the control group. The proportion of time spent in the target glucose range was 59·8% (SD 18·7) in the closed-loop group and 38·1% (16·7) in the control group (difference 21·8% 95% CI 10·4–33·1; p=0·0004). No episodes of severe hypoglycaemia or hyperglycaemia with ketonaemia occurred in either group. One adverse event unrelated to study devices occurred during the study (gastrointestinal bleed).
Closed-loop insulin delivery without meal-time boluses is effective and safe in insulin-treated adults with type 2 diabetes in the general ward.
Diabetes UK; European Foundation for the Study of Diabetes; JDRF; National Institute for Health Research Cambridge Biomedical Research Centre; Wellcome Trust.
Closed-loop insulin delivery is a promising option to improve glycaemic control and reduce the risk of hypoglycaemia. We aimed to assess whether overnight home use of automated closed-loop insulin ...delivery would improve glucose control.
We did this open-label, multicentre, randomised controlled, crossover study between Dec 1, 2012, and Dec 23, 2014, recruiting patients from three centres in the UK. Patients aged 18 years or older with type 1 diabetes were randomly assigned to receive 4 weeks of overnight closed-loop insulin delivery (using a model-predictive control algorithm to direct insulin delivery), then 4 weeks of insulin pump therapy (in which participants used real-time display of continuous glucose monitoring independent of their pumps as control), or vice versa. Allocation to initial treatment group was by computer-generated permuted block randomisation. Each treatment period was separated by a 3–4 week washout period. The primary outcome was time spent in the target glucose range of 3·9–8·0 mmol/L between 0000 h and 0700 h. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01440140.
We randomly assigned 25 participants to initial treatment in either the closed-loop group or the control group, patients were later crossed over into the other group; one patient from the closed-loop group withdrew consent after randomisation, and data for 24 patients were analysed. Closed loop was used over a median of 8·3 h (IQR 6·0–9·6) on 555 (86%) of 644 nights. The proportion of time when overnight glucose was in target range was significantly higher during the closed-loop period compared to during the control period (mean difference between groups 13·5%, 95% CI 7·3–19·7; p=0·0002). We noted no severe hypoglycaemic episodes during the control period compared with two episodes during the closed-loop period; these episodes were not related to closed-loop algorithm instructions.
Unsupervised overnight closed-loop insulin delivery at home is feasible and could improve glucose control in adults with type 1 diabetes.
Diabetes UK.
Objective To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (FiO2 ) in maintaining arterial oxygen saturation (SpO2 ) within a higher (91%-95%) and a ...lower (89%-93%) target range in preterm infants. Study design Eighty preterm infants (gestational age median: 26 weeks, age median 18 days) on noninvasive (n = 50) and invasive (n = 30) respiratory support with supplemental oxygen, were first randomized to one of the SpO2 target ranges and then treated with automated FiO2 (A-FiO2 ) and manual FiO2 (M-FiO2 ) oxygen control for 24 hours each, in random sequence. Results The percent time within the target range was higher during A-FiO2 compared with M-FiO2 control. This effect was more pronounced in the lower SpO2 target range (62 ± 17% vs 54 ± 16%, P < .001) than in the higher SpO2 target range (62 ± 17% vs 58 ± 15%, P < .001). The percent time spent below the target or in hypoxemia (SpO2 <80%) was consistently reduced during A-FiO2 , independent of the target range. The time spent above the target range or at extreme hyperoxemia (SpO2 >98%) was only reduced during A-FiO2 when targeting the lower SpO2 range (89%-93%). These outcomes did not differ between infants on noninvasive and invasive respiratory support. Manual adjustments were significantly reduced during A-FiO2 control. Conclusions A-FiO2 control improved SpO2 targeting across different SpO2 ranges and reduced hypoxemia in preterm infants on noninvasive and invasive respiratory support. Trial registration ISRCTN 56626482.
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