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Background: In type 1 diabetes, carbohydrate counting is the standard of care to determine prandial insulin needs, but it can negatively affect quality of life. We developed a novel insulin-and-pramlintide closed-loop system that replaces carbohydrate counting with simple meal announcements., Methods: We performed a randomised crossover trial assessing 14 days of (1) insulin-and-pramlintide closed-loop system with simple meal announcements, (2) insulin-and-placebo closed-loop system with carbohydrate counting, and (3) insulin-and-placebo closed-loop system with simple meal announcements. Participants were recruited at McGill University Health Centre (Montreal, QC, Canada). Eligible participants were adults (aged ≥18 years) and adolescents (aged 12-17 years) with type 1 diabetes for at least 1 year. Participants were randomly assigned in a 1:1:1:1:1:1 ratio to a sequence of the three interventions, with faster insulin aspart used in all interventions. Each intervention was separated by a 14-45-day wash-out period, during which participants reverted to their usual insulin. During simple meal announcement interventions, participants triggered a prandial bolus at mealtimes based on a programmed fixed meal size, whereas during carbohydrate counting interventions, participants manually entered the carbohydrate content of the meal and an algorithm calculated the prandial bolus based on insulin-to-carbohydrate ratio. Two primary comparisons were predefined: the percentage of time in range (glucose 3·9-10·0 mmol/L) with a non-inferiority margin of 6·25% (non-inferiority comparison); and the mean Emotional Burden subscale score of the Diabetes Distress Scale (superiority comparison), comparing the insulin-and-placebo system with carbohydrate counting minus the insulin-and-pramlintide system with simple meal announcements. Analyses were performed on a modified intention-to-treat basis, excluding participants who did not complete all interventions. Serious adverse events were assessed in all participants. This trial is registered on ClinicalTrials.gov, NCT04163874., Findings: 32 participants were enrolled between Feb 14, 2020, and Oct 5, 2021; two participants withdrew before study completion. 30 participants were analysed, including 15 adults (nine female, mean age 39·4 years [SD 13·8]) and 15 adolescents (eight female, mean age 15·7 years [1·3]). Non-inferiority of the insulin-and-pramlintide system with simple meal announcements relative to the insulin-and-placebo system with carbohydrate counting was reached (difference -5% [95% CI -9·0 to -0·7], non-inferiority p<0·0001). No statistically significant difference was found in the mean Emotional Burden score between the insulin-and-pramlintide system with simple meal announcements and the insulin-and-placebo system with carbohydrate counting (difference 0·01 [SD 0·82], p=0·93). With the insulin-and-pramlintide system with simple meal announcements, 14 (47%) participants reported mild gastrointestinal symptoms and two (7%) reported moderate symptoms, compared with two (7%) participants reporting mild gastrointestinal symptoms on the insulin-and-placebo system with carbohydrate counting. No serious adverse events occurred., Interpretation: The insulin-and-pramlintide system with simple meal announcements alleviated carbohydrate counting without degrading glucose control, although quality of life as measured by the Emotional Burden score was not improved. Longer and larger studies with this novel approach are warranted., Funding: Juvenile Diabetes Research Foundation., Competing Interests: Declaration of interests MAT received speaker honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi. LL received research support from AstraZeneca and Merck; consultant fees from Abbott, Dexcom, Insulet, and Novo Nordisk; payment or honoraria and support for attending meetings or travel from Novo Nordisk; and participated on a data safety monitoring board and advisory board for the National Institutes of Health artificial pancreas programme. MV received research support from Abbott, Bausch Health, and Novo Nordisk; consultant fees from AbbVie, Abbott, Bausch Health, Boehringer Ingelheim, Lifescan, Lyceum, Novo Nordisk, Roche, and Sanofi; and speaker