Randomized Trial of the Insulin-Only iLet Bionic Pancreas for the Treatment of Cystic Fibrosis- Related Diabetes.

Objective: Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis and adds significant morbidity and treatment burden. We evaluated the safety and efficacy of automated insulin delivery with the iLet bionic pancreas (BP) in adults with CFRD in a single-center, open-label, random-order, crossover trial.

Research Design And Methods: Twenty participants with CFRD were assigned in random order to 14 days each on the BP or their usual care (UC).

Psychosocial Impact of the Insulin-Only iLet Bionic Pancreas for Adults, Youth, and Caregivers of Youth with Type 1 Diabetes.

To evaluate the psychosocial impact and user experience for the insulin-only configuration of iLet bionic pancreas (BP) in persons 6-83 years years of age with type 1 diabetes. In this multicenter, randomized controlled, 13-week trial, 275 adults (221 randomly assigned to the BP group and 54 to the standard of care [SC] group) and 165 youth and their caregivers (112 randomly assigned to the BP group and 53 to the SC group) completed psychosocial questionnaires at baseline, mid-study, and the end of the trial. In all age groups, most participants would recommend using the BP, including those with previous experience using automated insulin delivery devices.

Utility and Safety of Backup Insulin Regimens Generated by the Bionic Pancreas: A Randomized Study.

The bionic pancreas (BP) is initialized with body weight only and doses insulin autonomously without carbohydrate counting, instead using qualitative meal announcements. In case of device malfunction, the BP generates and continuously updates backup insulin doses for injection or pump users, including long-acting insulin dose, a four-period basal insulin profile, short-acting meal doses, and a glucose correction factor. Following a 13-week trial in type 1 diabetes, participants using the BP (6-83 years) completed 2-4 days, in which they were randomly assigned to their prestudy insulin regimen ( = 147) or to follow BP-provided guidance ( = 148).

The Insulin-Only Bionic Pancreas Pivotal Trial Extension Study: A Multi-Center Single-Arm Evaluation of the Insulin-Only Configuration of the Bionic Pancreas in Adults and Youth with Type 1 Diabetes.

To evaluate a transition from standard-of-care (SC) management of type 1 diabetes (any insulin delivery method including hybrid closed-loop systems plus real-time continuous glucose monitoring [CGM]) to use of the insulin-only configuration of the iLet bionic pancreas (BP) in 90 adults and children (age 6-71 years). After the SC group completed the randomized controlled trial (RCT) portion of the Insulin-Only BP Pivotal Trial, 90 of the 107 participants participated in a 13-week study using the BP. The key outcomes were change from baseline in HbA1c and CGM metrics after 13 weeks on the BP.

Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial.

To evaluate the insulin-only configuration of the iLet bionic pancreas (BP) in youth 6-17 years old with type 1 diabetes (T1D). In this multicenter, randomized, controlled trial, 165 youth with T1D (6-17 years old; baseline HbA1c 5.8%-12.

A Multicenter Randomized Trial Evaluating the Insulin-Only Configuration of the Bionic Pancreas in Adults with Type 1 Diabetes.

To evaluate the insulin-only configuration of the iLet bionic pancreas (BP) using insulin aspart or insulin lispro in adults with type 1 diabetes (T1D). In this multicenter, randomized, controlled trial, 161 adults with T1D (18-79 years old, baseline HbA1c 5.5%-13.

A Multicenter Randomized Trial Evaluating Fast-Acting Insulin Aspart in the Bionic Pancreas in Adults with Type 1 Diabetes.

To evaluate the insulin-only configuration of the iLet bionic pancreas (BP) using fast-acting insulin aspart (Fiasp) in adults with type 1 diabetes (T1D). In this multicenter, randomized trial, 275 adults with T1D (18-83 years old, baseline HbA1c 5.3%-14.

Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes.

Background: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.

Methods: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring).

The Bihormonal Bionic Pancreas Improves Glycemic Control in Individuals With Hyperinsulinism and Postpancreatectomy Diabetes: A Pilot Study.

