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.

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A New Symmetrical Thiazolidinedione Derivative: In Silico Design, Synthesis, and In Vivo Evaluation on a Streptozotocin- Induced Rat Model of Diabetes

Processes ◽

10.3390/pr9081294 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1294

Author(s):

Samuel Álvarez-Almazán ◽

Gabriel Navarrete-Vázquez ◽

Itzia Irene Padilla-Martínez ◽

José Correa-Basurto ◽

Diana Alemán-González-Duhart ◽

...

Keyword(s):

Rat Model ◽

In Silico ◽

Female Rats ◽

Therapeutic Effects ◽

Acute Oral Toxicity ◽

Oral Toxicity ◽

In Vivo Evaluation ◽

Docking Simulations ◽

Ppar Γ

By activating PPAR-γ, thiazolidinediones normalize glucose levels in animal models of type 2 diabetes and in patients with this pathology. The aim of the present study was to analyze 219 new derivatives in silico and select the best for synthesis, to be evaluated for acute oral toxicity in female rats and for control of diabetes-related parameters in a rat model of streptozotocin-induced diabetes. The best compound was chosen based on pharmacokinetic, pharmacodynamic, and toxicological parameters obtained in silico and binding orientation observed by docking simulations on PPAR-γ. Compound 1G was synthesized by a quick and easy Knoevenagel condensation. Acute oral toxicity was found at a dose greater than 2000 mg/Kg. Compound 1G apparently produces therapeutic effects similar to those of pioglitazone, decreasing glycaemia and triglyceride levels in diabetic animals, without liver damage. Moreover, it did not cause a significant weight gain and tended to reduce polydipsia and polyphagia, while diminishing systemic inflammation related to TNF-α and IL-6. It lowered the level of endogenous antioxidant molecules such as reduced glutathione and glutathione reductase. In conclusion, 1G may be a candidate for further testing as an euglycemic agent capable of preventing the complications of diabetes.

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Synthesis and characterization of Chitosan-Catechol conjugates: Development and in vitro, in silico and in vivo evaluation of mucoadhesive pellets of lafutidine

Journal of Bioactive and Compatible Polymers ◽

10.1177/0883911521997849 ◽

2021 ◽

pp. 088391152199784

Author(s):

Loveleen Kaur ◽

Ajay Kumar Thakur ◽

Pradeep Kumar ◽

Inderbir Singh

Keyword(s):

Drug Release ◽

In Silico ◽

Ex Vivo ◽

Strong Interactions ◽

Dissolution Time ◽

Sem Images ◽

In Vivo Evaluation ◽

Release Studies

Present study was aimed to synthesize and characterize Chitosan-Catechol conjugates and to design and develop mucoadhesive pellets loaded with lafutidine. SEM images indicated the presence of fibrous structures responsible for enhanced mucoadhesive potential of Chitosan-Catechol conjugates. Thermodynamic stability and amorphous nature of conjugates was confirmed by DSC and XRD studies respectively. Rheological studies were used to evaluate polymer mucin interactions wherein strong interactions between Chitosan-Catechol conjugate and mucin was observed in comparison to pristine chitosan and mucin. The mucoadhesion potential of Chitosan-Catechol (Cht-C) versus Chitosan (Cht) was assessed in silico using molecular mechanics simulations and the results obtained were compared with the in vitro and ex vivo results. Cht-C/mucin demonstrated much higher energy stabilization (∆E ≈ −65 kcal/mol) as compared to Cht/mucin molecular complex. Lafutidine-loaded pellets were prepared from Chitosan (LPC) and Chitosan-Catechol conjugates (LPCC) and were evaluated for various physical properties viz. flow, circularity, roundness, friability, drug content, particle size and percent mucoadhesion. In vitro drug release studies on LPC and LPCC pellets were performed for computing t50%, t90% and mean dissolution time. The values of release exponent from Korsmeyer-Peppas model was reported to be 0.443 and 0.759 for LPC and LPCC pellets suggesting Fickian and non-Fickian mechanism representing drug release, respectively. In vivo results depicted significant controlled release and enhanced residence of the drug after being released from the chitosan-catechol coated pellets. Chitosan-Catechol conjugates were found to be a promising biooadhesive polymer for the development of various mucoadhesive formulations.

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The UVA/Padova Type 1 Diabetes Simulator Goes From Single Meal to Single Day

Journal of Diabetes Science and Technology ◽

10.1177/1932296818757747 ◽

2018 ◽

Vol 12 (2) ◽

pp. 273-281 ◽

Cited By ~ 41

Author(s):

Roberto Visentin ◽

Enrique Campos-Náñez ◽

Michele Schiavon ◽

Dayu Lv ◽

Martina Vettoretti ◽

...

