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Aim: To obtain additional information on the incremental differences between using a sensor-augmented pump (SAP) without automated insulin delivery (AID), using it with predictive low-glucose management (PLGM) or as hybrid closed loop (HCL), in preschool and school children., Methods: We conducted a monocentric, randomized, controlled, two-phase crossover study in 38 children aged 2-6 and 7-14 years. The primary endpoint was the percentage of time in range (TIR) of 70-180 mg/dl. Other continuous glucose sensor metrics, HbA1c, patient-related outcomes (DISABKIDS questionnaire, Fear of Hypoglycaemia Survey) and safety events were also assessed. Results from 2 weeks of SAP, 8 weeks of PLGM and 8 weeks of HCL were compared using a paired t-test or Wilcoxon signed-rank test., Results: Overall, we found a high rate of TIR target (>70%) achievement with HCL in preschool (88%) and school children (50%), with average times in Auto Mode of 93% and 87%, respectively. Preschool children achieved a mean TIR of 73% ± 6% (+8% vs. SAP, +6% vs. PLGM) and school children 69% ± 8% (+15% vs. SAP and + 14% vs. PLGM). Overall, HbA1c improved from 7.4% ± 0.9% to 6.9% ± 0.5% (P = .0002). Diabetes burden and worries and fear of hypoglycaemia remained at low levels, without significant changes versus PLGM. No events of severe hypoglycaemia or diabetic ketoacidosis occurred., Conclusions: Preschool children profit from AID at least as much as those aged 7 years and older. To ensure safe use and prescribing modalities, regulatory approval is also required for young children., (© 2022 John Wiley & Sons Ltd.)

Aim: To investigate whether zinc-free insulin is an effective treatment option for lipoatrophy., Methods: Controlled, randomized, open-label parallel study in young people with type 1 diabetes, pump treatment and lipoatrophy at injection sites. Participants underwent dermatological examination and evaluation of affected areas using ultrasound and magnetic resonance imaging (MRI). After randomization, half of themswitched to insulin glulisine (intervention group) for 6 months. The control group continued their treatment with zinc-containing insulin and switched to insulin glulisine 6 months later. Both groups were followed-up until month 12. Primary endpoint was the increase of the relative thickness of the subcutaneous fat layer of the most atrophic site at 6 months as documented by MRI., Results: Fourteen participants were included into the study. While relative thickness of subcutaneous fat tissue was comparable between intervention (-60% [-98.8 - -17.6], n = 7) and control group (-50% [-72.7 - -1.0], P = .511; median (range), n = 7)at baseline, it improved in the intervention (-14.3% [-85.7-83.3] vs -31.3% (-66.7-0), P = .031), but not in the control group (P = .125) after 6 months. At 12 months, relative fat thickness (P = .003), number (P = .015) and size of most atrophic sites (P = .001) were improved in the intervention group. Number (P = .018) and size of most atrophic sites (P = .008) were also reduced in the control group between 6 and 12 months., Conclusions: Although the present pilot study is based on a small sample, the data give first hint that the use of the zinc-free insulin glulisine may be beneficial in people with diabetes, pump and lipoatrophy., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Aims: Previous DREAM studies demonstrated the safety and efficacy of the CE marked MD-Logic closed-loop system (DreaMed GlucoSitter) in different settings for overnight glycaemic control. The present study aimed to evaluate the system for day and night use for 60 hours during the weekend at home compared to sensor-augmented pump (SAP) therapy in participants with type 1 diabetes., Methods: This was a prospective, multicentre, crossover, controlled study (clinicaltrials.gov NCT01238406). All participants were connected in randomized order for one weekend to SAP therapy or the MD-Logic System. In the intervention arm only, the amount of carbohydrate was entered into the bolus calculator; the rest of insulin delivery was automated and wireless via a tablet computer. The primary endpoint was percentage of glucose values between 70 and 180 mg/dL., Results: The ITT population comprised 48 (19 males, 29 females) adolescents and adults experienced in sensor use: (median, [IQR]): age, 16.1years [13.2-18.5]; diabetes duration, 9.4 years [5.0-12.7]; pump use, 5.4 years [3.1-9.4]; HbA1c, 7.6% [7.0-8.1]. A significant increase in the percentage of time within target range (70-180 mg/dL) (66.6% vs 59.9%, P = 0.002) was observed with the closed-loop system vs control weekends with unchanged percentage of time below 70 mg/dL (2.3% vs 1.5%, P = 0.369). Mean weekend glucose level per participant was significantly lower (153 [142-175] vs 164 [150-186] mg/dL, P = 0.003). No safety signals were observed., Conclusions: The MD-Logic system was safe and associated with better glycaemic control than SAP therapy for day and night use. The absence of remote monitoring did not lead to safety signals in adapting basal rates nor in administration of automated bolus corrections., (© 2018 John Wiley & Sons Ltd.)

