Accuracy assessment of bolus and basal rate delivery of different insulin pump systems used in insulin pump therapy of children and adolescents.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) is commonly used in patients with diabetes. Accurate and reliable delivery by insulin pumps is essential for a safe and effective therapy, particularly when using small doses. In this study, accuracy of bolus and basal rate delivery of various available insulin pumps was evaluated. METHODS: In total, 13 insulin pump systems were tested: eight durable pumps with different infusion sets and one patch pump. Based on IEC 60601-2-24, insulin delivery was measured by recording weight gain of a beaker into which insulin was infused by the pumps. Bolus accuracy was determined by individually weighing 25 consecutive 0.1 or 1.0 U boluses and basal rate accuracy was determined during basal rate delivery of 0.1 or 1.0 U/h for 72 hours. For analyses, basal rate delivery was divided into 1-hour windows and deviation from target was calculated. RESULTS: Regarding different systems, average 0.1 U bolus delivery was -2% to +9% of the intended volume with 53% to 96% of boluses within ±15% of target. During 0.1 U/h basal rate delivery, most pumps showed an initial over-delivery for the first few hours. Three systems reached a total basal rate error <5%; others showed up to +24%. In general, delivery was more accurate when using larger doses. CONCLUSIONS: Considerable differences in insulin delivery accuracy were observed between the tested pumps. In general, when using very low doses, accuracy of insulin delivery is limited in most insulin pumps. This should be considered for CSII therapy in children.

A Type 1 diabetes technology pathway: consensus statement for the use of technology in Type 1 diabetes.

In both adults and children with diabetes, technologies such as continuous subcutaneous insulin infusion using insulin pumps and continuous glucose monitoring can help improve diabetes control, reduce hypoglycaemia and improve quality of life. Access to these technologies in the UK is very variable. Some technologies are recommended by the National Institute for Health and Care Excellence, while others have not been appraised, and new technologies are emerging all the time. Additionally, different guidelines for adults and children further complicate access to diabetes technology in the transition from paediatric to adult care. Against this background, Diabetes UK and NHS England have brought together a multidisciplinary group of experts, including clinicians and people with diabetes, to develop this consensus guideline, combining the different technologies into a common pathway to aid clinical and policy decision-making. We created a pathway that supports the incremental addition of technology as monotherapy and then dual therapy in the same way that we incrementally add in therapeutic agents to support people with Type 2 diabetes to achieve their personalized glycaemic targets. The pathway emphasizes the importance of structured education, specialist support and appropriate access to psychological therapies, as essential pillars for optimized use of diabetes-related technology, and recommends the re-evaluation of its use when the individual is unable either to use the technology appropriately or to achieve the intended outcomes. This pathway is endorsed by UK-wide clinical and patient associations and we recommend that providers and commissioners use it to ensure the right individual with diabetes has access to the right technology in a timely way to help achieve better outcomes.

Is an artificial pancreas (closed-loop system) for Type 1 diabetes effective?

The artificial pancreas is now a viable treatment option for people with Type 1 diabetes and has demonstrated improved glycaemic outcomes while also reducing the onus of self-management of Type 1 diabetes. Closed-loop glucose-responsive insulin delivery guided by real-time sensor glucose readings can accommodate highly variable day-to-day insulin requirements and reduce the hypoglycaemia risk observed with tight glycaemic control in Type 1 diabetes. In 2011, the James Lind Alliance research priorities for Type 1 diabetes were produced and priority 3 was to establish whether an artificial pancreas (closed-loop system) for Type 1 diabetes is effective. This review focuses on the progress that has been made in the evolution of closed-loop systems as an effective treatment option for Type 1 diabetes. Development of closed-loop systems has advanced from feasibility evaluations in highly supervised settings over short periods, to clinical studies in free-living, unsupervised conditions lasting several months. The approval in the USA of the first hybrid closed-loop system (MiniMed® 670G pump, Medtronic, Northridge, CA, USA) in 2016 for use in Type 1 diabetes reflects these advancements. We discuss the evidence from clinical studies that closed-loop systems are effective with improved glycaemic outcomes, reduced hypoglycaemia and had positive end-user acceptance in children, adolescents, adults and pregnant women with Type 1 diabetes. We also present the outlook for future closed-loop systems in the treatment of Type 1 diabetes and identify the challenges facing the wide-spread clinical adoption of this technology.