Keyword(s):

Type 1 Diabetes ◽

In Silico ◽

Artificial Pancreas ◽

Real Life ◽

Glucose Monitoring ◽

Glucose Variability ◽

Self Monitoring ◽

Inhaled Insulin ◽

Single Meal

Background: A new version of the UVA/Padova Type 1 Diabetes (T1D) Simulator is presented which provides a more realistic testing scenario. The upgrades to the previous simulator, which was accepted by the Food and Drug Administration in 2013, are described. Method: Intraday variability of insulin sensitivity (SI) has been modeled, based on clinical T1D data, accounting for both intra- and intersubject variability of daily SI. Thus, time-varying distributions of both subject’s basal insulin infusion and insulin-to-carbohydrate ratio were calculated and made available to the user. A model of “dawn” phenomenon based on clinical T1D data has been also included. Moreover, the model of subcutaneous insulin delivery has been updated with a recently developed model of commercially available fast-acting insulin analogs. Models of both intradermal and inhaled insulin pharmacokinetics have been included. Finally, new models of error affecting continuous glucose monitoring and self-monitoring of blood glucose devices have been added. Results: One hundred in silico adults, adolescent, and children have been generated according to the above modifications. The new simulator reproduces the intraday glucose variability observed in clinical data, also describing the nocturnal glucose increase, and the simulated insulin profiles reflect real life data. Conclusions: The new modifications introduced in the T1D simulator allow to extend its domain of validity from “single-meal” to “single-day” scenarios, thus enabling a more realistic framework for in silico testing of advanced diabetes technologies including glucose sensors, new insulin molecules and artificial pancreas.

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N-pyridin-2-yl benzamide analogues as allosteric activators of glucokinase: Design, synthesis, in vitro,in silico and in vivo evaluation

Chemical Biology & Drug Design ◽

10.1111/cbdd.13423 ◽

2018 ◽

Vol 93 (3) ◽

pp. 364-372 ◽

Cited By ~ 2

Author(s):

Ajmer Singh Grewal ◽

Rajeev Kharb ◽

Deo Nandan Prasad ◽

Jagdeep Singh Dua ◽

Viney Lather

Keyword(s):

In Silico ◽

In Vivo Evaluation ◽

Design Synthesis

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In silico identification of potent inhibitors of alpha-synuclein aggregation and its in vivo evaluation using MPTP induced Parkinson mice model

Biomedicine & Aging Pathology ◽

10.1016/j.biomag.2014.01.002 ◽

2014 ◽

Vol 4 (2) ◽

pp. 147-152 ◽

Cited By ~ 5

Author(s):

Richard L. Jayaraj ◽

Namasivayam Elangovan

Keyword(s):

In Silico ◽

Alpha Synuclein ◽

Mice Model ◽

In Vivo Evaluation ◽

In Silico Identification ◽

Alpha Synuclein Aggregation

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In vitro and in vivo Evaluation of in silico Predicted Pneumococcal UDPG:PP Inhibitors

Frontiers in Microbiology ◽

10.3389/fmicb.2020.01596 ◽

2020 ◽

Vol 11 ◽

Cited By ~ 1

Author(s):

Freya Cools ◽

Dhoha Triki ◽

Nele Geerts ◽

Peter Delputte ◽

Denis Fourches ◽

...

Keyword(s):

In Silico ◽

In Vivo Evaluation

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Design synthesis in silico in vitro and in vivo evaluation of novel l-cysteine derivatives as multi-target-directed ligands for the treatment of neurodegenerative diseases

Beni-Suef University Journal of Basic and Applied Sciences ◽

10.1016/j.bjbas.2018.04.001 ◽

2018 ◽

Vol 7 (4) ◽

pp. 452-460

Author(s):

Vadivel Kannan ◽

Manohar Babu Sitty ◽

Muthusamy Periyannan

Keyword(s):

Neurodegenerative Diseases ◽

In Silico ◽

In Vivo Evaluation ◽

Design Synthesis

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Glucagon sensitivity and clearance in type 1 diabetes: insights from in vivo and in silico experiments

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00236.2015 ◽

2015 ◽

Vol 309 (5) ◽

pp. E474-E486 ◽

Cited By ~ 11

Author(s):

Ling Hinshaw ◽

Ashwini Mallad ◽

Chiara Dalla Man ◽

Rita Basu ◽

Claudio Cobelli ◽

...

Keyword(s):

Type 1 Diabetes ◽

In Silico ◽

Artificial Pancreas ◽

Glucose Production ◽

Endogenous Glucose Production ◽

Action Model ◽

The Difference ◽

Hormone Control

Glucagon use in artificial pancreas for type 1 diabetes (T1D) is being explored for prevention and rescue from hypoglycemia. However, the relationship between glucagon stimulation of endogenous glucose production (EGP) viz., hepatic glucagon sensitivity, and prevailing glucose concentrations has not been examined. To test the hypothesis that glucagon sensitivity is increased at hypoglycemia vs. euglycemia, we studied 29 subjects with T1D randomized to a hypoglycemia or euglycemia clamp. Each subject was studied at three glucagon doses at euglycemia or hypoglycemia, with EGP measured by isotope dilution technique. The peak EGP increments and the integrated EGP response increased with increasing glucagon dose during euglycemia and hypoglycemia. However, the difference in dose response based on glycemia was not significant despite higher catecholamine concentrations in the hypoglycemia group. Knowledge of glucagon's effects on EGP was used to develop an in silico glucagon action model. The model-derived output fitted the obtained data at both euglycemia and hypoglycemia for all glucagon doses tested. Glucagon clearance did not differ between glucagon doses studied in both groups. Therefore, the glucagon controller of a dual hormone control system may not need to adjust glucagon sensitivity, and hence glucagon dosing, based on glucose concentrations during euglycemia and hypoglycemia.

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