Background: A sensor-augmented insulin pump (SAP) using the MiniMed ® 640G system with SmartGuard™ technology allows an automatic stop of insulin delivery based on prediction of low glucose levels. Since pediatric patients are particularly prone to hypoglycemia, this device may offer additional protection beyond conventional sensor-augmented therapy., Methods: This prospective, pediatric multicenter user evaluation assessed 6 weeks of SAP with SmartGuard (threshold setting for hypoglycemia: 70 mg/dL) compared to a preceding period of 2 weeks with SAP only. The primary outcome was the potential reduction in the frequency of hypoglycemic episodes and hypoglycemic intensity (area under the curve [AUC] and time <70 mg/dL)., Results: The study included 24 patients with at least 3 months of insulin pump use (average age: 11.6 ± 5.1 years, 15 female, average type 1 diabetes duration: 7.5 ± 4.2 years, mean ± SD) who had on average 3.2 ± 1.0 predictive suspensions/patient/day. The mean sensor glucose minimum during suspension was 78 ± 6 mg/dL and the average suspension time was 155 ± 47 min/day. Use of SmartGuard in patients treated as per the protocol (n = 18) reduced the number of instances in which the glucose level was <70 mg/dL (1.02 ± 0.52 to 0.72 ± 0.36; P = 0.027), as well as AUC <70 mg/dL (0.76 ± 0.73 to 0.38 ± 0.24; P = 0.027) and the time/day the level fell below 70 mg/dL (73 ± 56 to 31 ± 22 min). The reduction of hypoglycemia was not associated with a significant change in mean glucose concentration (171 ± 26 to 180 ± 19 mg/dL, P = 0.111) and HbA1c (7.5% ± 0.5% to 7.6% ± 0.7%, (P = 0.329). Manual resumption of insulin delivery followed by carbohydrate intake resulted in significantly higher glucose levels 1 h after suspension compared to SmartGuard suspensions with automatic resume (190.8 ± 26.5 vs. 138.7 ± 10.3 mg/dL; P < 0.001)., Conclusions: SmartGuard technology significantly reduced the risk for hypoglycemia in pediatric type 1 diabetes patients without increasing HbA1c. Patients must be educated that when using combining predictive low-glucose insulin suspension technology, extra carbohydrate intake in response to an alarm combined with manual resumption is likely to cause rebound hyperglycemia. The best results were achieved when the user did not interfere with pump operation.

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of long-acting insulin degludec and short-acting insulin aspart. This open-label, Phase 1 study aimed to determine the pharmacodynamic and pharmacokinetic properties of IDegAsp in children (6-11 yr), adolescents (12-17 yr), and adults (18-65 yr) with type 1 diabetes mellitus (T1DM). Thirty-eight subjects received single subcutaneous IDegAsp dosing (0.5 U/kg) immediately before a standardized liquid meal (17.3 g carbohydrates/100 mL; adjusted for body weight) followed by plasma glucose (PG) and pharmacokinetic blood sampling for 36 and 57 h, respectively. There were no apparent differences between age groups in PG lowering effect (AUC PG   baseline,0-6 h,meal, SD ), maximum PG excursion (ΔPG max ,meal, SD ), or maximum PG concentration (PG max ,meal, SD ) after the standardized meal. Estimated ratios (ERs) for total exposure (AUC IAsp ,0-12 h, SD ) and maximum concentration (C max, IAsp , SD ) of IAsp in IDegAsp were children/adults, 1.69 (95% confidence interval, CI: 1.02; 2.80) and 1.66 (95% CI: 1.10; 2.51); adolescents/adults, 1.14 (95% CI: 0.76; 1.69) and 1.16 (95% CI: 0.84; 1.61). ERs for total exposure (AUC IDeg ,0-∞, SD ) and maximum concentration (C max, IDeg , SD ) of IDeg in IDegAsp were children/adults, 1.42 (95% CI: 0.94; 2.16) and 1.38 (95% CI: 1.09; 1.76); adolescents/adults, 1.23 (95% CI: 0.96; 1.58) and 1.16 (95% CI: 0.95; 1.42). IDegAsp was well tolerated across age groups. The fast onset of prandial coverage of IAsp in IDegAsp and the ultra-long pharmacokinetic properties of IDeg in IDegAsp were preserved in children and adolescents. Exposure to IAsp and IDeg seemed to be higher in children vs. adults, but no differences were observed in PG lowering effect. IDegAsp could be an alternative treatment option in children and adolescents with T1DM., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Improvement of nausea by placebo interventions has recently been demonstrated in clinical trials and experimental settings. However, many