Dataset Information

Safety, efficacy and glucose turnover of reduced prandial boluses during closed-loop therapy in adolescents with type 1 diabetes: a randomized clinical trial.

ABSTRACT: To evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes (T1D).We conducted a randomized crossover study comparing closed-loop therapy with standard prandial insulin boluses versus closed-loop therapy with prandial boluses reduced by 25%. Eight adolescents with T1D [3 males; mean (standard deviation) age 15.9 (1.5) years, glycated haemoglobin 74 (17) mmol/mol; median (interquartile range) total daily dose 0.9 (0.7, 1.1) IU/kg/day] were studied on two 36-h-long visits. In random order, subjects received closed-loop therapy with either standard or reduced insulin boluses administered with main meals (50-80 g carbohydrates) but not with snacks (15-30 g carbohydrates). Stable-label tracer dilution methodology measured total glucose appearance (Ra_total) and glucose disposal (Rd).The median (interquartile range) time spent in target (3.9-10 mmol/l) was similar between the two interventions [74 (66, 84)% vs 80 (65, 96)%; p = 0.87] as was time spent above 10 mmol/l [21.8 (16.3, 33.5)% vs 18.0 (4.1, 34.2)%; p = 0.87] and below 3.9 mmol/l [0 (0, 1.5)% vs 0 (0, 1.8)%; p = 0.88]. Mean plasma glucose was identical during the two interventions [8.4 (0.9) mmol/l; p = 0.98]. Hypoglycaemia occurred once 1.5 h post-meal during closed-loop therapy with standard bolus. Overall insulin delivery was lower with reduced prandial boluses [61.9 (55.2, 75.0) vs 72.5 (63.6, 80.3) IU; p = 0.01] and resulted in lower mean plasma insulin concentration [186 (171, 260) vs 252 (198, 336) pmol/l; p = 0.002]. Lower plasma insulin was also documented overnight [160 (136, 192) vs 191 (133, 252) pmol/l; p = 0.01, pooled nights]. Ra_total was similar [26.3 (21.9, 28.0) vs 25.4 (21.0, 29.2) µmol/kg/min; p = 0.19] during the two interventions as was Rd [25.8 (21.0, 26.9) vs 25.2 (21.2, 28.8) µmol/kg/min; p = 0.46].A 25% reduction in prandial boluses during closed-loop therapy maintains similar glucose control in adolescents with T1D whilst lowering overall plasma insulin levels. It remains unclear whether closed-loop therapy with a 25% reduction in prandial boluses would prevent postprandial hypoglycaemia.

SUBMITTER: Elleri D

PROVIDER: S-EPMC4832358 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety, efficacy and glucose turnover of reduced prandial boluses during closed-loop therapy in adolescents with type 1 diabetes: a randomized clinical trial.

Elleri D D Biagioni M M Allen J M JM Kumareswaran K K Leelarathna L L Caldwell K K Nodale M M Wilinska M E ME Haidar A A Calhoun P P Kollman C C Jackson N C NC Umpleby A M AM Acerini C L CL Dunger D B DB Hovorka R R

Diabetes, obesity & metabolism 20151009 12

<h4>Aims</h4>To evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes (T1D).<h4>Methods</h4>We conducted a randomized crossover study comparing closed-loop therapy with standard prandial insulin boluses versus closed-loop therapy with prandial boluses reduced by 25%. Eight adolescents with T1D [3 males; mean (standard deviation) age 15.9 (1.5) years, glycated haemoglobin 74 (17) mmol/mol ...[more]

PMID: 26257323

Similar Datasets

Project description:The biologic agent ustekinumab is a human monoclonal antibody that binds to the p40 subunit shared by interleukins (ILs) 12 and 23. The antibody is able to prevent binding of cytokines to the IL-12R?1 cell surface receptor and therefore may prevent IL-23 driven activation of the IL-23/Th 17 axis of inflammation. The anti-inflammatory activity has been beneficial in adult psoriasis. Ustekinumab has been approved in the United States for the treatment of adults with psoriasis and psoriatic arthritis. Approval in children and adolescents has not been granted by the US Food and Drug Administration. Subcutaneous injections of ustekinumab are administered at baseline, week 4 and every 12 weeks thereafter, a regimen that is particularly appealing to young patients who do not like more frequent injections at home. The product is attractive because, although it works through an immune system mechanism, the selective activity is such that the drug has not been associated with many of the side effects attributed to other immunosuppressive medications. Case reports of ustekinumab for pediatric psoriasis have shown promising results, and the recent Phase III CADMUS trial tested the agent in adolescents aged 12-17 years with psoriasis, using standard dose 0.75 mg/kg (?60 kg), 45 mg (>60-?100 kg), and 90 mg (>100 kg) or half-standard dosing 0.375 mg/kg (?60 kg), 22.5 mg (>60-?100 kg), and 45 mg (>100 kg) with a loading dosage at week 0 and week 4. Psoriasis area and severity index-75 was achieved in more than three-quarters of patients in full and half dosing by 12 weeks, and psoriasis area and severity index-90 in 54.1% and 61.1% of half and full dosage by 12 weeks, respectively. Ustekinumab was generally well tolerated in adolescents, with some patients developing antibodies, and nasopharyngitis being the major adverse event. Ustekinumab is a promising agent in adolescent psoriasis that appears to be well tolerated. The best monitoring plan and usage in younger patients still remain to be defined.

Project description:BackgroundThe safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring were investigated.MethodsAdolescents (n = 30, ages 14-21 years) and adults (n = 94, ages 22-75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed® 670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase.ResultsAdolescents (mean ± standard deviation [SD] 16.5 ± 2.29 years of age and 7.7 ± 4.15 years of diabetes) used the system for a median 75.8% (interquartile range [IQR] 68.0%-88.4%) of the time (2977 patient-days). Adults (mean ± SD 44.6 ± 12.79 years of age and 26.4 ± 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%-92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA1c levels decreased from 7.7% ± 0.8% to 7.1% ± 0.6% (P < 0.001) and from 7.3% ± 0.9% to 6.8% ± 0.6% (P < 0.001, Wilcoxon signed-rank test), respectively. The proportion of overall in-target (71-180 mg/dL) sensor glucose (SG) values increased from 60.4% ± 10.9% to 67.2% ± 8.2% (P < 0.001) in adolescents and from 68.8% ± 11.9% to 73.8% ± 8.4% (P < 0.001) in adults. During the hotel stay, the proportion of in-target i-STAT® blood glucose values was 67.4% ± 27.7% compared to SG values of 72.0% ± 11.6% for adolescents and 74.2% ± 17.5% compared to 76.9% ± 8.3% for adults. There were no severe hypoglycemic or diabetic ketoacidosis events in either cohort.ConclusionsHCL therapy was safe during in-home use by adolescents and adults and the study phase demonstrated increased time in target, and reductions in HbA1c, hyperglycemia and hypoglycemia, compared to baseline.Trial registrationClinicaltrials.gov identifier: NCT02463097.

Dataset Information

Safety, efficacy and glucose turnover of reduced prandial boluses during closed-loop therapy in adolescents with type 1 diabetes: a randomized clinical trial.

Publications

Safety, efficacy and glucose turnover of reduced prandial boluses during closed-loop therapy in adolescents with type 1 diabetes: a randomized clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets