Online Classification of Unstructured Free-Living Exercise Sessions in People with Type 1 Diabetes.

Background: Managing exercise in type 1 diabetes is challenging, in part, because different types of exercises can have diverging effects on glycemia. The aim of this work was to develop a classification model that can classify an exercise event (structured or unstructured) as aerobic, interval, or resistance for the purpose of incorporation into an automated insulin delivery (AID) system. Methods: A long short-term memory network model was developed with real-world data from 30-min structured sessions of at-home exercise (aerobic, resistance, or mixed) using triaxial accelerometer, heart rate, and activity duration information. The detection algorithm was used to classify 15 common free-living and unstructured activities and relate each to exercise-associated change in glucose. Results: A total of 1610 structured exercise sessions were used to train, validate, and test the model. The accuracy for the structured exercise sessions in the testing set was 72% for aerobic, 65% for interval, and 77% for resistance. In addition, we tested the classifier on 3328 unstructured sessions. We validated the session-associated change in glucose against the expected change during exercise for each type. Mean and standard deviation of the change in glucose of -20.8 (40.3) mg/dL were achieved for sessions classified as aerobic, -16.2 (39.0) mg/dL for sessions classified as interval, and -11.6 (38.8) mg/dL for sessions classified as resistance. Conclusions: The proposed algorithm reliably identified physical activity associated with expected change in glucose, which could be integrated into an AID system to manage the exercise disturbance in glycemia according to the predicted class.

First Outpatient Clinical Trial of a Full Closed-Loop Artificial Pancreas System in South America.

BACKGROUND: The first two studies of an artificial pancreas (AP) system carried out in Latin America took place in 2016 (phase 1) and 2017 (phase 2). They evaluated a hybrid algorithm from the University of Virginia (UVA) and the automatic regulation of glucose (ARG) algorithm in an inpatient setting using an AP platform developed by the UVA. The ARG algorithm does not require carbohydrate (CHO) counting and does not deliver meal priming insulin boluses. Here, the first outpatient trial of the ARG algorithm using an own AP platform and doubling the duration of previous phases is presented. METHOD: Phase 3 involved the evaluation of the ARG algorithm in five adult participants (n = 5) during 72 hours of closed-loop (CL) and 72 hours of open-loop (OL) control in an outpatient setting. This trial was performed with an own AP and remote monitoring platform developed from open-source resources, called InsuMate. The meals tested ranged its CHO content from 38 to 120 g and included challenging meals like pasta. Also, the participants performed mild exercise (3-5 km walks) daily. The clinical trial is registered in ClinicalTrials.gov with identifier: NCT04793165. RESULTS: The ARG algorithm showed an improvement in the time in hyperglycemia (52.2% [16.3%] OL vs 48.0% [15.4%] CL), time in range (46.9% [15.6%] OL vs 50.9% [14.4%] CL), and mean glucose (188.9 [25.5] mg/dl OL vs 186.2 [24.7] mg/dl CL) compared with the OL therapy. No severe hyperglycemia or hypoglycemia episodes occurred during the trial. The InsuMate platform achieved an average of more than 95% of the time in CL. CONCLUSION: The results obtained demonstrated the feasibility of outpatient full CL regulation of glucose levels involving the ARG algorithm and the InsuMate platform.

A Dual-Hormone Multicontroller for Artificial Pancreas Systems.

Artificial pancreas (AP) algorithms can be divided into single-hormone (SH) and dual-hormone (DH). SH algorithms regulate glycemia using insulin as their control input. On the other hand, DH algorithms also use glucagon to counteract insulin. While SH-AP systems are already commercially available, DH-AP systems are still in an earlier research phase. DH-AP systems have been questioned since the added complexity of glucagon infusion does not always guarantee hypoglycemia prevention and might significantly raise insulin delivery. In this work, a DH multicontroller is proposed based on a SH linear quadratic gaussian (LQG) algorithm with an additional LQG controller to deliver glucagon. This strategy has a switched structure that allows activating one of the following three controllers when necessary: a conservative insulin LQG controller to modulate basal delivery ( K1), an aggressive insulin LQG controller to counteract meals ( K2), or a glucagon LQG controller to avoid imminent hypoglycemia ( K3). Here, an in silico study of the benefits of incorporating controller K3 is carried out. Intra-patient variability and mixed meals are considered. Results indicate that the proposed switched, dual-hormone strategy yields to a reduction in hypoglycemia without increasing hyperglycemia, with no significant rise in insulin delivery.

