IntroductionMedical devices, including high-risk medical devices, have greatly contributed to recent improvements in the management of diabetes. However, the clinical evidence that is submitted for ...regulatory approval is not transparent, and thus a comprehensive summary of the evidence for high-risk devices approved for managing diabetes in Europe is lacking. In the framework of the Coordinating Research and Evidence for Medical Devices group, we will, therefore, perform a systematic review and meta-analysis, which will evaluate the efficacy, safety and usability of high-risk medical devices for the management of diabetes.Method and analysisThis study has been reported according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search Embase (Elsevier), Medline All (Ovid), Cochrane Library (Wiley), Science Citation Index Expanded and Emerging Sources Citation Index (Web of Science) to identify interventional and observational studies that evaluate the efficacy and/or safety and/or usability of high-risk medical devices for the management of diabetes. No language or publication dates’ limits will be applied. Animal studies will be excluded. In accordance with the Medical Device Regulation in European Union, high-risk medical devices are those in classes IIb and III. The following medical devices for diabetes management are considered as having a high risk: implantable continuous glucose monitoring systems, implantable pumps and automated insulin delivery devices. Selection of studies, data extraction and quality of evidence assessment will be performed independently by two researchers. Sensitivity analysis will be performed to identify and explain potential heterogeneity.Ethics and disseminationNo ethical approval is needed for this systematic review, as it is based in already published data. Our findings will be published in a peer-reviewed journal.PROSPERO registration numberCRD42022366871.
Closed-loop (CL) systems modulate insulin delivery according to glucose levels without nurse input. In a prospective randomized controlled trial, we evaluated the feasibility of an automated ...closed-loop approach based on subcutaneous glucose measurements in comparison with a local sliding-scale insulin-therapy protocol.
Twenty-four critically ill adults (predominantly trauma and neuroscience patients) with hyperglycemia (glucose, ≥10 mM) or already receiving insulin therapy, were randomized to receive either fully automated closed-loop therapy (model predictive control algorithm directing insulin and 20% dextrose infusion based on FreeStyle Navigator continuous subcutaneous glucose values, n = 12) or a local protocol (n = 12) with intravenous sliding-scale insulin, over a 48-hour period. The primary end point was percentage of time when arterial blood glucose was between 6.0 and 8.0 mM.
The time when glucose was in the target range was significantly increased during closed-loop therapy (54.3% (44.1 to 72.8) versus 18.5% (0.1 to 39.9), P = 0.001; median (interquartile range)), and so was time in wider targets, 5.6 to 10.0 mM and 4.0 to 10.0 mM (P ≤ 0.002), reflecting a reduced glucose exposure >8 and >10 mM (P ≤ 0.002). Mean glucose was significantly lower during CL (7.8 (7.4 to 8.2) versus 9.1 (8.3 to 13.0 mM; P = 0.001) without hypoglycemia (<4 mM) during either therapy.
Fully automated closed-loop control based on subcutaneous glucose measurements is feasible and may provide efficacious and hypoglycemia-free glucose control in critically ill adults.
ClinicalTrials.gov Identifier, NCT01440842.
Since the discovery of insulin 100 years ago, we have seen considerable advances across diabetes therapies. The more recent advent of glucose-responsive automated insulin delivery has started to ...revolutionise the management of type 1 diabetes in children and adults. Evolution of closed-loop insulin delivery from research to clinical practice has been rapid, and multiple systems are now commercially available. In this review, we summarise key evidence on currently available closed-loop systems and those in development. We comment on dual-hormone and do-it-yourself systems, as well as reviewing clinical evidence in special populations such as very young children, older adults and in pregnancy. We identify future directions for research and barriers to closed-loop adoption, including how these might be addressed to ensure equitable access to this novel therapy.
•Type 1 diabetes is a lifelong condition with high management burden.•Glucose-responsive automated insulin delivery improves glycaemic outcomes and quality of life.•Multiple closed-loop systems are commercially available, offering increased choice for users.•Working towards a fully closed-loop system and addressing barriers to adoption should be the focus of future research.
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.
Studies have shown that overnight closed-loop insulin delivery can improve glucose control and reduce the risk of hypoglycemia and hence may improve metabolic outcomes and reduce burden for children ...with type 1 diabetes and their families. However, research so far has not reported insulin levels while comparing closed-loop to open-loop insulin delivery in children. Therefore, in this study we obtained glucose levels as well as plasma insulin levels in children with type 1 diabetes to evaluate the efficacy of a model-based closed-loop algorithm compared to an open-loop administration.
Fifteen children with type 1 diabetes, 6-12 years, participated in this open-label single center study. We used a randomized cross over design in which we compared overnight closed-loop insulin delivery with sensor augmented pump therapy for two nights in both the hospital and at home (i.e., 1 night in-patient stay and at home per treatment condition). Only during the in-patient stay, hourly plasma insulin and blood glucose levels were assessed and are reported in this paper.
Results of paired sample t-tests revealed that although plasma insulin levels were significantly lower during the closed-loop than in the open-loop (Mean difference 36.51 pmol/l; t(13) = 2.13, p = .03, effect size d = 0.57), blood glucose levels did not vary between conditions (mean difference 0.76 mmol/l; t(13) = 1.24, p = .12, d = 0.37). The administered dose of insulin was significantly lower during the closed-loop compared with the open-loop (mean difference 0.10 UI; t(12) = 2.45, p = .02, d = 0.68).
Lower insulin doses were delivered in the closed-loop, resulting in lower plasma insulin levels, whereby glucose levels were not affected negatively. This suggests that the closed-loop administration is better targeted and hence could be more effective.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Over the last five years, closed-loop insulin delivery systems have transitioned from research-only to real-life use. A number of systems have been commercialized and are increasingly used in ...clinical practice. Given the rapidity of new developments in the field, understanding the capabilities and key similarities and differences of current systems can be challenging. This review aims to provide an update on the state of the field of closed-loop insulin delivery systems, including emerging technologies.
We summarize key clinical safety and efficacy evidence of commercial and emerging insulin-only hybrid closed-loop systems for type 1 diabetes. A literature search was conducted and clinical trials using closed-loop systems during free-living conditions were identified to report on safety and efficacy data. We comment on emerging technologies and adjuncts for closed-loop systems, as well as non-technological priorities in closed-loop insulin delivery.
Commercial hybrid closed-loop insulin delivery systems are efficacious, consistently improving glycemic control when compared to standard therapy. Challenges remain in widespread adoption due to clinical inertia and the lack of resources to embrace technological developments by health care professionals.
Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including ...continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes.
A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events.
This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy.
ISRCTN 56898625 Registration Date: 10 April, 2018.
New closed-loop insulin systems Boughton, Charlotte K.; Hovorka, Roman
Diabetologia,
05/2021, Letnik:
64, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Advances in diabetes technologies have enabled the development of automated closed-loop insulin delivery systems. Several hybrid closed-loop systems have been commercialised, reflecting rapid ...transition of this evolving technology from research into clinical practice, where it is gradually transforming the management of type 1 diabetes in children and adults. In this review we consider the supporting evidence in terms of glucose control and quality of life for presently available closed-loop systems and those in development, including dual-hormone closed-loop systems. We also comment on alternative ‘do-it-yourself’ closed-loop systems. We remark on issues associated with clinical adoption of these approaches, including training provision, and consider limitations of presently available closed-loop systems and areas for future enhancements to further improve outcomes and reduce the burden of diabetes management.
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