honoraria from Abbott, AbbVie, Bausch Health, Lifescan, Lilly, Merck, Novo Nordisk, Pfizer, Roche, and Sanofi. J-FY received research support from Bayer, Novo Nordisk, Novartis, and Sanofi; consultant fees from Abbott, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Merck, Mylan, Novo Nordisk, and Sanofi; and speaker honoraria from Novo Nordisk and Eli Lilly. NG-P is employed by Tandem Diabetes Care. AH received research support from Adocia, Dexcom, Eli Lilly, and Tandem Diabetes Care; equipment, materials, drugs, medical writing, gifts, or other services from Dexcom, Ypsomed, and Tandem Diabetes Care; consulting fees from Eli Lilly; and intellectual property acquisition fees from Eli Lilly and Bigfoot. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: For people with type 1 diabetes, there is currently no automated insulin delivery system that does not require meal input. We aimed to assess the efficacy of a novel faster-acting insulin aspart (Fiasp) plus pramlintide fully closed-loop system that does not require meal input., Methods: In this open-label, randomised controlled, crossover, non-inferiority trial we compared the Fiasp (Novo Nordisk, Bagsværd, Denmark) plus pramlintide closed-loop system with no meal input (fully artificial pancreas) and the Fiasp-alone closed-loop system with precise carbohydrate counting (hybrid artificial pancreas). Adults (≥18 years) who had a clinical diagnosis of type 1 diabetes for at least 12 months, had glycated haemoglobin 12% or lower, and had been on insulin pump therapy for at least 6 months were enrolled at McGill University Health Centre, Montreal, QC, Canada. The Fiasp plus pramlintide fully closed-loop system delivered pramlintide in a basal-bolus manner with a fixed ratio of 10 μg:U relative to insulin. A research staff member counted the carbohydrate content of meals to input in the hybrid closed-loop system. Participants completed the two full-day crossover interventions in a random order allocated by a computer-generated code implementing a blocked randomisation (block size of four). The primary outcome was the percentage of time spent within the glucose target range (3·9-10·0 mmol/L), with a 6% non-inferiority margin, assessed in all participants who completed both interventions. This trial is registered with ClinicalTrials.gov, NCT03800875., Findings: Between Feb 8, 2019, and Sept 19, 2020, we enrolled 28 adults, of whom 24 completed both interventions and were included in analyses. The percentage of time spent in the target range was 74·3% (IQR 61·5-82·8) with the fully closed-loop system versus 78·1% (66·3-87·5) with the hybrid Fiasp-alone closed-loop system (paired difference 2·6%, 95% CI -2·4 to 12·2; non-inferiority p=0·28). Eight (33%) participants had at least one hypoglycaemia event (<3·3 mmol/L) with the fully closed-loop system compared with 14 (58%) participants with the hybrid closed-loop system (2200-2200 h). Non-mild nausea was reported by three (13%) participants and non-mild bloating by one (4%) participant with the fully closed-loop system compared with zero participants with the hybrid closed-loop system., Interpretation: The Fiasp plus pramlintide fully closed-loop system was not non-inferior to the Fiasp-alone hybrid closed-loop system for the overall percentage of time in the glucose target range. However, participants still spent a high percentage of time within the target range with the fully-closed loop system. Outpatient studies comparing the fully closed-loop hybrid systems with patient-estimated, rather than precise, carbohydrate counting are warranted., Funding: Diabetes Canada., Competing Interests: Declaration of interests AH received research support or grants from Eli Lilly, Adocia, AgaMatrix, and Diabetes Canada; consulting fees and speaker fees or honoraria from Eli Lilly; insulin pumps, glucose sensors, and monitors from Dexcom, Tandem, and Medtronic; and pending patents in the artificial pancreas area (US patent application 16/893,084; US patent application 16/955,191; US patent application 16/608,054). MAT received research support from AgaMatrix, and speaker honoraria from Eli Lilly, Novo Nordisk, Boeringher Ingelheim, Janssen, and AstraZeneca. J-FY received research support or grants from Bayer, Sanofi, and Novo Nordisk and honoraria from Merck, AstraZeneca, Janssen, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medtronic, Abbott, Dexcom, and Sanofi; and participated in advisory boards for Merck, AstraZeneca, Janssen, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medtronic, Abbott, Dexcom, and Sanofi. LL received consulting fees from Dexcom, Insulet, and Novo Nordisk, grants or contracts from Merck and AstraZeneca; participated in advisory boards for the US National Institutes of Health, Novo Nordisk, Insulet, and Dexcom; and participated in data safety monitoring boards for the US National Institutes of Health. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: The first hybrid artificial pancreas (AP) systems with insulin only (mono-hormonal) have recently reached the market while next generations systems are under development including those with glucagon addition (bi-hormonal). Understanding the expectations and impressions of future potential users about AP systems is important for optimal use of this clinically effective emerging technology., Methods and Results: An online survey about AP systems which consisted of 50 questions was addressed to people with type 1 diabetes in the province of Quebec, Canada. Surveys were completed by 123 respondents with type 1 diabetes (54% women, mean (SD) age 40.2 (14.4) y.o., diabetes duration 23.7 (14.1) years, 58% insulin pump users and 43% glucose sensor users). Of the respondents, 91% understood how AP systems work, 79% trusted them with correct insulin dosing, 73% were willing to replace their current treatment with AP and 80% expected improvement in quality of life. Anxiety about letting an algorithm control their glucose levels was expressed by 18% while the option of ignoring or modifying AP instructions was favoured by 88%. As for bi-hormonal AP systems, 83% of respondents thought they would be useful to further reduce hypoglycemic risks., Conclusions: Overall, respondents expressed positive views about AP systems use and high expectations for a better quality of life, glycemic control and hypoglycemia reduction. Data from this survey could be useful to health care professionals and developers of AP systems., Competing Interests: Declaration of competing interest RRL has received research grants from the Canadian Diabetes Association, Astra-Zeneca, Eli Lilly, Cystic Fibrosis Canada, Merck, Novo-Nordisk, and Sanofi-Aventis. He has been a consultant or member of advisory panels of Abbott, Amgen, Astra-Zeneca, Boehringer, Carlina Technology, Eli Lilly, Janssen, Medtronic, Merck, Neomed, Novo-Nordisk, Roche, Sanofi-Aventis, and Takeda. He has received honoraria for conferences by Abbott, Astra-Zeneca, Eli Lilly, Janssen, Medtronic, Merck, Novo-Nordisk, and Sanofi-Aventis. He has received in kind contributions related to closed-loop technology from Animas, Medtronic, and Roche. He also benefits from unrestricted grants for clinical and educational activities from Eli Lilly, Lifescan, Medtronic, Merck, Novo Nordisk, and Sanofi. He holds intellectual property in the field of type 2 diabetes risk biomarkers, catheter life and the closed-loop system. RRL, LL and VM received purchase fees from Eli Lilly in relation with closed-loop technology. LL received consulting fees from Lilly and Dexcom, and received (to institution) research funding from Merck, Astra-zeneca and Sanofi. NT, AQ and ER do not have any competing interests to declare., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: To better understand the dawn phenomenon in type 1 diabetes, we sought to determine its prevalence, timing and magnitude in studies specifically designed to assess basal insulin requirements in patients using insulin pumps., Methods: Thirty-three participants from 2 sensor-augmented insulin pump studies were analyzed. Twenty participants were obtained from a methodologically ideal semiautomated basal analysis trial in which basal rates were determined from repeated fasting tests (the derivation set) and 13 from an artificial pancreas trial in which duration of fasting was variable (the "confirmation" set). Prevalence was determined for the total cohort and for individual trials using the standard definition of an increase in insulin exceeding 20% and lasting ≥90 minutes. Among cases, time of onset and percent