No abstract

Background: The objective of this study was to assess the safety and performance of the Omnipod Ò personalized model predictive control (MPC) algorithm in adults, adolescents, and children aged ‡6 years with type 1 diabetes (T1D) under free-living conditions using an investigational device. Materials and Methods: A 96-h hybrid closed-loop (HCL) study was conducted in a supervised hotel/rental home setting following a 7-day outpatient standard therapy (ST) phase. Eligible participants were aged 6-65 years with A1C <10.0% using insulin pump therapy or multiple daily injections. Meals during HCL were unrestricted, with boluses administered per usual routine. There was daily physical activity. The primary endpoints were percentage of time with sensor glucose <70 and ‡250 mg/dL. Results: Participants were 11 adults, 10 adolescents, and 15 children aged (meanstandard deviation) 28.8 -7.9, 14.3 -1.3, and 9.9 -1.0 years, respectively. Percentage time ‡250 mg/dL during HCL was 4.5% -4.2%, 3.5% -5.0%, and 8.6% -8.8% per respective age group, a 1.6-, 3.4-, and 2.0-fold reduction compared to ST (P = 0.1, P = 0.02, and P = 0.03). Percentage time <70 mg/dL during HCL was 1.9% -1.3%, 2.5% -2.0%, and 2.2% -1.9%, a statistically significant decrease in adults when compared to ST (P = 0.005, P = 0.3, and P = 0.3). Percentage time 70-180 mg/dL increased during HCL compared to ST, reaching significance for adolescents and children: HCL 73.7% -7.5% vs. ST 68.0% -15.6% for adults (P = 0.08), HCL 79.0% -12.6% vs. ST 60.6% -13.4% for adolescents (P = 0.01), and HCL 69.2% -13.5% vs. ST 54.9% -12.9% for children (P = 0.003). Conclusions: The Omnipod personalized MPC algorithm was safe and performed well over 5 days and 4 nights of use by a cohort of participants ranging from youth aged ‡6 years to adults with T1D under supervised freeliving conditions with challenges, including daily physical activity and unrestricted meals.

Youth of minority race/ethnicity have increased markers of poor prognosis of type 1 diabetes at diagnosis and 3 years postdiagnosis, possibly contributing to higher risk of long-term diabetes complications compared with NHWs.

ImportanceIn preclinical studies, thioredoxin-interacting protein overexpression induces pancreatic beta cell apoptosis and is involved in glucotoxicity-induced beta cell death. Calcium channel blockers reduce these effects and may be beneficial to beta cell preservation in type 1 diabetes.ObjectiveTo determine the effect of verapamil on pancreatic beta cell function in children and adolescents with newly diagnosed type 1 diabetes.Design, Setting, and ParticipantsThis double-blind, randomized clinical trial including children and adolescents aged 7 to 17 years with newly diagnosed type 1 diabetes who weighed 30 kg or greater was conducted at 6 centers in the US (randomized participants between July 20, 2020, and October 13, 2021) and follow-up was completed on September 15, 2022.InterventionsParticipants were randomly assigned 1:1 to once-daily oral verapamil (n = 47) or placebo (n = 41) as part of a factorial design in which participants also were assigned to receive either intensive diabetes management or standard diabetes care.Main Outcomes and MeasuresThe primary outcome was area under the curve values for C-peptide level (a measure of pancreatic beta cell function) stimulated by a mixed-meal tolerance test at 52 weeks from diagnosis of type 1 diabetes.ResultsAmong 88 participants (mean age, 12.7 [SD, 2.4] years; 36 were female [41%]; and the mean time from diagnosis to randomization was 24 [SD, 4] days), 83 (94%) completed the trial. In the verapamil group, the mean C-peptide area under the curve was 0.66 pmol/mL at baseline and 0.65 pmol/mL at 52 weeks compared with 0.60 pmol/mL at baseline and 0.44 pmol/mL at 52 weeks in the placebo group (adjusted between-group difference, 0.14 pmol/mL [95% CI, 0.01 to 0.27 pmol/mL]; P = .04). This equates to a 30% higher C-peptide level at 52 weeks with verapamil. The percentage of participants with a 52-week peak C-peptide level of 0.2 pmol/mL or greater was 95% (41 of 43 participants) in the verapamil group vs 71% (27 of 38 participants) in the placebo group. At 52 weeks, hemoglobin A1c was 6.6% in the verapamil group vs 6.9% in the placebo group (adjusted between-group difference, −0.3% [95% CI, −1.0% to 0.4%]). Eight participants (17%) in the verapamil group and 8 participants (20%) in the placebo group had a nonserious adverse event considered to be related to treatment.Conclusions and RelevanceIn children and adolescents with newly diagnosed type 1 diabetes, verapamil partially preserved stimulated C-peptide secretion at 52 weeks from diagnosis compared with placebo. Further studies are needed to determine the longitudinal durability of C-peptide improvement and the optimal length of therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT04233034

Current insulin infusion sets are approved for only 2-3 days. The novel ConvaTec infusion set with Lantern technology is designed to extend infusion set wear time.The goal of this pilot study was to evaluate the duration of wear for this set. This was a pilot safety study in adults with type 1 diabetes using tethered insulin pumps. Participants inserted the set and wore it for 10 days or until failure. Among 24 participants, two were excluded. Forty-five per cent of the sets lasted 10 days. Median wear time was 9.1 (7.1, 10.0) days. Among 12 premature failures, six (50%) involved adhesive failures, four (33%) hyperglycaemia unresponsive to correction, one (8%) hyperglycaemia with ketones and one (8%) infection. Average CGM glucose per day of infusion set wear showed a statistically significant increase over time, while total daily insulin over the same period did not change. In this pilot study, the duration of wear for the novel infusion set exceeded previously reported commercial sets (P < .001). This extended wear technology may eventually allow for a combined glucose sensor and infusion set.CSII, insulin pump therapy, insulin therapy, type 1 diabetes | INTRODUCTIONThe weak link in insulin pump and closed-loop therapy is the insulin infusion set that is inserted under the skin. There is limited information on the interaction between the infusion set, subcutaneous tissue and insulin. The infusion set can become occluded or kinked, and local inflammation and infection around the site can result in insufficient insulin delivery, high glucose levels, ketoacidosis and death. 1,2 There are few studies [3][4][5][6][7] published on the extended use of infusion sets beyond 3 days, although investigation is in progress by Capillary Biomedical (NCT04398030) and Medtronic (NCT04113694). Past studies have tested infusion sets for up to 7 days: Patel et al. reported a median wear time of 6.06 (4.35, 6.98) days, 5 Karlin et al. a least squares mean wear time of 4.12-4.31 days, 6 and Waldenmaier et al. a mean wear time of 6.2 ± 1.5 days. 7 The study conducted by Patel et al. established failure criteria for infusion sets and was a randomized, open-label, crossover study of 20 subjects who wore Teflon catheter (Quick-Set) and steel catheter (Sure-T) infusions set for up to 1 week with no difference in the survival curves of the infusion sets.Length of wear of any infusion set was subject specific, and 30% of failures were secondary to uncorrectable hyperglycaemia, indicating partial catheter occlusion or limitations on insulin absorption in the subcutaneous space. 5 The Karlin study was a multicentre, crossover trial that showed no difference in infusion set survival or mean glucose in 20 individuals with type 1 diabetes wearing the sets in lipohypertrophied and non-lipohypertrophied tissue.Our hypothesis was that the ConvaTec infusion set with Lantern technology, a novel infusion set (Figure 1) with additional slitted