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Discover the most talked about and latest scientific content & concepts.

Concept: Insulin pump

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The artificial pancreas (closed-loop system) addresses the unmet clinical need for improved glucose control whilst reducing the burden of diabetes self-care in type 1 diabetes. Glucose-responsive insulin delivery above and below a preset insulin amount informed by sensor glucose readings differentiates closed-loop systems from conventional, threshold-suspend and predictive-suspend insulin pump therapy. Insulin requirements in type 1 diabetes can vary between one-third-threefold on a daily basis. Closed-loop systems accommodate these variations and mitigate the risk of hypoglycaemia associated with tight glucose control. In this review we focus on the progress being made in the development and evaluation of closed-loop systems in outpatient settings. Randomised transitional studies have shown feasibility and efficacy of closed-loop systems under supervision or remote monitoring. Closed-loop application during free-living, unsupervised conditions by children, adolescents and adults compared with sensor-augmented pumps have shown improved glucose outcomes, reduced hypoglycaemia and positive user acceptance. Innovative approaches to enhance closed-loop performance are discussed and we also present the outlook and strategies used to ease clinical adoption of closed-loop systems.

Concepts: Closed loop, Control theory, Diabetes, Glucagon, Diabetes mellitus type 1, Insulin pump, Diabetes mellitus, Insulin

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To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes.

Concepts: Term, Diabetes mellitus type 2, Diabetes, Subcutaneous injection, Diabetes mellitus, Diabetes mellitus type 1, Insulin pump, Insulin

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Objective To compare the effectiveness of insulin pumps with multiple daily injections for adults with type 1 diabetes, with both groups receiving equivalent training in flexible insulin treatment.Design Pragmatic, multicentre, open label, parallel group, cluster randomised controlled trial (Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial).Setting Eight secondary care centres in England and Scotland.Participants Adults with type 1 diabetes who were willing to undertake intensive insulin treatment, with no preference for pumps or multiple daily injections. Participants were allocated a place on established group training courses that taught flexible intensive insulin treatment (“dose adjustment for normal eating,” DAFNE). The course groups (the clusters) were then randomly allocated in pairs to either pump or multiple daily injections.Interventions Participants attended training in flexible insulin treatment (using insulin analogues) structured around the use of pump or injections, followed for two years.Main outcome measures The primary outcomes were a change in glycated haemoglobin (HbA1c) values (%) at two years in participants with baseline HbA1c value of ≥7.5% (58 mmol/mol), and the proportion of participants achieving an HbA1c value of <7.5%. Secondary outcomes included body weight, insulin dose, and episodes of moderate and severe hypoglycaemia. Ancillary outcomes included quality of life and treatment satisfaction.Results 317 participants (46 courses) were randomised (156 pump and 161 injections). 267 attended courses and 260 were included in the intention to treat analysis, of which 235 (119 pump and 116 injection) had baseline HbA1c values of ≥7.5%. Glycaemic control and rates of severe hypoglycaemia improved in both groups. The mean change in HbA1c at two years was -0.85% with pump treatment and -0.42% with multiple daily injections. Adjusting for course, centre, age, sex, and accounting for missing values, the difference was -0.24% (-2.7 mmol/mol) in favour of pump users (95% confidence interval -0.53 to 0.05, P=0.10). Most psychosocial measures showed no difference, but pump users showed greater improvement in treatment satisfaction and some quality of life domains (dietary freedom and daily hassle) at 12 and 24 months.Conclusions Both groups showed clinically relevant and long lasting decreases in HbA1c, rates of severe hypoglycaemia, and improved psychological measures, although few participants achieved glucose levels currently recommended by national and international guidelines. Adding pump treatment to structured training in flexible intensive insulin treatment did not substantially enhance educational benefits on glycaemic control, hypoglycaemia, or psychosocial outcomes in adults with type 1 diabetes. These results do not support a policy of providing insulin pumps to adults with poor glycaemic control until the effects of training on participants' level of engagement in intensive self management have been determined.Trial registration Current Controlled Trials ISRCTN61215213.