change in the magnitude of basal delivery were determined., Results: Seventeen participants (52%) experienced the dawn phenomenon (11 of 20 [55%] in the derivation set and 6 of 13 [46%] in the confirmation set). Time of onset was 3 AM (interquartile range [IQR], 3 to 4:15 AM) in the derivation set and 3 AM (IQR, 3 to 4 AM) in the confirmation set. The magnitude of the dawn phenomenon was a 58.1% (IQR, 28.8% to 110.6%) increase in insulin requirements in the derivation set and 65.5% (IQR, 45.6% to 87.4%) in the confirmation set., Conclusions: The dawn phenomenon occurs in approximately half of patients with type 1 diabetes; when present, it has predictable timing of onset (generally 3 AM) and a substantial, but highly variable, magnitude. These findings imply that optimization of glycemic control requires clinical emphasis on fasted overnight basal insulin assessment., (Copyright © 2019 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Aims: To compare the efficacy of three timings to decrease basal insulin infusion rate to reduce exercise-induced hypoglycaemia in patients with type 1 diabetes (T1D) using pump therapy., Methods: A single-blinded, randomized, 3-way crossover study in 22 adults that had T1D > 1 year and using insulin pump > 3 months (age, 40 ± 15 years; HbA 1c , 56.3 ± 10.2 mmol/mol). Participants practiced three 45-min exercise sessions (ergocyle) at 60% VO 2peak 3 hours after lunch comparing an 80% reduction of basal insulin applied 40 minutes before (T-40), 20 minutes before (T-20) or at exercise onset (T0)., Results: No significant difference was observed for percentage of time spent < 4.0 mmol/L (T-40: 16 ± 25%; T-20: 26 ± 27%; T0: 24 ± 29%) (main outcome) and time spent in target range 4.0-10.0 mmol/L (T-40: 63 ± 37%; T-20: 66 ± 25%; T0: 65 ± 31%). With T-40 strategy, although not significant, starting blood glucose (BG) was higher (T-40: 8.6 ± 3.6 mmol/L; T-20: 7.4 ± 2.5 mmol/L ; T0: 7.4 ± 2.7 mmol/L), fewer patients needed extra carbohydrates consumption prior to exercise for BG < 5.0 mmol/L (T-40: n = 3; T-20: n = 5; T0: n = 6) as well as during exercise for BG < 3.3 mmol/L [T-40: n = 6 (27%); T-20: n = 12 (55%); T0: n = 11 (50%)] while time to first hypoglycaemic episode was delayed (T-40: 28 ± 14 min; T-20: 24 ± 10 min; T0: 22 ± 11 min)., Conclusion: Decreasing basal insulin infusion rate by 80% up to 40 minutes before exercise onset is insufficient to reduce exercise-induced hypoglycaemia., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Aims: Mild-to-moderate hypoglycemia (blood glucose < 4.0 mmol/L) is recommended to be treated with 15 g of carbohydrates and to repeat the treatment if hypoglycemia persists after 15 min. This recommendation was established before intensive insulin therapy and based on studies using insulin with different pharmacokinetic profiles from actual insulin analogs showing that 15 g of glucose increases blood glucose by ~ 1.5 mmol/L in 15 min. We aimed to explore the effect of current recommended treatment of mild-to-moderate hypoglycemia in type 1 diabetes (T1D) participants and factors associated with treatment effectiveness., Methods: This is a secondary analysis from three observational inpatient studies with a standardized and supervised treatment (16 g carbohydrates) of hypoglycemia (< 3.3 mmol/L with symptoms or < 3.0 mmol/L without symptom) in participants (47 adults-10 adolescents) with T1D using continuous subcutaneous insulin infusion ("insulin pumps"; CSII))., Results: Twenty-seven participants presented a total of 48 hypoglycemia episodes treated by a single intake of 16 g of carbohydrates. Time required for normoglycemia recovery was 19.5 ± 12.0 min. The rise in plasma glucose following treatment was 0.85 ± 0.66 mmol/L in 15 min. Eighteen episodes (38%) were resolved (> 4.0 mmol/L) 15-min post-treatment. Glycemia at the time of treatment (< 3.2 mmol/L; p < 0.001) and a higher proportion of total daily insulin from basal doses (p = 0.03) were associated with a slower post-treatment plasma glucose rise., Conclusions: These results raise the possibility that sixteen grams of carbohydrates could be insufficient to treat a large proportion of hypoglycemia episodes in T1D patients treated with CSII. Factors affecting treatment effectiveness need to be investigated.

