Background Type 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, and preclinical studies show that it reverses and prevents diabetes. Our aim was to evaluate the safety and efficacy of imatinib in preserving β-cell function in patients with recent-onset type 1 diabetes. MethodsWe did a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients with recentonset type 1 diabetes (<100 days from diagnosis), aged 18-45 years, positive for at least one type of diabetesassociated autoantibody, and with a peak stimulated C-peptide of greater than 0•2 nmol L -¹ on a mixed meal tolerance test (MMTT) were enrolled from nine medical centres in the USA (n=8) and Australia (n=1). Participants were randomly assigned (2:1) to receive either 400 mg imatinib mesylate (4 × 100 mg film-coated tablets per day) or matching placebo for 26 weeks via a computer-generated blocked randomisation scheme stratified by centre. Treatment assignments were masked for all participants and study personnel except pharmacists at each clinical site. The primary endpoint was the difference in the area under the curve (AUC) mean for C-peptide response in the first 2 h of an MMTT at 12 months in the imatinib group versus the placebo group, with use of an ANCOVA model adjusting for sex, baseline age, and baseline C-peptide, with further observation up to 24 months. The primary analysis was by intention to treat (ITT). Safety was assessed in all randomly assigned participants. This study is registered with ClinicalTrials.gov, NCT01781975 (completed).Findings Patients were screened and enrolled between Feb 12, 2014, and May 19, 2016. 45 patients were assigned to receive imatinib and 22 to receive placebo. After withdrawals, 43 participants in the imatinib group and 21 in the placebo group were included in the primary ITT analysis at 12 months. The study met its primary endpoint: the adjusted mean difference in 2-h C-peptide AUC at 12 months for imatinib versus placebo treatment was 0•095 (90% CI -0•003 to 0•191; p=0•048, one-tailed test). This effect was not sustained out to 24 months. During the 24-month follow-up, 32 (71%) of 45 participants who received imatinib had a grade 2 severity or worse adverse event, compared with 13 (59%) of 22 participants who received placebo. The most common adverse events (grade 2 severity or worse) that differed between the groups were gastro intestinal issues (six [13%] partici pants in the imatinib group, primarily nausea, and none in the placebo group) and additional laboratory investigations (ten [22%] participants in the imatinib group and two [9%] in the placebo group). Per the trial protocol, 17 (38%) participants in the imatinib group required a temporary modification in drug dosing and six (13%) permanently discontinued imatinib due to adverse events; five (23%) participants in the placebo group had temporary modifications in dosing and none had a permanent discontinuation du...

Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.

Background: The introduction of insulin pumps with bolus calculators (BCs) has improved glycemic outcomes and quality of life for those with type 1 diabetes. Despite the increased reliance on BCs, the formulas used to derive recommended boluses are not standardized. Our objective was to examine whether recommendations from different pump BCs vary significantly for identical clinical scenarios. Methods: Three commercially available insulin pump BCs were programmed with identical settings and then presented with combinations of blood glucose (BG) and carbohydrates (CHOs) to generate a 4-unit bolus. At one- and two-hour time points, while there was insulin-on-board (IOB) present, we simulated various BG and CHO scenarios in order to compare BC-recommended doses. Results: Differences in suggested doses were noted between BCs, as well as within the same brand. The greatest variation was apparent when BG was below target. Doses suggested by one BC varied depending on whether the IOB resulted from a previous dose given for BG or CHO, while the other two BCs adjusted for total IOB regardless of the source. Conclusions: In this simulation study, there were large differences in recommended doses between BCs due to the unique way each manufacturer incorporates IOB into their formulas as well as the pharmacokinetics used to derive the IOB amount. Providers should be aware that identical pump settings will result in a different dose recommendation for each pump brand and advise patients accordingly.

Background: In 2012, our pediatric hospital transitioned to an electronic medical record system and delegated all inpatient insulin ordering duties to the pediatric endocrine division. This led to a deficit in resident knowledge of blood glucose management, which impacted patient care. To address this gap, we developed a curriculum to facilitate the transition of inpatient subcutaneous insulin ordering privileges to the pediatric residents. Since 2015, several strategies have been implemented to educate the trainees. Our study aim was to identify which strategy optimized retention of this information. Methods: A presentation was developed that included the following topics: types of insulin, formulation of insulin regimens, common pitfalls in dosing, and practice cases. Pre- and posttests with a maximum score of 21 points were distributed. Three separate cohorts completed the curriculum under various settings. Cohort 1 (C1) had residents in groups of 2-15 protected from clinical duties. Cohort 2 (C2) had 27 incoming interns taught during orientation prior to starting clinical duties. Cohort 3 (C3) had trainees of all levels in groups of 4-20 during noon conferences without protection from clinical duties. Data were analyzed with ANOVA using Stata 15 (College Station, TX). Results: Analyses of all the residents (n=162) stratified by level (86 R1, 39 R2, 36 R3) and by cohort (84 C1, 27 C2, 51 C3) were performed. There were baseline differences in knowledge among the trainee levels (mean pretest scores R1 9.8 (0.4), R2 12.1 (0.6), R3 10.9 (0.7), p=0.008); however, after the training session, these differences were mitigated (R1 18.4 (0.3), R2 19.4 (0.3), R3 18.6 (0.5), p=0.1). There was also a slight baseline difference in knowledge among cohorts (mean pretest scores C1 11.2 (0.4), C2 9.2 (0.5), C3 10.1 (0.6), p=0.04). Posttest scores by cohort were significantly different with C1 performing better than C2 and C3 (mean posttest scores C1 19.4 (0.2), C2 18.2 (0.4), C3 17.6 (0.4), p<0.001). There was no difference between C2 and C3 (C1 vs. C2 p=0.04, C1 vs. C3 p <0.001, C2 vs. C3 p=0.6). Discussion: Each cohort attended sessions under different settings, which allowed for evaluation of optimal learning conditions. Notably, there was significant difference in knowledge retention based on the learning environment. C1 had ideal conditions with intimate groups protected from clinical duties and performed the best, whereas C2 and C3 had larger groups with distractions. Thus, effective teaching occurred in small groups in focused settings. Additional posttest analyses may identify knowledge gaps and help customize sessions according to trainee needs. Our experiences highlight the importance of tailoring an environment conducive to learning especially for basic insulin knowledge, which will ultimately improve not only resident training but also quality of patient care.

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