Optimal predictive low glucose management settings during physical exercise in adolescents with type 1 diabetes.

OBJECTIVES: To assess the optimal setting of the predictive low glucose management (PLGM) algorithm for preventing exercise-induced hypoglycemia in adolescents with type 1 diabetes. METHODS: Thirty-four adolescents, 15 to 20 years, wearing PLGM system, were followed during 3 days exercise during a diabetes camp. PLGM threshold was set at 70 mg/dL between 8 am and 10 pm and 90 mg/dL during 10 pm and 8 am Adolescents were divided into group A and B, with PLGM threshold at 90 and 70 mg/dL, respectively, during exercise. Time spent in hypoglycemia and AUC for time slots 8 am to 1 pm, 1 to 4 pm, 4 to 11 pm, 11 pm to 3 am, 3 to 8 am, in 3 days were compared between groups by Wilcoxon rank sum test. RESULTS: We analyzed 31 patients (median age 15.0 years, 58.1% males, median diabetes duration 7.0 years, hemoglobin A1c [HbA1c] 7.1%). No significant difference has been observed in time spent in hypoglycemia between groups using threshold 70 or 90. Time spent in target was similar in both groups, as well as time spent in hypo or hyperglycemia. The trends of blood glucose over the 3 days in the 2 groups over-lapped without significant differences. CONCLUSIONS: A PLGM threshold of 90 mg/dL during the night was associated with reduced time in hypoglycemia in adolescents doing frequent physical exercise, while maintaining 65.1% time in range during the day. However, a threshold of 70 mg/dL seems to be safe in the duration of the physical exercise. PLGM system in adolescents with type 1 diabetes was effective to prevent hypoglycemia during and after exercise, irrespective of the PLGM thresholds used.

Adjusting insulin doses in patients with type 1 diabetes who use insulin pump and continuous glucose monitoring: Variations among countries and physicians.

AIMS: To evaluate physicians' adjustments of insulin pump settings based on continuous glucose monitoring (CGM) for patients with type 1 diabetes and to compare these to automated insulin dose adjustments. METHODS: A total of 26 physicians from 16 centres in Europe, Israel and South America participated in the study. All were asked to adjust insulin dosing based on insulin pump, CGM and glucometer downloads of 15 patients (mean age 16.2 ± 4.3 years, six female, mean glycated haemoglobin 8.3 ± 0.9% [66.8 ± 7.3 mmol/mol]) gathered over a 3-week period. Recommendations were compared for the relative changes in the basal, carbohydrate to insulin ratio (CR) and correction factor (CF) plans among physicians and among centres and also between the physicians and an automated algorithm, the Advisor Pro (DreaMed Diabetes Ltd, Petah Tikva, Israel). Study endpoints were the percentage of comparison points for which there was full agreement on the trend of insulin dose adjustments (same trend), partial agreement (increase/decrease vs no change) and full disagreement (opposite trend). RESULTS: The percentages for full agreement between physicians on the trend of insulin adjustments of the basal, CR and CF plans were 41 ± 9%, 45 ± 11% and 45.5 ± 13%, and for complete disagreement they were 12 ± 7%, 9.5 ± 7% and 10 ± 8%, respectively. Significantly similar results were found between the physicians and the automated algorithm. The algorithm magnitude of insulin dose change was at least equal to or less than that proposed by the physicians. CONCLUSIONS: Physicians provide different insulin dose recommendations based on the same datasets. The automated advice of the Advisor Pro did not differ significantly from the advice given by the physicians in the direction or magnitude of the insulin dosing.

Contribution of basal and postprandial hyperglycaemia in type 2 diabetes patients treated by an intensified insulin regimen: Impact of pump therapy in the OPT2mise trial.

AIMS: The relative contribution of basal hyperglycaemia (BHG) and postprandial hyperglycaemia (PPHG) in type 2 diabetes patients treated with multiple daily injections (MDI) of insulin is poorly documented. In this study, the BHG and PPHG of patients from the OPT2mise study who were initially treated with MDI were assessed before randomization and again after 6 months of continuous subcutaneous insulin infusion (CSII). MATERIALS AND METHODS: Blinded continuous glucose monitoring (CGM) data were collected in 259 MDI patients after completion of an 8-week run-in period. The hyperglycaemic area under the curve (AUC) during the 24-hour basal period (AUC-B) and the postprandial period (AUC-P) were compared with analysis of variance based on contribution to total hyperglycaemia in HbA1c groups (Group 1, <8%; Group 2, 8%-8.4%; Group 3, 8.5%-8.9%; Group 4, 9%-9.4%; Group 5, ≥9.5%). Changes in AUC-B and AUC-P were assessed after 6 months of pump therapy in 131 randomized participants with available CGM recordings. RESULTS: In patients undergoing MDI therapy, AUC-B was 21.6% to 54.8% lower in Group 4 to 1 (P = .0138 and P = .0002, respectively) in comparison to Group 5. In contrast, AUC-P did not differ among HbA1c groups (P = .1009). HbA1c correlated with AUC-B, but not with AUC-P. After switching to CSII, AUC-B and AUC-P decreased by 21% and 17%, respectively. When comparing responders with non-responders to CSII therapy, no between-group differences were observed in AUC-B and AUC-P. CONCLUSIONS: Basal hyperglycaemia is the major determinant of overall exposure to hyperglycaemia in type 2 diabetes with MDI failure.

Adjusting Insulin Delivery to Activity (AIDA) clinical trial: Effects of activity-based insulin profiles on glucose control in children with type 1 diabetes.

BACKGROUND: Increased daytime activity in children with type I diabetes mellitus (T1DM) is associated with increased risk of hypoglycemia. OBJECTIVE: To determine whether an automated weekly review of accelerometer, continuous glucose monitoring (CGM), and insulin pump data, could be used to identify children with increased risk of nighttime hypoglycemia and preemptively adjust the nighttime basal insulin profile according to daytime activity. RESEARCH AND DESIGN METHODS: Clinical trial of children with T1DM on insulin pump and CGM therapy. Subjects at risk of nighttime hypoglycemia were identified from regression analysis of daytime step count vs nighttime nadir glucose. If the regression slope was significantly different from zero (P < 0.05) subjects were managed with different algorithm derived nighttime basal insulin profiles following high and low activity days. RESULTS: Twenty children (median age: 12; range: 7-17 years) were enrolled. Regression slopes were significant in 10 children. In these children, baseline nighttime nadir glucose level was lower following high activity days (120 [110-139] vs 152 [130-162] mg/dL, P = 0.004). Use of activity-based nighttime basal profiles produced similar nighttime nadir glucose levels following high and low activity days (136 [123-175] vs 140 [108-180] mg/dL, P = 0.73) with fewer nighttime interventions to correct hypoglycemia (0 [0-0.16] vs 0.15 [0.13-0.22] per night, P = 0.008). CONCLUSION: Children with lower nighttime glucose levels following high daytime activity can be identified using step count data obtained from readily available accelerometers and the nighttime glucose control improved using different activity-based basal profiles.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY 2018 POSITION STATEMENT ON INTEGRATION OF INSULIN PUMPS AND CONTINUOUS GLUCOSE MONITORING IN PATIENTS WITH DIABETES MELLITUS.

This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there are no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician. AACE/ACE Task Force on Integration of Insulin Pumps and Continuous Glucose Monitoring in the Management of Patients With Diabetes Mellitus Chair George Grunberger, MD, FACP, FACE Task Force Members Yehuda Handelsman, MD, FACP, FNLA, MACE Zachary T. Bloomgarden, MD, MACE Vivian A. Fonseca, MD, FACE Alan J. Garber, MD, PhD, FACE Richard A. Haas, MD, FACE Victor L. Roberts, MD, MBA, FACP, FACE Guillermo E. Umpierrez, MD, CDE, FACP, FACE Abbreviations: AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology A1C = glycated hemoglobin BGM = blood glucose monitoring CGM = continuous glucose monitoring CSII = continuous subcutaneous insulin infusion DM = diabetes mellitus FDA = Food & Drug Administration MDI = multiple daily injections T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus SAP = sensor-augmented pump SMBG = self-monitoring of blood glucose STAR 3 = Sensor-Augmented Pump Therapy for A1C Reduction phase 3 trial.