Background: The dual-hormone (insulin and glucagon) artificial pancreas may be justifiable in some, but not all, patients. We sought to compare dual- and single-hormone artificial pancreas systems in patients with hypoglycemia unawareness and documented nocturnal hypoglycemia., Methods: We conducted a randomized crossover trial comparing the efficacy of dual- and single-hormone artificial pancreas systems in controlling plasma glucose levels over the course of one night's sleep. We recruited 18 adult participants with hypoglycemia unawareness and 17 participants with hypoglycemia awareness, all of whom had documented nocturnal hypoglycemia during 2 weeks of screening. Outcomes were calculated using plasma glucose., Results: In participants with hypoglycemia unawareness, the median (interquartile range [IQR]) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on dual-hormone artificial pancreas nights and 0% (0-10) on single-hormone artificial pancreas nights (P = 0.20). Additionally, participants with hypoglycemia unawareness experienced two hypoglycemic events (<3.0 mmol/L) on dual-hormone artificial pancreas nights and three hypoglycemic events on single-hormone artificial pancreas nights. In participants with hypoglycemia awareness, the median (IQR) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on both dual- and single-hormone artificial pancreas nights. Hypoglycemia awareness participants experienced zero hypoglycemic events on dual-hormone artificial pancreas nights and one event on single-hormone artificial pancreas nights., Discussion: In this study, dual-hormone and single-hormone systems performed equally well in preventing nocturnal hypoglycemia in participants with hypoglycemia unawareness. Longer studies over the course of multiple days and nights may be needed to explore possible specific benefits in this population. ClinicalTrials.gov No. NCT02282254.

Postprandial glucose control remains challenging for patients with type 1 diabetes (T1D). A simplified meal bolus approach with a dual-hormone (insulin and glucagon) closed-loop system (DH-CLS) has been tested; yet, the impact of categorization errors with this strategy is unknown. The objective was to compare, in a randomized controlled inpatient trial, DH-CLS with the simplified meal bolus approach for two different meals properly categorized or overestimated. We tested, in patients with T1D, the simplified strategy with two standardized breakfasts (n = 10 per meal) adequately categorized or overestimated: (1) 75 g and (2) 45 g of carbohydrate. No difference was observed for percentage of time <4.0 mmol/L over a 4-hour post-meal period (primary outcome; median [IQR]: 0[0-0] vs. 0[0-0] for both comparisons, p = 0.47 and 0.31 for the 75 g and 45 g meals, respectively). Despite higher meal insulin boluses with overestimation for both meals (9.2 [8.2-9.6] vs. 8.1 [7.3-9.1] U and 8.4 [7.2-10.4] vs. 4.8 [3.7-5.6] U; p < 0.05), mean glycemia, percentage of time in target range and glucagon infusion did not differ. Additional scenarios were tested in silico with comparable results. These results suggest that the DH-CLS with a simplified meal bolus calculation is probably able to avoid hypoglycemia in the event of meal size misclassification.