Automatic glycemic regulation for the pediatric population based on switched control and time-varying IOB constraints: an in silico study.

Artificial pancreas (AP) systems have shown to improve glucose regulation in type 1 diabetes (T1D) patients. However, full closed-loop performance remains a challenge particularly in children and adolescents, since these age groups often present the worst glycemic control. In this work, an algorithm based on switched control and time-varying IOB constraints is presented. The proposed control strategy is evaluated in silico using the FDA-approved UVA/ Padova simulator and its performance contrasted with the previously introduced Automatic Regulation of Glucose (ARG) algorithm in the pediatric population. The effect of unannounced meals is also explored. Results indicate that the proposed strategy achieves lower hypo- and hyperglycemia than the ARG for both announced and unannounced meals. Graphical Abstract Block diagram and illustrative example of insulin and glucose evolution over time for the proposed algorithm (ARGAE).

Artificial Pancreas: Evaluating the ARG Algorithm Without Meal Announcement.

BACKGROUND: Either under standard basal-bolus treatment or hybrid closed-loop control, subjects with type 1 diabetes are required to count carbohydrates (CHOs). However, CHO counting is not only burdensome but also prone to errors. Recently, an artificial pancreas algorithm that does not require premeal insulin boluses-the so-called automatic regulation of glucose (ARG)-was introduced. In its first pilot clinical study, although the exact CHO counting was not required, subjects still needed to announce the meal time and classify the meal size. METHOD: An automatic switching signal generator (SSG) is proposed in this work to remove the manual mealtime announcement from the control strategy. The SSG is based on a Kalman filter and works with continuous glucose monitoring readings only. RESULTS: The ARG algorithm with unannounced meals (ARGum) was tested in silico under the effect of different types of mixed meals and intrapatient variability, and contrasted with the ARG algorithm with announced meals (ARGam). Simulations reveal that, for slow-absorbing meals, the time in the euglycemic range, [70-180] mg/dL, increases using the unannounced strategy (ARGam: 78.1 [68.6-80.2]% (median [IQR]) and ARGum: 87.8 [84.5-90.6]%), while similar results were found with fast-absorbing meals (ARGam: 87.4 [86.0-88.9]% and ARGum: 87.6 [86.1-88.8]%). On the other hand, when intrapatient variability is considered, time in euglycemia is also comparable (ARGam: 81.4 [75.4-83.5]% and ARGum: 80.9 [77.0-85.1]%). CONCLUSION: In silico results indicate that it is feasible to perform an in vivo evaluation of the ARG algorithm with unannounced meals.

Artificial Pancreas: Clinical Study in Latin America Without Premeal Insulin Boluses.

BACKGROUND: Emerging therapies such as closed-loop (CL) glucose control, also known as artificial pancreas (AP) systems, have shown significant improvement in type 1 diabetes mellitus (T1DM) management. However, demanding patient intervention is still required, particularly at meal times. To reduce treatment burden, the automatic regulation of glucose (ARG) algorithm mitigates postprandial glucose excursions without feedforward insulin boluses. This work assesses feasibility of this new strategy in a clinical trial. METHODS: A 36-hour pilot study was performed on five T1DM subjects to validate the ARG algorithm. Subjects wore a subcutaneous continuous glucose monitor (CGM) and an insulin pump. Insulin delivery was solely commanded by the ARG algorithm, without premeal insulin boluses. This was the first clinical trial in Latin America to validate an AP controller. RESULTS: For the total 36-hour period, results were as follows: average time of CGM readings in range 70-250 mg/dl: 88.6%, in range 70-180 mg/dl: 74.7%, <70 mg/dl: 5.8%, and <50 mg/dl: 0.8%. Results improved analyzing the final 15-hour period of this trial. In that case, the time spent in range was 70-250 mg/dl: 94.7%, in range 70-180 mg/dl: 82.6%, <70 mg/dl: 4.1%, and <50 mg/dl: 0.2%. During the last night the time spent in range was 70-250 mg/dl: 95%, in range 70-180 mg/dl: 87.7%, <70 mg/dl: 5.0%, and <50 mg/dl: 0.0%. No severe hypoglycemia occurred. No serious adverse events were reported. CONCLUSIONS: The ARG algorithm was successfully validated in a pilot clinical trial, encouraging further tests with a larger number of patients and in outpatient settings.