Strict versus liberal insulin therapy in the cardiac surgery patient: An evidence-based practice development, implementation and evaluation project.

BACKGROUND: Hyperglycemia post-cardiac surgery is associated with poor clinical outcomes. Recent studies suggest maintaining liberal glycemic control (<180mg/dL) using a continuous insulin infusion (CII) versus strict control achieves optimal outcomes and prevents hypoglycemia. PURPOSE: To develop, implement and evaluate a nurse managed liberal CII protocol. METHODS: Retrospective review of 144 strict CII patient records and 147 liberal CII patient records. RESULTS: Mean blood glucose was 159.8mg/dL (liberal CII) compared to 143.3mg/dL (strict CII) (p≤0.001). No surgical site infections occurred in either group. Mean ICU length of stay was 4.5days (liberal) versus 4.4days (strict) (p=0.74). Two 30-day mortalities occurred for the liberal cohort compared to no deaths in the strict group (p=0.49). Hypoglycemia incidence within 24h after surgery was 0.1% (liberal) compared to 0.3% (strict) compared to (p=0.16). CONCLUSION: Use of a nurse managed liberal CII resulted in similar outcomes with fewer incidents of hypoglycemia.

Closed-loop for type 1 diabetes - an introduction and appraisal for the generalist.

BACKGROUND: Rapid progress over the past decade has been made with the development of the 'Artificial Pancreas', also known as the closed-loop system, which emulates the feedback glucose-responsive functionality of the pancreatic beta cell. The recent FDA approval of the first hybrid closed-loop system makes the Artificial Pancreas a realistic therapeutic option for people with type 1 diabetes. In anticipation of its advent into clinical care, we provide a primer and appraisal of this novel therapeutic approach in type 1 diabetes for healthcare professionals and non-specialists in the field. DISCUSSION: Randomised clinical studies in outpatient and home settings have shown improved glycaemic outcomes, reduced risk of hypoglycaemia and positive user attitudes. User input and interaction with existing closed-loop systems, however, are still required. Therefore, management of user expectations, as well as training and support by healthcare providers are key to ensure optimal uptake, satisfaction and acceptance of the technology. An overview of closed-loop technology and its clinical implications are discussed, complemented by our extensive hands-on experience with closed-loop system use during free daily living. CONCLUSIONS: The introduction of the artificial pancreas into clinical practice represents a milestone towards the goal of improving the care of people with type 1 diabetes. There remains a need to understand the impact of user interaction with the technology, and its implication on current diabetes management and care.

Optimum bolus wizard settings in insulin pumps in children with Type 1 diabetes.

AIM: To evaluate current insulin pump settings in an optimally regulated paediatric population using bolus wizard. METHODS: We used a retrospective study design to analyse data from 124 children on insulin pump therapy who had optimum HbA1c levels [< 59 mmol/mol (< 7.5%)] and no history of severe hypoglycaemic events. Bolus wizard settings were used to calculate the insulin to carbohydrate factors and insulin sensitivity factors. Multiple regression analysis was used to analyse the variables associated with the calculation factors. RESULTS: Insulin to carbohydrate factor varied from 276 in the youngest group to 424 in the oldest group, and increased according to age. Insulin sensitivity factor was highest in the group aged 6 to < 12 years, with a value of 125. Age, amount of carbohydrates, number of boluses per day and insulin per kg were all significantly associated with both calculation factors. Furthermore, duration of insulin pump treatment was significantly associated with insulin sensitivity factor and percentage bolus/basal was significantly associated with insulin to carbohydrate factor. Gender, diabetes duration and BMI were not associated with any of the calculation factors. CONCLUSION: Optimum insulin pump settings at pump initiation depend on both insulin requirements and use of the pump. Settings need to be individualized because the standardized calculation factors are not constant for children. There is a need to develop specific age- and insulin dose-dependent calculation factors.