In children and adolescents, treatments for type 1 diabetes (T1D) have recently evolved with the introduction of the insulin pump. However, little is known about how a pump is associated with physical activity (PA) patterns. The goal of the study was to examine the activity profile of Canadian children and adolescents with T1D according to their insulin treatment (pump vs. injections), as well as barriers to exercise and parental lifestyle habits. A self-administered questionnaire was completed by 188 subjects with T1D aged 6 to 17 and their parents at the endocrinology clinic of Sainte-Justine's University Hospital Center (Montreal, Canada). Sixty percent of patients used an insulin pump. There were no significant differences in any components of the PA profile, sedentary habits, and exercise barriers between subjects using injections and those using a pump. Fear of hypoglycemia was the main PA barrier in both treatment groups. A more diverse PA practice by parents was associated with more moderate-to-vigorous PA and less screen time in adolescents. In conclusion, type of treatment was not associated with more activity in pediatric patients with T1D and a varied parental PA profile was the main factor of interest for healthier habits in adolescents with T1D., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The role of glucagon in the pathophysiology of diabetes has long been recognized, although its approved clinical use has so far been limited to the emergency treatment of severe hypoglycaemia. A novel use of glucagon as intermittent mini-boluses is proposed in the dual-hormone version (insulin and glucagon) of the external artificial pancreas. Short-term studies suggest that the incorporation of glucagon into artificial pancreas systems has the potential to further decrease hypoglycaemic risk and improve overall glucose control; however, the potential long-term safety and benefits also need to be investigated given the recognized systemic effects of glucagon. In the present report, we review the available animal and human data on the physiological functions of glucagon, as well as its pharmacological use, according to dosing and duration (acute and chronic). Along with its main role in hepatic glucose metabolism, glucagon affects the cardiovascular, renal, pulmonary and gastrointestinal systems. It has a potential role in weight reduction through its central satiety function and its role in increasing energy expenditure. Most of the pharmacological studies investigating the effects of glucagon have used doses exceeding 1 mg, in contrast to the mini-boluses used in the artificial pancreas. The available data are reassuring but comprehensive human studies using small but chronic glucagon doses that are close to the physiological ranges are lacking. We propose a list of variables that could be monitored during long-term trials of the artificial pancreas. Such trials should address the questions about the risk-benefit ratio of chronic glucagon use., (© 2016 John Wiley & Sons Ltd.)

Background: Single- and dual-hormone closed-loop systems can improve glycemic control and have the potential to reduce carbohydrate-counting burden for patients with type 1 diabetes; however, simplification of meal insulin calculation should not compromise glycemic control., Methods: We compared in a randomized outpatient pilot trial: (1) a single-hormone closed-loop system accompanied with carbohydrate-content matched boluses versus accompanied with a simplified meal bolus strategy, and (2) a dual-hormone closed-loop system accompanied with carbohydrate-content matched boluses versus accompanied with a simplified meal bolus strategy. Carbohydrate-matched boluses were based on the participant's carbohydrate meal content estimation whereas the simplified strategy involved the selection, by participants, of a semi-quantitative meal carbohydrate-content size: snack, regular, large, or very large meal. Each participant also underwent sensor-augmented pump therapy. Basal insulin delivery was more aggressive with the simplified bolus. The primary outcome was mean sensor glucose level over a 15-h daytime period., Results: Twelve participants were recruited (48.2 ± 16.0 years old; HbA1c 7.4% ± 0.9%) to compare the two bolus strategies during single- and dual-hormone closed-loop delivery. A similar mean sensor glucose level (15 h) was achieved with the carbohydrate-matched boluses and simplified strategy using single-hormone (median [interquartile]: 7.6 [7.2-8.1] vs. 8.0 [7.0-8.6] mmol/L; P = 0.90) and dual-hormone closed-loop systems (7.6 [6.7-9.1] vs. 7.0 [6.4-8.2] mmol/L; P = 0.08). Exploratory analyses showed that, as compared with sensor-augmented pump therapy, there was an increased time spent in hypoglycemia with the simplified strategy but not with the carbohydrate-matched boluses., Conclusions: Though the algorithm employed in this pilot study may lead to an increased risk for hypoglycemia, this strategy has the potential to reduce the carbohydrate-counting burden in patients with type 1 diabetes while generally maintaining adequate glucose control. Longer outpatient studies with an improved algorithm are needed.