Concepts: Insulin pump, Clinical trial, Hypoglycemia, Diabetes mellitus type 1, Diabetes, Diabetes mellitus, Randomized controlled trial, Insulin

28

Pursuit of a closed-loop artificial pancreas that automatically controls the blood glucose of individuals with type 1 diabetes has intensified during the past six years. Here we discuss the recent progress and challenges in the major steps towards a closed-loop system. Continuous insulin infusion pumps have been widely available for over two decades, but “smart pump” technology has made the devices easier to use and more powerful. Continuous glucose monitoring (CGM) technology has improved and the devices are more widely available. A number of approaches are currently under study for fully closed-loop systems; most manipulate only insulin, while others manipulate insulin and glucagon. Algorithms include on-off (for prevention of overnight hypoglycemia), proportional-integral-derivative (PID), model predictive control (MPC) and fuzzy logic based learning control. Meals cause a major “disturbance” to blood glucose, and we discuss techniques that our group has developed to predict when a meal is likely to be consumed and its effect. We further examine both physiology and device-related challenges, including insulin infusion set failure and sensor signal attenuation. Finally, we discuss the next steps required to make a closed-loop artificial pancreas a commercial reality.

Concepts: Blood glucose monitoring, Glucagon, Diabetes, Fuzzy logic, Insulin pump, Diabetes mellitus, Insulin, Control theory

27

To review the available evidence regarding dosing conversion between glargine and detemir in an effort to assist clinicians in performing dosing conversion.

Concepts: Insulin pump, Insulin therapies

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Continuous glucose monitoring (CGM) systems have been available for more than 15 years by now. However, market uptake is relatively low in most countries; in other words, relatively few patients with diabetes use CGM systems regularly. One major reason for the reluctance of patients to use CGM systems is the costs associated (i.e., in most countries no reimbursement is provided by the health insurance companies). In case reimbursement is in place, like in the United States, only certain patient groups get reimbursement that fulfills strict indications. This situation is somewhat surprising in view of the mounting evidence for benefits of CGM usage from clinical trials: most meta-analyses of these trials consistently show a clinically relevant improvement of glucose control associated with a reduction in hypoglycemic events. More recent trials with CGM systems with an improved CGM technology showed even more impressive benefits, especially if CGM systems are used in different combinations with an insulin pump (e.g., with automated bolus calculators and low glucose suspend features). Nevertheless, sufficient evidence is not available for all patient groups, and more data on cost-efficacy are needed. In addition, good data from real-world studies/registers documenting the benefits of CGM usage under daily life conditions would be of help to convince healthcare systems to cover the costs of CGM systems. In view of the ongoing improvements in established needle-type CGM systems, the fact that new CGM technology will come to the market soon (e.g., implantable sensors), that CGM-like systems are quite successfully at least in certain markets (like the flash glucose monitoring systems), and that the first artificial pancreas systems will come to the market in the next few years, there is a need to make sure that this major improvement in diabetes therapy becomes more widely available for patients with diabetes, for which better reimbursement is essential.

Concepts: Diabetes, Insulin pump, Diabetes mellitus, Hypoglycemia, Improve, Better, Blood glucose monitoring, Insulin