questions regarding placebo effects on nausea remain unanswered. For example, nausea reduction in women could only be achieved when the placebo intervention was "enhanced" by conditioning, while men responded primarily to verbally suggested improvement. It is unclear whether these findings are generalizable or were due to situational variables. In this pilot study, we investigated the effects of sham acupuncture point stimulation and verbal suggestions on visually-induced nausea in a female population., Methods: In a within-subjects design, 21 healthy female volunteers underwent both a placebo condition and a natural history condition (control condition) in a randomized order on two separate days. On both days, nausea was induced through optokinetic stimulation. On the placebo day, participants received sham acupuncture point stimulation together with positive verbal suggestions of nausea improvement. Expected and perceived nausea severity as well as symptoms of motion sickness were repeatedly assessed., Results: Twenty participants completed both testing days. Participants developed significantly less nausea on the placebo day compared to the control day (p<0.001), and the effect size of placebo-induced nausea reduction was large (partial η 2 =0.71). Symptoms of motion sickness were also reduced (p=0.003). Expectation of nausea decreased following the placebo intervention as compared to no treatment (p=0.030), indicating successful expectancy manipulation., Conclusion: Sham acupuncture point stimulation combined with verbal suggestions induced a significant placebo effect on visually-induced nausea in women., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Poorly designed healthcare systems increase costs and preventable medical errors. To address these issues, systems-based practice (SBP) education provides future physicians with the tools to identify systemic errors and implement quality improvement (QI) initiatives to enhance the delivery of cost-effective, safe and multi-disciplinary care. Although SBP education is being implemented in residency programs and is mandated by the Accreditation Council for Graduate Medical Education (ACGME) as one of its core competencies, it has largely not been integrated into undergraduate medical education. We propose that Medical Student-Faculty Collaborative Clinics (MSFCCs) may be the ideal environment in which to train medical students in SBPs and QI initiatives, as they allow students to play pivotal roles in project development, administration, and management. Here we describe a process of experiential learning that was developed within a newly established MSFCC, which challenged students to identify inefficiencies, implement interventions, and track the results. After identifying bottlenecks in clinic operations, our students designed a patient visit tracker tool to monitor clinic flow and implemented solutions to decrease patient visit times. Our model allowed students to drive their own active learning in a practical clinical setting, providing early and unique training in crucial QI skills.

Aims: This study assesses the impact of using an AP-system at home on fear of hypoglycaemia. In addition, satisfaction and acceptance of the new technology are evaluated., Methods: In a multicentre, multinational study of 75 patients using the MD-Logic AP during four consecutive nights in home setting 59 of them (aged 10-54 years, 54% male, HbA1c 7.89 ± 0.69% [62.72 ± 7.51 mmol/mol], diabetes duration 11.6 ± 8.4 yrs) answered standardized questionnaires (HFS, adapted TAM, and AP satisfaction) before and after using the AP., Results: After experiencing the AP in home setting worries of hypoglycaemia were significantly reduced (before 1.04 ± 0.53 versus after 0.90 ± 0.63; P = 0.017). Perceived ease of use as a measure of acceptance with the AP significantly increased after personal experience (before 4.64 ± 0.94 versus after 5.06 ± 1.09; P = 0.002). The overall satisfaction mean score after using the AP was 3.02 ± 0.54 (range 0-4), demonstrating a high level of satisfaction with this technology., Conclusions: The four-night home-based experience of using MD Logic AP was associated with reduced worries of hypoglycaemia, high level of satisfaction, and increased perceived ease of use of the new technology in children, adolescents, and adults.

