Integrating metabolic expenditure information from wearable fitness sensors into an AI-augmented automated insulin delivery system: a randomised clinical trial.

Background: Exercise can rapidly drop glucose in people with type 1 diabetes. Ubiquitous wearable fitness sensors are not integrated into automated insulin delivery (AID) systems. We hypothesised that an AID can automate insulin adjustments using real-time wearable fitness data to reduce hypoglycaemia during exercise and free-living conditions compared with an AID not automating use of fitness data.

Enabling fully automated insulin delivery through meal detection and size estimation using Artificial Intelligence.

We present a robust insulin delivery system that includes automated meal detection and carbohydrate content estimation using machine learning for meal insulin dosing called robust artificial pancreas (RAP). We conducted a randomized, single-center crossover trial to compare postprandial glucose control in the four hours following unannounced meals using a hybrid model predictive control (MPC) algorithm and the RAP system. The RAP system includes a neural network model to automatically detect meals and deliver a recommended meal insulin dose.

Assessment of a Decision Support System for Adults with Type 1 Diabetes on Multiple Daily Insulin Injections.

DailyDose is a decision support system designed to provide real-time dosing advice and weekly insulin dose adjustments for adults living with type 1 diabetes using multiple daily insulin injections. Twenty-five adults were enrolled in this single-arm study. All participants used Dexcom G6 for continuous glucose monitoring, InPen for short-acting insulin doses, and Clipsulin to track long-acting insulin doses.

Separating insulin-mediated and non-insulin-mediated glucose uptake during and after aerobic exercise in type 1 diabetes.

Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal).

Accuracy of the Dexcom G6 Glucose Sensor during Aerobic, Resistance, and Interval Exercise in Adults with Type 1 Diabetes.

The accuracy of continuous glucose monitoring (CGM) sensors may be significantly impacted by exercise. We evaluated the impact of three different types of exercise on the accuracy of the Dexcom G6 sensor. Twenty-four adults with type 1 diabetes on multiple daily injections wore a G6 sensor.

Dual-Hormone Closed-Loop System Using a Liquid Stable Glucagon Formulation Versus Insulin-Only Closed-Loop System Compared With a Predictive Low Glucose Suspend System: An Open-Label, Outpatient, Single-Center, Crossover, Randomized Controlled Trial.

Objective: To assess the efficacy and feasibility of a dual-hormone (DH) closed-loop system with insulin and a novel liquid stable glucagon formulation compared with an insulin-only closed-loop system and a predictive low glucose suspend (PLGS) system.

Research Design And Methods: In a 76-h, randomized, crossover, outpatient study, 23 participants with type 1 diabetes used three modes of the Oregon Artificial Pancreas system: ) dual-hormone (DH) closed-loop control, ) insulin-only single-hormone (SH) closed-loop control, and ) PLGS system. The primary end point was percentage time in hypoglycemia (<70 mg/dL) from the start of in-clinic aerobic exercise (45 min at 60% VO) to 4 h after.

Measuring glucose at the site of insulin delivery with a redox-mediated sensor.

Automated insulin delivery systems for people with type 1 diabetes rely on an accurate subcutaneous glucose sensor and an infusion cannula that delivers insulin in response to measured glucose. Integrating the sensor with the infusion cannula would provide substantial benefit by reducing the number of devices inserted into subcutaneous tissue. We describe the sensor chemistry and a calibration algorithm to minimize impact of insulin delivery artifacts in a new glucose sensing cannula.

An artificial intelligence decision support system for the management of type 1 diabetes.

Type 1 diabetes (T1D) is characterized by pancreatic beta cell dysfunction and insulin depletion. Over 40% of people with T1D manage their glucose through multiple injections of long-acting basal and short-acting bolus insulin, so-called multiple daily injections (MDI). Errors in dosing can lead to life-threatening hypoglycaemia events (<70 mg dl) and hyperglycaemia (>180 mg dl), increasing the risk of retinopathy, neuropathy, and nephropathy.

Randomized Outpatient Trial of Single- and Dual-Hormone Closed-Loop Systems That Adapt to Exercise Using Wearable Sensors.

Objective: Automated insulin delivery is the new standard for type 1 diabetes, but exercise-related hypoglycemia remains a challenge. Our aim was to determine whether a dual-hormone closed-loop system using wearable sensors to detect exercise and adjust dosing to reduce exercise-related hypoglycemia would outperform other forms of closed-loop and open-loop therapy.

Research Design And Methods: Participants underwent four arms in randomized order: dual-hormone, single-hormone, predictive low glucose suspend, and continuation of current care over 4 outpatient days.

The effect of exercise on sleep in adults with type 1 diabetes.

The aim of this pilot study was to investigate the effect of exercise on sleep and nocturnal hypoglycaemia in adults with type 1 diabetes (T1D). In a 3-week crossover trial, 10 adults with T1D were randomized to perform aerobic, resistance or no exercise. During each exercise week, participants completed 2 separate 45-minutes exercise sessions at an academic medical center.

Comparative Pharmacokinetic/Pharmacodynamic Study of Liquid Stable Glucagon Versus Lyophilized Glucagon in Type 1 Diabetes Subjects.

Background: There is currently no stable liquid form of glucagon commercially available. The aim of this study is to assess the speed of absorption and onset of action of G-Pump™ glucagon at 3 doses as compared to GlucaGen®, all delivered subcutaneously via an OmniPod®.

Methods: Nineteen adult subjects with type 1 diabetes participated in this Phase 2, randomized, double-blind, cross-over, pharmacokinetic/pharmacodynamic study.