Objective: To determine whether the bihormonal bionic pancreas (BHBP) improves glycemic control and reduces hypoglycemia in individuals with congenital hyperinsulinism (HI) and postpancreatectomy diabetes (PPD) compared with usual care (UC).

Research Design And Methods: Ten subjects with HI and PPD completed this open-label, crossover pilot study. Coprimary outcomes were mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration <3.

Feasibility Studies of an Insulin-Only Bionic Pancreas in a Home-Use Setting.

Background: We tested the safety and performance of the "insulin-only" configuration of the bionic pancreas (BP) closed-loop blood-glucose control system in a home-use setting to assess glycemic outcomes using different static and dynamic glucose set-points.

Method: This is an open-label non-randomized study with three consecutive intervention periods. Participants had consecutive weeks of usual care followed by the insulin-only BP with (1) an individualized static set-point of 115 or 130 mg/dL and (2) a dynamic set-point that automatically varied within 110 to 130 mg/dL, depending on hypoglycemic risk.

Automated glycemic control with the bionic pancreas in cystic fibrosis-related diabetes: A pilot study.

Cystic fibrosis-related diabetes (CFRD) is the most common extrapulmonary manifestation of cystic fibrosis. The current standard of care for CFRD involves treatment with insulin, typically via multiple daily injections. We conducted a small pilot study comparing usual care with automated glycemic control using the bihormonal (insulin and glucagon) and insulin-only configurations of the bionic pancreas.

A Comparison of Time Delay in Three Continuous Glucose Monitors for Adolescents and Adults.

Background: The physiologic delay in glucose diffusion from the blood to the interstitial fluid and instrumental factors contribute to the delay between changes in plasma glucose (PG) and measurements made by continuous glucose monitors (CGMs). This study compared the duration of this delay for three CGMs.

Methods: A total of 24 healthy adolescent and adult subjects with type 1 diabetes wore three CGM devices simultaneously for 48 hours: Dexcom G4 Platinum, Abbott Navigator, and Medtronic Enlite.

Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial.

Background: The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity.

Methods: We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA.

Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial.

Background: The safety and efficacy of continuous, multiday, automated glycaemic management has not been tested in outpatient studies of preadolescent children with type 1 diabetes. We aimed to compare the safety and efficacy of a bihormonal bionic pancreas versus conventional insulin pump therapy in this population of patients in an outpatient setting.

Methods: In this randomised, open-label, crossover study, we enrolled preadolescent children (aged 6-11 years) with type 1 diabetes (diagnosed for ≥1 year) who were on insulin pump therapy, from two diabetes camps in the USA.

Outpatient glycemic control with a bionic pancreas in type 1 diabetes.

Background: The safety and effectiveness of automated glycemic management have not been tested in multiday studies under unrestricted outpatient conditions.

Methods: In two random-order, crossover studies with similar but distinct designs, we compared glycemic control with a wearable, bihormonal, automated, "bionic" pancreas (bionic-pancreas period) with glycemic control with an insulin pump (control period) for 5 days in 20 adults and 32 adolescents with type 1 diabetes mellitus. The automatically adaptive algorithm of the bionic pancreas received data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon.

A comparative effectiveness analysis of three continuous glucose monitors: the Navigator, G4 Platinum, and Enlite.

The effectiveness and safety of continuous glucose monitors (CGMs) is dependent on their accuracy and reliability. The objective of this study was to compare 3 CGMs in adult and pediatric subjects with type 1 diabetes under closed-loop blood-glucose (BG) control. Twenty-four subjects (12 adults) with type 1 diabetes each participated in one 48-hour closed-loop BG control experiment.

Autonomous and continuous adaptation of a bihormonal bionic pancreas in adults and adolescents with type 1 diabetes.

Context: A challenge for automated glycemic control in type 1 diabetes (T1D) is the large variation in insulin needs between individuals and within individuals at different times in their lives.

Objectives: The objectives of the study was to test the ability of a third-generation bihormonal bionic pancreas algorithm, initialized with only subject weight; to adapt automatically to the different insulin needs of adults and adolescents; and to evaluate the impact of optional, automatically adaptive meal-priming boluses.

Design: This was a randomized controlled trial.