21

Continuous glucose monitoring (CGM) provides information unattainable by intermittent capillary blood glucose, including instantaneous real-time display of glucose level and rate of change of glucose, alerts and alarms for actual or impending hypo- and hyperglycemia, “24/7” coverage, and the ability to characterize glycemic variability. Progressively more accurate and precise, reasonably unobtrusive, small, comfortable, user-friendly devices connect to the Internet to share information and are sine qua non for a closed-loop artificial pancreas. CGM can inform, educate, motivate, and alert people with diabetes. CGM is medically indicated for patients with frequent, severe, or nocturnal hypoglycemia, especially in the presence of hypoglycemia unawareness. Surprisingly, despite tremendous advances, utilization of CGM has remained fairly limited to date. Barriers to use have included the following: (1) lack of Food and Drug Administration approval, to date, for insulin dosing (“nonadjuvant use”) in the United States and for use in hospital and intensive care unit settings; (2) cost and variable reimbursement; (3) need for recalibrations; (4) periodic replacement of sensors; (5) day-to-day variability in glycemic patterns, which can limit the predictability of findings based on retrospective, masked “professional” use; (6) time, implicit costs, and inconvenience for uploading of data for retrospective analysis; (7) lack of fair and reasonable reimbursement for physician time; (8) inexperience and lack of training of physicians and other healthcare professionals regarding interpretation of CGM results; (9) lack of standardization of software methods for analysis of CGM data; and (10) need for professional medical organizations to develop and disseminate additional clinical practice guidelines regarding the role of CGM. Ongoing advances in technology and clinical research have addressed several of these barriers. Use of CGM in conjunction with an insulin pump with automated suspension of insulin infusion in response to actual observed or predicted hypoglycemia, as well as progressive refinement of closed-loop systems, is expected to dramatically enhance the clinical utility and utilization of CGM.

Concepts: Clinical trial, Medicine, Diabetes, Carbohydrate, Insulin pump, Insulin, Blood glucose monitoring, Diabetes mellitus

21

To compare the efficacy and safety of new insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs).

Concepts: Obesity, Insulin glargine, Insulin therapies, Anti-diabetic drugs, Insulin pump, Insulin, Diabetes mellitus, Diabetes mellitus type 2

16

This study was performed to understand and to compare differences in utilization of continuous glucose monitoring (CGM) and the rate of change (ROC) arrow to adjust insulin therapy among individuals with type 1 diabetes (T1D), comparing those treated with multiple daily insulin injections (MDI) with those treated with continuous subcutaneous insulin infusion (CSII).

Concepts: Insulin pump, Diabetes, Blood glucose monitoring, Insulin therapy, Diabetes mellitus type 2, Diabetes mellitus, Diabetes mellitus type 1, Insulin

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Background: The automatic Threshold Suspend (TS) feature of the MiniMed 530G system (Medtronic MiniMed, Inc., Northridge, CA), when enabled, suspends insulin delivery for up to 2 h when the sensor glucose (SG) value reaches a preset threshold. Materials and Methods: SG data from 20,973 patients who enabled the TS feature at their discretion and uploaded pump and sensor data to CareLink(®) (Medtronic MiniMed, Inc.) from October 15, 2013 to July 21, 2014 were analyzed. Comparisons between 758,382 patient-days wherein the TS feature was enabled at any time and 166,791 patient-days in which it was not enabled were made. Further comparisons were made between data collected during daytime (8:00 a.m. to 10:00 p.m.) and nighttime (10:00 p.m. to 8:00 a.m.) hours. Data from subsets of patients who enabled the TS feature all of the time (n=14,673) versus those who never enabled the TS feature (n=2,249) were also compared. Recovery from hypoglycemia during and after 2-h pump suspension events was also assessed. Results: The TS feature was enabled on 82% of patient-days. Patient-days in which the TS feature was enabled, compared with patient-days in which it was not, had 69% fewer SG values ≤50 mg/dL (0.64% vs. 2.09%, respectively; P<0.001). The reduction in hypoglycemia seen on TS-enabled days was more pronounced during nighttime than during daytime hours. SG data from full-time users of the TS feature reflected a 62% reduction in values ≤50 mg/dL and a 5.6% reduction in values ≥300 mg/dL compared with data from nonusers (P<0.001 for each). The median SG value at the start of 2-h suspensions was 60 (interquartile range [IQR], 57-66) mg/dL, immediately after was 87 (IQR, 63-123) mg/dL, and 4 h later was 164 (IQR, 117-220) mg/dL. Conclusions: The TS feature, when enabled consistently, reduced hypoglycemic exposure, and for those who had it enabled 100% of the time, hyperglycemia was also reduced.

Concepts: Value, Medtronic, Median, Insulin, Insulin pump, Hypoglycemia, Glucose meter, Interquartile range