Background: Predictive low glucose management (PLGM) may help prevent hypoglycemia by stopping insulin pump delivery based on predicted sensor glucose values., Materials and Methods: Hypoglycemic challenges were simulated using the Food and Drug Administration-accepted glucose simulator with 100 virtual patients. PLGM was then tested with a system composed of a Paradigm(®) insulin pump (Medtronic, Northridge, CA), an Enlite™ glucose sensor (Medtronic), and a BlackBerry(®) (Waterloo, ON, Canada)-based controller. Subjects (n=22) on continuous subcutaneous insulin infusion (five females, 17 males; median [range] age, 15 [range, 14-20] years; median [range] diabetes duration, 7 [2-14] years; median [range] glycated hemoglobin, 8.0% [6.7-10.4%]) exercised until the PLGM system suspended insulin delivery or until the reference blood glucose value (HemoCue(®); HemoCue GmbH, Großostheim, Germany) reached the predictive suspension threshold setting., Results: PLGM reduced hypoglycemia (<70 mg/dL) in silico by 26.7% compared with no insulin suspension, as opposed to a 5.3% reduction in hypoglycemia with use of low glucose suspend (LGS). The median duration of hypoglycemia (time spent <70 mg/dL) with PLGM was significantly less than with LGS (58 min vs. 101 min, respectively; P<0.001). In the clinical trial the hypoglycemic threshold during exercise was reached in 73% of the patients, and hypoglycemia was prevented in 80% of the successful experiments. The mean (±SD) sensor glucose at predictive suspension was 92±7 mg/dL, resulting in a postsuspension nadir (by HemoCue) of 77±22 mg/dL. The suspension lasted for 90±35 (range, 30-120) min, resulting in a sensor glucose level at insulin resumption of 97±19 mg/dL., Conclusions: In silico modeling and early feasibility data demonstrate that PLGM may further reduce the severity of hypoglycemia beyond that already established for algorithms that use a threshold-based suspension.

Insulin degludec (IDeg) is a basal insulin with an ultra-long pharmacokinetic profile in adults that at steady-state produces remarkably flat and stable insulin levels; however, no studies have yet reported on the pharmacokinetic properties of IDeg in subjects younger than 18 years of age. This was a single-centre, randomised, single-dose, double-blind, two-period crossover trial conducted in children (6-11 years), adolescents (12-17 years), and adults (18-65 years) with type 1 diabetes. Subjects received a single subcutaneous dose of 0.4 U/kg IDeg or insulin glargine (IGlar), respectively, on two separate dosing visits, with pharmacokinetic blood sampling up to 72-h postdose. A total of 37 subjects (12 children, 13 adolescents, and 12 adults) completed the trial. Total exposure of IDeg after a single dose (AUCIDeg ,0-∞, SD ) was higher in children compared to adults [estimated ratio children/adults 1.48 (95% confidence interval, CI: 0.98; 2.24)] and in adolescents compared to adults [estimated ratio adolescents/adults 1.33 (95% CI: 1.08; 1.64)]; however, the difference was only statistically significant for the latter comparison. No statistically significant difference in maximum concentration of IDeg (Cmax, IDeg , SD ) was observed. Estimated ratios for Cmax, IDeg , SD were (children/adults) 1.20 (95% CI: 0.90; 1.60) and (adolescents/adults) 1.23 (95% CI: 1.00; 1.51). Simulated mean steady state pharmacokinetic profiles supported a flat and stable IDeg exposure across a 24-h dosing interval. IDeg was detectable in serum for at least 72 h (end of blood sampling period) in all subjects following single dose. In conclusion, the ultra-long pharmacokinetic properties of IDeg observed in adults are preserved in children and adolescents with type 1 diabetes., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate carbohydrate (CARB) and supplementary fat/protein (CFP) counting using normal and dual-wave bolus in pump therapy of children and young people with type 1 diabetes (T1D)., Study Design and Methods: A randomized clinical trial was conducted in 42 patients (age 6-21 yr) with T1D for at least 1 yr (5.2 ± 3.1 yr, mean ± SD) and pump therapy for at least 3 months (3.3 ± 1.8 yr). Standardized test meals (pizza-salami; 50% carbohydrate, 34% fat, 16% protein; corresponding to 33% of age-adjusted daily energy requirement) were given at lunch time on four different days with normal and dual-wave bolus using CARB and CFP counting in a randomized sequence. Sensor-augmented pumps were used for continuous glucose monitoring of 6-h postprandial glucose profiles. Intra-individual comparisons of glucose parameters [area under the curve (AUC) mg/dL × 6 h; average glucose, AV mg/dL] were performed., Results: Using CFP counting, 6-h postprandial glucose AUC (805 ± 261) and AV (137.8 ± 46.2) were significantly lower than AUC (926 ± 285) and AV (160.5 ± 51.9) by CARB counting (p < 0.001, each). CFP counting led to significantly lower postprandial glucose parameters independently from the kind of bolus (normal bolus: ΔAUC 169, p < 0.001; ΔAV 30.6, p < 0.001/dual-wave bolus: ΔAUC 73, p = 0.045, ΔAV 14.8, p = 0.033). Postprandial hypoglycemia episodes (<70 mg/dL) occurred more frequently in CFP than in CARB counting (35.7% vs. 9.5%, p < 0.001). No severe hypoglycemia was reported., Conclusion: In patients with long-term T1D, meal-related insulin dosing based on carbohydrate plus fat/protein counting reduces the postprandial glucose levels (ClinicalTrials.gov NCT01400659)., (© 2012 John Wiley & Sons A/S.)