Dual hormone fully closed loop in type 1 diabetes: a randomised trial in the Netherlands - study protocol.

INTRODUCTION: The management of type 1 diabetes (T1DM) has undergone significant advancements with the availability of novel technologies, notably continuous and flash glucose monitoring (CGM and FGM, respectively) and hybrid closed loop (HCL) therapy. The dual hormone fully closed loop (DHFCL) approach with insulin and glucagon infusion has shown promising effects in small studies on glycaemic regulation and quality of life in T1DM. METHODS AND ANALYSIS: The Dual Hormone Fully Closed Loop for Type 1 Diabetes (DARE) study is a non-commercial 12-month open-label, two-arm randomised parallel-group trial. The primary aim of this study is to determine the long-term effects on glycaemic control, patient-reported outcome measurements and cost-effectiveness of the DHFCL compared with usual care, that is, HCL or treatment with multiple daily insulin injections+FGM/CGM. We will include 240 adult patients with T1DM in 14 hospitals in the Netherlands. Individuals will be randomised 1:1 to the DHFCL or continuation of their current care. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Medical Research Ethics Committee NedMec, Utrecht, the Netherlands. Findings will be disseminated through peer-reviewed publications and presentations at local, national and international conferences. TRIAL REGISTRATION NUMBER: NCT05669547.

Bihormonal Artificial Pancreas With Closed-Loop Glucose Control vs Current Diabetes Care After Total Pancreatectomy: A Randomized Clinical Trial.

Importance: Glucose control in patients after total pancreatectomy is problematic because of the complete absence of α- and ß-cells, leading to impaired quality of life. A novel, bihormonal artificial pancreas (BIHAP), using both insulin and glucagon, may improve glucose control, but studies in this setting are lacking. Objective: To assess the efficacy and safety of the BIHAP in patients after total pancreatectomy. Design, Setting, and Participants: This randomized crossover clinical trial compared the fully closed-loop BIHAP with current diabetes care (ie, insulin pump or pen therapy) in 12 adult outpatients after total pancreatectomy. Patients were recruited between August 21 and November 16, 2020. This first-in-patient study began with a feasibility phase in 2 patients. Subsequently, 12 patients were randomly assigned to 7-day treatment with the BIHAP (preceded by a 5-day training period) followed by 7-day treatment with current diabetes care, or the same treatments in reverse order. Statistical analysis was by Wilcoxon signed rank and Mann-Whitney U tests, with significance set at a 2-sided P < .05. Main Outcomes and Measures: The primary outcome was the percentage of time spent in euglycemia (70-180 mg/dL [3.9-10 mmol/L]) as assessed by continuous glucose monitoring. Results: In total, 12 patients (7 men and 3 women; median [IQR] age, 62.5 [43.1-74.0] years) were randomly assigned, of whom 3 did not complete the BIHAP phase and 1 was replaced. The time spent in euglycemia was significantly higher during treatment with the BIHAP (median, 78.30%; IQR, 71.05%-82.61%) than current diabetes care (median, 57.38%; IQR, 52.38%-81.35%; P = .03). In addition, the time spent in hypoglycemia (<70 mg/dL [3.9 mmol/L]) was lower with the BIHAP (median, 0.00% [IQR, 0.00%-0.07%] vs 1.61% [IQR, 0.80%-3.81%]; P = .004). No serious adverse events occurred. Conclusions and Relevance: Patients using the BIHAP after total pancreatectomy experienced an increased percentage of time in euglycemia and a reduced percentage of time in hypoglycemia compared with current diabetes care, without apparent safety risks. Larger randomized trials, including longer periods of treatment and an assessment of quality of life, should confirm these findings. Trial Registration: trialregister.nl Identifier: NL8871.

Fully Closed Loop Glucose Control With a Bihormonal Artificial Pancreas in Adults With Type 1 Diabetes: An Outpatient, Randomized, Crossover Trial.