A comparative effectiveness analysis of three continuous glucose monitors.

Objective: To compare three continuous glucose monitoring (CGM) devices in subjects with type 1 diabetes under closed-loop blood glucose (BG) control.

Research Design And Methods: Six subjects with type 1 diabetes (age 52 ± 14 years, diabetes duration 32 ± 14 years) each participated in two 51-h closed-loop BG control experiments in the hospital. Venous plasma glucose (PG) measurements (GlucoScout, International Biomedical) obtained every 15 min (2,360 values) were paired in time with corresponding CGM glucose (CGMG) measurements obtained from three CGM devices, the Navigator (Abbott Diabetes Care), the Seven Plus (DexCom), and the Guardian (Medtronic), worn simultaneously by each subject.

Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas.

Objective: To test whether safe and effective glycemic control could be achieved in type 1 diabetes using a bihormonal bionic endocrine pancreas driven by a continuous glucose monitor in experiments lasting more than two days and including six high-carbohydrate meals and exercise as challenges to glycemic control.

Research Design And Methods: Six subjects with type 1 diabetes and no endogenous insulin secretion participated in two 51-h experiments. Blood glucose was managed with a bionic endocrine pancreas controlling subcutaneous delivery of insulin and glucagon with insulin pumps.

Efficacy determinants of subcutaneous microdose glucagon during closed-loop control.

Background: During a previous clinical trial of a closed-loop blood glucose (BG) control system that administered insulin and microdose glucagon subcutaneously, glucagon was not uniformly effective in preventing hypoglycemia (BG<70 mg/dl). After a global adjustment of control algorithm parameters used to model insulin absorption and clearance to more closely match insulin pharmacokinetic (PK) parameters observed in the study cohort, administration of glucagon by the control system was more effective in preventing hypoglycemia. We evaluated the role of plasma insulin and plasma glucagon levels in determining whether glucagon was effective in preventing hypoglycemia.

A bihormonal closed-loop artificial pancreas for type 1 diabetes.

Automated control of blood glucose (BG) concentration is a long-sought goal for type 1 diabetes therapy. We have developed a closed-loop control system that uses frequent measurements of BG concentration along with subcutaneous delivery of both the fast-acting insulin analog lispro and glucagon (to imitate normal physiology) as directed by a computer algorithm. The algorithm responded only to BG concentrations and incorporated a pharmacokinetic model for lispro.

A feasibility study of bihormonal closed-loop blood glucose control using dual subcutaneous infusion of insulin and glucagon in ambulatory diabetic swine.

Background: We sought to test the feasibility and efficacy of bihormonal closed-loop blood glucose (BG) control that utilizes subcutaneous (SC) infusion of insulin and glucagon, a model-predictive control algorithm for determining insulin dosing, and a proportional-derivative control algorithm for determining glucagon dosing.

Methods: Thirteen closed-loop experiments (approximately 7-27 h in length) were conducted in six ambulatory diabetic pigs weighing 26-50 kg. In all experiments, venous BG was sampled through a central line in the vena cava.

Pharmacodynamics and stability of subcutaneously infused glucagon in a type 1 diabetic Swine model in vivo.

Background: The objective of this study was to determine the in vivo pharmacodynamics of glucagon and to test its glycemic effect over days by assessing its time course of activity and potency in a type 1 diabetic swine model.

Methods: Individual experiments were conducted in different pigs using glucagon preparations that were reconstituted on different days and stored at room temperature or near body temperature before usage. All experiments involved a subcutaneous bolus of glucagon to counter impending hypoglycemia induced by an earlier bolus of fast-acting insulin.

Adaptive closed-loop control provides blood-glucose regulation using dual subcutaneous insulin and glucagon infusion in diabetic Swine.

Background: In order to stave off deleterious complications of the disease, the ultimate task for people with diabetes is to maintain their blood glucose in euglycemic range. Despite technological advancements, conventional open-loop therapy often results in prolonged hyperglycemia and episodic hypoglycemia, in addition to necessitating carbohydrate counting, frequent glucose monitoring, and drug administration. The logical conclusion in the evolution of exogenous insulin therapy is to develop an automated closed-loop control system.