Evaluation of a novel continuous glucose monitoring guided system for adjustment of insulin dosing - PumpTune: a randomized controlled trial.

OBJECTIVE: Retrospective continuous glucose monitoring (CGM) can guide insulin pump adjustments, however, interpretation of data and recommending new pump settings is complex and subjective. We aimed to compare the safety and glycaemic profiles of children after their diabetologist or a novel algorithm (PumpTune) adjusted their insulin pump settings. RESEARCH DESIGN AND METHODS: In a randomized cross-over trial of 22 patients aged 6-14 yr with type 1 diabetes with mean Hba1c 7.4% (57 mmol/mol) using CSII, CGM was used over two periods each of 6.5 d to assess percentage time glucose remained within, above and below 3.9-10.0 mmol/L. Before the start of one period pump settings were adjusted by the patient's diabetologist, and before the other insulin pump settings were adjusted by PumpTune. RESULTS: A total of 63.4% of the sensor glucose levels were within target range with PumpTune settings and 57.4% were within range with the clinician settings (p = 0.016). The time spent above target range with PumpTune was 26.9% and with clinician settings was 33.5% (p = 0.021). The time spent below target range with PumpTune was 9.7% and with clinician settings was 9.2% (p = 0.77). The mean number of times when a sensor glucose level <2.75 mmol/L was recorded with PumpTune settings was 2.9 compared with 3.7 with clinician settings (p = 0.39). There were no serious adverse outcomes and no difference in parent-assessed satisfaction. CONCLUSIONS: Automated insulin pump adjustment with PumpTune is feasible and warrants testing in a larger more varied population over a longer time. In this well-controlled group of children, PumpTune achieved a more favorable glucose profile.

Two case reports of retained steel insulin pump infusion set needles.

Insulin pumps are common in the management of type 1 diabetes (T1D). We report two cases of metal insulin infusion set needles which broke off the tubing and remained embedded in the soft tissue of two boys with T1D (five needles in one case, and one needle in the other). The patient with five retained needles was asymptomatic and had a normal physical examination, and the missing needles were only detected using pelvic X-ray; the second patient had only mild discomfort. While these are the first such cases reported in the medical literature, there may be other cases which have gone unnoticed, suggesting the potential need to explore the safety of this product further.

A guideline for the use of variable rate intravenous insulin infusion in medical inpatients.

The present paper summarizes the key recommendations in a recent publication produced by the Joint British Diabetes Societies for Inpatient Care on the use of variable rate i.v. insulin infusion in 'medical' inpatients. The full guideline is available at http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_VRIII.pdf and is designed to be a practical guide that can used by any healthcare professional who manages medical inpatients with hyperglycaemia. Its main aim is to allow variable rate i.v. insulin infusion to be used safely, effectively and efficiently for this specific group of inpatients.

Insulin delivery by injection in children and adolescents with diabetes.

Type 1 diabetes is treated with insulin, which has traditionally been delivered by vial and syringe. However, for many patients, dosing inaccuracy, pain, anxiety, inconvenience, and social acceptability present barriers to this method of administration (1-5). This has contributed to the increased popularity of alternative insulin delivery systems, including pen delivery devices (4, 6). Evidence suggests that discreet devices, such as insulin pens, facilitate adherence to intensive insulin therapy regimens, help improve lifestyle flexibility, and reduce injection pain compared with the conventional syringe-based regimens, as shown in studies in adults and adolescents (7). In addition, compared with the vial and syringe method of insulin administration, pens may provide more accurate dosing - which is particularly important in children - thereby improving short-term blood glucose control and potentially improving long-term outcomes (5, 8). Children, in particular, may benefit from insulin pens that are simple to use as adherence issues may be more evident in this patient group (9). Pens for insulin delivery in children with type 1 diabetes have been used for a long time in Europe, and have recently gained in popularity in many other places around the world (4, 10). Furthermore, the conventional vial and syringe method of insulin delivery is beginning to be considered as obsolete (11). Moreover, there is a continued drive to improve insulin pen technology, to refine and enhance the functionality and usability of these pens. However, despite recent advances in pen design and function, the selection of pens available especially for children is limited.