Context: The added benefit of glucagon in artificial pancreas systems for overnight glucose control in type 1 diabetes has not been fully explored., Objective: The objective of the study was to compare the efficacy of dual-hormone (insulin and glucagon) artificial pancreas, single-hormone (insulin alone) artificial pancreas, and conventional insulin pump therapy., Design: This study was a three-center, three-arm, open-label, randomized, crossover controlled trial involving three interventions, each applied over a night after a high carbohydrate/high fat meal and a second after exercise to mimic real-life glycemic excursions., Setting: The study was conducted in a home setting., Patients: Twenty-eight type 1 diabetes participants (21 adults and seven adolescents) participated in the study., Interventions: Dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional pump therapy was activated from 9:00 PM to 7:00 AM., Main Outcome: The main outcome was a proportion of time in target (4-8 mmol/L) by continuous glucose monitoring from 11:00 PM to 7:00 AM. Analysis was by intention to treat., Results: The median (interquartile range) percentage of time-in-target glucose range was 47% (36%-71%) for conventional therapy, higher on both single-hormone (76% [65%-91%], P < .001) and dual-hormone artificial pancreas (81 [68%-93%], P < .001). The median (interquartile range) time spent below 4 mmol/L was 14% (4%-28%) for conventional therapy, lower on both single-hormone (5% [0%-13%], P = .004) and dual-hormone artificial pancreas (1% [0%-8%], P < .001). There were 14 hypoglycemic events on conventional therapy compared with six incidences on the single-hormone artificial pancreas (P = .059) and three incidences on the dual-hormone artificial pancreas (P = .017). None of these outcomes differed significantly between single- and dual-hormone configurations., Conclusions: Single- and dual-hormone artificial pancreas systems both provided better glucose control than conventional therapy. Although the dual-hormone configuration did not increase overnight time-in-target glucose levels, an effect on lowering hypoglycemia risk cannot be ruled out.

Background: The artificial pancreas is an emerging technology for the treatment of type 1 diabetes and two configurations have been proposed: single-hormone (insulin alone) and dual-hormone (insulin and glucagon). We aimed to delineate the usefulness of glucagon in the artificial pancreas system., Methods: We did a randomised crossover trial of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy (continuous subcutaneous insulin infusion) in participants aged 12 years or older with type 1 diabetes. Participants were assigned in a 1:1:1:1:1:1 ratio with blocked randomisation to the three interventions and attended a research facility for three 24-h study visits. During visits when the patient used the single-hormone artificial pancreas, insulin was delivered based on glucose sensor readings and a predictive dosing algorithm. During dual-hormone artificial pancreas visits, glucagon was also delivered during low or falling glucose. During conventional insulin pump therapy visits, patients received continuous subcutaneous insulin infusion. The study was not masked. The primary outcome was the time for which plasma glucose concentrations were in the target range (4·0-10·0 mmol/L for 2 h postprandially and 4·0-8·0 mmol/L otherwise). Hypoglycaemic events were defined as plasma glucose concentration of less than 3·3 mmol/L with symptoms or less than 3·0 mmol/L irrespective of symptoms. Analysis was by modified intention to treat, in which we included data for all patients who completed at least two visits. A p value of less than 0·0167 (0·05/3) was regarded as significant. This trial is registered with ClinicalTrials.gov, number NCT01754337., Findings: The mean proportion of time spent in the plasma glucose target range over 24 h was 62% (SD 18), 63% (18), and 51% (19) with single-hormone artificial pancreas, dual-hormone artificial pancreas, and conventional insulin pump therapy, respectively. The mean difference in time spent in the target range between single-hormone artificial pancreas and conventional insulin pump therapy was 11% (17; p=0·002) and between dual-hormone artificial pancreas and conventional insulin