Incorporating an Exercise Detection, Grading, and Hormone Dosing Algorithm Into the Artificial Pancreas Using Accelerometry and Heart Rate.

In this article, we present several important contributions necessary for enabling an artificial endocrine pancreas (AP) system to better respond to exercise events. First, we show how exercise can be automatically detected using body-worn accelerometer and heart rate sensors. During a 22 hour overnight inpatient study, 13 subjects with type 1 diabetes wearing a Zephyr accelerometer and heart rate monitor underwent 45 minutes of mild aerobic treadmill exercise while controlling their glucose levels using sensor-augmented pump therapy.

Effect of Repeated Glucagon Doses on Hepatic Glycogen in Type 1 Diabetes: Implications for a Bihormonal Closed-Loop System.

Objective: To evaluate subjects with type 1 diabetes for hepatic glycogen depletion after repeated doses of glucagon, simulating delivery in a bihormonal closed-loop system.

Research Design And Methods: Eleven adult subjects with type 1 diabetes participated. Subjects underwent estimation of hepatic glycogen using (13)C MRS.

Quantification of the glycemic response to microdoses of subcutaneous glucagon at varying insulin levels.

Objective: Glucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia. However, high insulin concentration lowers the hyperglycemic effect of glucagon, and small doses of glucagon in this setting are ineffective. There are no studies clearly defining the relationship between insulin levels, subcutaneous glucagon, and blood glucose.

Automated control of an adaptive bihormonal, dual-sensor artificial pancreas and evaluation during inpatient studies.

Automated control of blood glucose in patients with type-1 diabetes has not yet been fully implemented. The aim of this study was to design and clinically evaluate a system that integrates a control algorithm with off-the-shelf subcutaneous sensors and pumps to automate the delivery of the hormones glucagon and insulin in response to continuous glucose sensor measurements. The automated component of the system runs an adaptive proportional derivative control algorithm which determines hormone delivery rates based on the sensed glucose measurements and the meal announcements by the patient.

Discomfort from an alkaline formulation delivered subcutaneously in humans: albumin at pH 7 versus pH 10.

Background And Objective: There is a paucity of data regarding tolerability of alkaline drugs administered subcutaneously. The aim of this study was to assess the tolerability of alkaline preparations of human albumin delivered subcutaneously to healthy humans.

Methods: We compared the tolerability of neutral versus alkaline (pH 10) formulations of human albumin in ten volunteers.

Development of a fully automated closed loop artificial pancreas control system with dual pump delivery of insulin and glucagon.

Patients with diabetes have difficulty controlling their blood sugar and suffer from acute effects of hypoglycemia and long-term effects of hyperglycemia, which include disease of the eyes, kidneys and nerves/feet. In this paper, we describe a new system that is used to automatically control blood sugar in people with diabetes through the fully automated measurement of blood glucose levels and the delivery of insulin and glucagon via the subcutaneous route. When a patient's blood sugar goes too high, insulin is given to the patient to bring his/her blood sugar back to a normal level.

A controlled study of the effectiveness of an adaptive closed-loop algorithm to minimize corticosteroid-induced stress hyperglycemia in type 1 diabetes.

To be effective in type 1 diabetes, algorithms must be able to limit hyperglycemic excursions resulting from medical and emotional stress. We tested an algorithm that estimates insulin sensitivity at regular intervals and continually adjusts gain factors of a fading memory proportional-derivative (FMPD) algorithm. In order to assess whether the algorithm could appropriately adapt and limit the degree of hyperglycemia, we administered oral hydrocortisone repeatedly to create insulin resistance.

Pathophysiologically relevant levels of hydrogen peroxide induce glutamate-independent neurodegeneration that involves activation of transient receptor potential melastatin 7 channels.

Stroke/brain ischemia is a leading cause of death and long-term disabilities. Increased oxidative stress plays an important role in the pathology of brain ischemia. Hydrogen peroxide (H(2)O(2)) is a major oxidant known to cause neuronal injury; however, the detailed mechanism remains unclear.

Acid-sensing ion channels in acidosis-induced injury of human brain neurons.

Acidosis is a common feature of the human brain during ischemic stroke and is known to cause neuronal injury. However, the mechanism underlying acidosis-mediated injury of the human brain remains elusive. We show that a decrease in the extracellular pH evoked inward currents characteristic of acid-sensing ion channels (ASICs) and increased intracellular Ca(2+) in cultured human cortical neurons.

Activation of acid-sensing ion channel 1a (ASIC1a) by surface trafficking.

Acid-sensing ion channels (ASICs) are voltage-independent Na(+) channels activated by extracellular protons. ASIC1a is expressed in neurons in mammalian brain and is implicated in long term potentiation of synaptic transmission that contributes to learning and memory. In ischemic brain injury, however, activation of this Ca(2+)-permeable channel plays a critical role in acidosis-mediated, glutamate-independent, Ca(2+) toxicity.

Zinc-induced neurotoxicity mediated by transient receptor potential melastatin 7 channels.

Transient receptor potential melastatin 7 (TRPM7) channels are novel Ca(2+)-permeable non-selective cation channels ubiquitously expressed. Activation of TRPM7 channels has been shown to be involved in cellular Mg(2+) homeostasis, diseases caused by abnormal magnesium absorption, and in Ca(2+)-mediated neuronal injury under ischemic conditions. Here we show strong evidence suggesting that TRPM7 channels also play an important role in cellular Zn(2+) homeostasis and in Zn(2+)-mediated neuronal injury.