A framework for specifying safe behavior of the CIIP medical system.

Adequate reliability of algorithms and computations of modern medical systems software is a matter of concern because the system software is in charge of satisfying safety requirements of the system environment, i.e., the patient. This chapter aims to present a framework for specifying the behavior of the Continuous Infusion Insulin Pump (CIIP) safety-critical medical system that satisfies diabetic's safety requirements.

Retrospective analysis and patient satisfaction assessment of insulin pump therapy in patients with type 2 diabetes.

OBJECTIVES: To evaluate and assess glycemic control, total daily insulin requirements, weight, and patient satisfaction after changing from multiple daily injections (MDI) to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 2 diabetes. METHODS: This was a retrospective cross-sectional cohort analysis of an electronic medical records database from a private physician's clinic. Patients over 18 years of age who had type 2 diabetes and who utilized CSII for at least six months were analyzed. Variables of interest included glycosylated hemoglobin, total daily insulin requirements, and weight at the time of conversion from MDI to CSII. Patients were also asked to complete a satisfaction survey comparing MDI to CSII. RESULTS: Thirty patients who met the inclusion criteria were identified. Hemoglobin A1c (HbA1c) decreased from 9.25% ± 2.20 to 7.94% ± 1.65 (P < 0.001) at six months, total daily insulin dose decreased from 1.33 ± 0.66 u/kg/day to 1.08 ± 0.70 u/kg/day (P < 0.001) at six months, and weight increased from 106.66 ± 19.17 kg to 109.75 ± 18.01 kg (P < 0.001). After twelve months, HbA1c did not significantly change and weight returned to baseline; however, total daily insulin dose significantly decreased. 95% of patients preferred CSII therapy to previous injection regimen for various reasons. CONCLUSION: Insulin pump therapy provided better glycemic control and reduced the total amount of insulin utilized. Patients who utilized CSII thought that the treatment was more convenient, less burdensome, and provided better control of fluctuations in blood glucose. CSII was preferred by patients over multiple daily injections.

Initial Basal and Bolus Rates and Basal Rate Variability During Pump Treatment in Children and Adolescents

Objective: Pump-treated children with type 1 diabetes (T1DM) have widely differing basal insulin (BI) infusion profiles for specific periods of the day. The pattern of BI requirements depends on the timing and magnitude of cortisol and growth hormone secretion within each age group. In adolescents and young adults, a decreased insulin sensitivity is seen, particularly in the early morning (dawn phenomenon) and to a lesser extent, in the late afternoon (dusk phenomenon). Different approaches exist for the inititation of basal rates. However, there is a lack of evidence-based recommendation, especially in young children. Usually the basal rates are set equally throughout day and night or the day is divided into tertiles. The aim of this study was to analyze the change of the initial, equally distributed, BI rates over the first year of standard insulin pump therapy. Methods: A total of 154 patients with T1DM, aged between 0 and <21 years at diagnosis, from a single center were documented. Patients were divided into five age groups according to age at pump initiation: group 1, <5 years (n=36); group 2, 5-8 years (n=20); group 3, 8-15 years (n=74); group 4, 15-18 years, (n=19); and group 5, >18 years, (n=5). Distribution of hourly basal rates at the initiation of the pump and at the end of first year were evaluated. Results: Median (range) age and diabetes duration was 14.46 (1.91-26.15) and 7.89 (1.16-17.15) years, respectively. Forty-four percent were male, 56% were female. Mean total insulin dose/kg in the whole cohort at the initiation and after one year of pump therapy was 0.86±0.23 U/kg and 0.78±0.19 U/kg, respectively and differed significantly between each age group (p<0.001; p<0.001). Mean daily basal rate/kg showed significant differences between the five groups (p<0.001). Circadian distribution of BI differed markedly among the five age groups. Conclusion: At the initiation of insulin pump therapy, circadian profiles by age group should be taken into account in pediatric patients to optimize basal rate faster and more easily.