pump therapy was 12% (21; p=0·00011). There was no difference (15; p=0·75) in the proportion of time spent in the target range between the single-hormone and dual-hormone artificial pancreas systems. There were 52 hypoglycaemic events with conventional insulin pump therapy (12 of which were symptomatic), 13 with the single-hormone artificial pancreas (five of which were symptomatic), and nine with the dual-hormone artificial pancreas (0 of which were symptomatic); the number of nocturnal hypoglycaemic events was 13 (0 symptomatic), 0, and 0, respectively., Interpretation: Single-hormone and dual-hormone artificial pancreas systems both provided better glycaemic control than did conventional insulin pump therapy. The single-hormone artificial pancreas might be sufficient for hypoglycaemia-free overnight glycaemic control., Funding: Canadian Diabetes Association; Fondation J A De Sève; Juvenile Diabetes Research Foundation; and Medtronic., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: We compared post-breakfast closed-loop glucose control either matched with a carbohydrate-matching bolus or a weight-dependent bolus., Methods: Twelve adults with type 1 diabetes consumed a 75 g CHO breakfast on two occasions. In random order, the breakfast was accompanied by a full carbohydrate-matching insulin bolus (8.30 U [7.50 U-11.50 U]) or a partial weight-dependent insulin bolus (0.047 U/kg; 3.45 U [2.95 U-3.75 U]). Postprandial glucose was regulated by sensor-responsive insulin and glucagon delivery., Results: Glucose control after the weight-dependent bolus was safe and feasible (glucose values returned to pre-prandial levels after 5 h). However, 5-hr incremental area under the curve and percentage of time above 10 mmol/L were lower after the full bolus compared to the partial bolus (IAUC, 2.1 [0.8-4.2] mmol/L/hr vs 8.3 [6.5-11.4] mmol/L/hr; time in hyperglycaemia, 24% [6%-29%] vs 50% [25%-63%]; P < 0.001)., Conclusions: Post-breakfast closed-loop glucose control without carbohydrate counting, but based on weight-dependent bolus is feasible but a carbohydrate-matching bolus provides better glucose control., Clinical Trial Registry: NCT01519102., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Most patients with type 1 diabetes do not achieve their glycemic targets. We aimed to assess the efficacy of glucose-responsive insulin and glucagon closed-loop delivery for controlling glucose levels in adults with type 1 diabetes., Methods: We conducted a randomized crossover trial involving 15 adults with type 1 diabetes, comparing standard insulin-pump therapy with dual-hormone, closed-loop delivery. Patients were admitted twice to a clinical research facility and received, in random order, both treatments. Each 15-hour visit (from 1600 to 0700) included an evening exercise session, followed by a medium-sized meal, a bedtime snack and an overnight stay. During visits that involved closed-loop delivery, basal insulin and glucagon miniboluses were delivered according to recommendations based on glucose sensor readings and a predictive dosing algorithm at 10-minute intervals. During visits involving standard insulin-pump therapy (control visits), patients used conventional treatment., Results: Dual-hormone closed-loop delivery increased the percentage of time for which patients' plasma glucose levels were in the target range (median 70.7% [interquartile range (IQR) 46.1%-88.4%] for closed-loop delivery v. 57.3% [IQR 25.2%-71.8%] for control, p = 0.003) and decreased the percentage of time for which plasma glucose levels were in the low range (bottom of target range [< 4.0 mmol/L], 0.0% [IQR 0.0%-3.0%] for closed-loop delivery v. 10.2% [IQR 0.0%-13.0%] for control, p = 0.01; hypoglycemia threshold [< 3.3 mmol/L], 0.0% [IQR 0.0%-0.0%] for closed-loop delivery v. 2.8% [IQR 0.0%-5.9%] for control, p = 0.006). Eight participants (53%) had at least 1 hypoglycemic event (plasma glucose < 3.0 mmol/L) during standard treatment, compared with just 1 participant (7%) during closed-loop treatment (p = 0.02)., Interpretation: Dual-hormone, closed-loop delivery guided by advanced algorithms improved short-term glucose control and reduced the risk of hypoglycemia in a group of 15 adults with type 1 diabetes., Trial Registration: ClinicalTrials.gov, no. NCT01297946.