OBJECTIVE: To demonstrate the performance and safety of a bihormonal (insulin and glucagon) artificial pancreas (AP) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: In this outpatient, randomized, crossover trial, 2-week fully closed loop glucose control (AP therapy) was compared with 2-week open loop control (patient's normal insulin pump therapy with a glucose sensor if they had one). RESULTS: A total of 23 patients were included in the analysis. Time in range (70-180 mg/dL [3.9-10 mmol/L]) was significantly higher during closed loop (median 86.6% of time [interquartile range 84.9-88.5]) compared with open loop (53.9% [49.7-67.2]; P < 0.0001). CONCLUSIONS: Compared with insulin pump therapy, the bihormonal AP provided superior glucose control, without meal or exercise announcements, and was safe in adults with type 1 diabetes.

Acceptance of the Artificial Pancreas: Comparing the Effect of Technology Readiness, Product Characteristics, and Social Influence Between Invited and Self-Selected Respondents.

BACKGROUND: Psychosocial factors that may affect acceptance of artificial pancreas (AP) systems have been investigated in small sample sizes of highly motivated, self-selected persons with type 1 diabetes (T1DM) with a focus on product characteristics. We aimed to develop a valid survey to investigate the association of technology readiness and social influence with AP acceptance in a larger sample, including both self-selected and invited respondents with T1DM. METHODS: An online survey was developed based on established questionnaires. Intention to use the AP was chosen as measure of AP acceptance. T1DM patients who signed up themselves for scientific research into AP systems represented the self-selected group, while patients treated at a teaching hospital represented the invited group. Questionnaire values were compared using independent t-tests and regression analyses. RESULTS: The developed survey showed reliability and validity. The survey was completed by 425 self-selected and 109 invited persons. Intention to use the AP was high in both groups, but was significantly higher among self-selected respondents. In both groups, intention to use the AP was most strongly related to product compatibility, followed by product complexity, technology readiness, and product usefulness among invited respondents; and followed by product usefulness and technology innovativeness among self-selected respondents. CONCLUSIONS: Product characteristics have a stronger relationship with AP acceptance than technology readiness, while social influence does not seem to be associated with AP acceptance. As the (strength of) factors differ between self-selected and invited persons, researchers and product developers should be cautious when relying on self-selected persons with T1DM in the design, development, and testing of AP systems.

A Review of Safety and Design Requirements of the Artificial Pancreas.

As clinical studies with artificial pancreas systems for automated blood glucose control in patients with type 1 diabetes move to unsupervised real-life settings, product development will be a focus of companies over the coming years. Directions or requirements regarding safety in the design of an artificial pancreas are, however, lacking. This review aims to provide an overview and discussion of safety and design requirements of the artificial pancreas. We performed a structured literature search based on three search components-type 1 diabetes, artificial pancreas, and safety or design-and extended the discussion with our own experiences in developing artificial pancreas systems. The main hazards of the artificial pancreas are over- and under-dosing of insulin and, in case of a bi-hormonal system, of glucagon or other hormones. For each component of an artificial pancreas and for the complete system we identified safety issues related to these hazards and proposed control measures. Prerequisites that enable the control algorithms to provide safe closed-loop control are accurate and reliable input of glucose values, assured hormone delivery and an efficient user interface. In addition, the system configuration has important implications for safety, as close cooperation and data exchange between the different components is essential.

[Artificial pancreas for automated glucose control]. / Kunstpancreas voor geautomatiseerde glucoseregulatie.

Strict glucose control is important for patients with diabetes mellitus in order to prevent complications. However, many patients find it difficult to achieve the recommended HbA1c level. The possibility of hypoglycaemia plays an important role in this. The artificial pancreas automates glucose control, improving glucose levels without increasing hypoglycaemic events. The required insulin dose is calculated and administered on the basis of continuous glucose measurements, taking over a large part of the treatment from the patient. Several research groups are working on making this technique suitable for home use. It is expected that the artificial pancreas will become available in the near future. However, effectiveness and safety will have to be investigated in long-term studies. A large number of insulin-dependent patients with diabetes could be eligible for this treatment.