Newest diabetes related technologies for pediatric type 1 diabetes and its impact on routine care : a narrative synthesis of the literature

Purpose of Review This review aims to address the actual state of the most advanced diabetes devices, as follows: continuous subcutaneous insulin infusions (CSII), continuous glucose monitoring systems (CGM), hybrid-closed loop (HCL) systems, and “Do-it-yourself” Artifcial Pancreas Systems (DIYAPS) in children, adolescents, and young adults. This review has also the objective to assess the use of telemedicine for diabetes care across three diferent areas: education, social media, and daily care. Recent Findings Recent advances in diabetes technology after integration of CSII with CGM have increased the popularity of this treatment modality in pediatric age and shifted the standard diabetes management in many countries. We found an impressive transition from the use of CSII and/or CGM only to integrative devices with automated delivery systems. Although much has changed over the past 5 years, including a pandemic period that precipitated a broader use of telemedicine in diabetes care, some advances in technology may still be an additional burden of care for providers, patients, and caregivers. The extent of a higher rate of “auto-mode” use in diabetes devices while using the HCL/DIYAPS is essential to reduce the burden of diabetes treatment. Summary More studies including higher-risk populations are needed, and eforts should be taken to ensure proper access to cost-efective advanced technology on diabetes care

A Preventive Medicine Framework for Wearable Abiotic Glucose Detection System

In this work, we present a novel abiotic glucose fuel cell with battery-less remote access. In the presence of a glucose analyte, we characterized the power generation and biosensing capabilities. This system is developed on a flexible substrate in bacterial nanocellulose with gold nanoparticles used as a conductive ink for piezoelectric deposition based printing. The abiotic glucose fuel cell is constructed using colloidal platinum on gold (Au-co-Pt) and a composite of silver oxide nanoparticles and carbon nanotubes as the anodic and cathodic materials. At a concentration of 20 mM glucose, the glucose fuel cell produced a maximum open circuit voltage of 0.57 V and supplied a maximum short circuit current density of 0.581 mA/cm2 with a peak power density of 0.087 mW/cm2 . The system was characterized by testing its performance using electrochemical techniques like linear sweep voltammetry, cyclic voltammetry, chronoamperometry in the presence of various glucose level at the physiological temperatures. An open circuit voltage (Voc) of 0.43 V, short circuit current density (Isc) of 0.405 mA/cm2 , and maximum power density (Pmax) of 0.055 mW/cm2 at 0.23 V were achieved in the presence of 5 mM physiologic glucose. The results indicate that glucose fuel cells can be employed for the development of a self-powered glucose sensor. The glucose monitoring device demonstrated sensitivity of 1.87 uA/mMcm2 and a linear dynamic range of 1 mM to 45 mM with a correlation coefficient of 0.989 when utilized as a self-powered glucose sensor. For wireless communication, the incoming voltage from the abiotic fuel cell was fed to a low power microcontroller that enables battery less communication using NFC technology. The voltage translates to the NFC module as the digital signals, which are displayed on a custom-built android application. The digital signals are converted to respective glucose concentration using a correlation algorithm that allows data to be processed and recorded for further analysis. The android application is designed to record the time, date stamp, and other independent features (e.g. age, height, weight) with the glucose measurement to allow the end-user to keep track of their glucose levels regularly. Analytics based on in-vitro testing were conducted to build a machine learning model that enables future glucose prediction for 15, 30 or 60 minutes

Low-power Wearable Healthcare Sensors

Advances in technology have produced a range of on-body sensors and smartwatches that can be used to monitor a wearer’s health with the objective to keep the user healthy. However, the real potential of such devices not only lies in monitoring but also in interactive communication with expert-system-based cloud services to offer personalized and real-time healthcare advice that will enable the user to manage their health and, over time, to reduce expensive hospital admissions. To meet this goal, the research challenges for the next generation of wearable healthcare devices include the need to offer a wide range of sensing, computing, communication, and human–computer interaction methods, all within a tiny device with limited resources and electrical power. This Special Issue presents a collection of six papers on a wide range of research developments that highlight the specific challenges in creating the next generation of low-power wearable healthcare sensors

Standardization in the field of composites

The modern era of composite materials begins at the end of the 19th century with the production of the first polymer–based artificial resins. Since then, the types and technologies of composite materials have been continuously developed and improved, until today. Their use in modern industry is progressively growing. That is why orderliness and regularity are necessary for the development, production, meeting of market requirements, exploitation and recycling of these materials. It can only be achieved through standards and standardization. Within the technical committee TC 61 of the International Organization for Standardization – ISO, the subcommittee ISO/TC 61/SC 13, which deals with composites and reinforcing fibres, operates. The American Society for Testing and Materials – ASTM International also publishes international standards. The D30 committee for composite materials operates within this organization. ISO/TC 61/SC 13 has existed since 1985, and ASTM/D30 since 1964. In this paper, an analysis of the number, types and dynamics of the publication of standards in the field of composites and related fields was carried out. Based on the analysis carried out, it was concluded that a large number of significant standards have been published, that the number of standards is increasing following the development of new composite materials, as well as that further expansion of the concept of standardization in the field of composites can be expected. The results shown here are the result of research supported by COST action CA21155 – Advanced Composites under HIgh STRAin RaTEs Loading: a route to certification–by–analysis (HISTRATE)

Impact of Sensing and Actuation Characteristics on Artificial Pancreas Design

Type 1 diabetes mellitus (T1DM) is a chronic disease characterized by the body’s inability to produce insulin, leading to chronically high blood glucose (BG) concentrations. T1DM is treated by frequent self-administration of insulin based on BG measurements; however, there is a fine line between too little and too much insulin, and an overdose can lead to a dangerous drop in BG. The artificial pancreas (AP), consisting of a glucose sensor, an insulin pump, and a feedback control algorithm, will replace self-treatment by automatically calculating and delivering insulin dosages based on continuous glucose measurements. Many iterations of the AP utilize commercially available subcutaneous (SC) insulin pumps and glucose sensors, but these devices introduce physiological limitations that make control difficult. In this work, we present a clinical evaluation of an AP that uses SC devices, as well as an investigation of the intraperitoneal (IP) space as an alternative site for insulin delivery and glucose sensing to improve AP performance. Our results show that glucose sensors placed in the IP space have a lower time constant than SC sensors, allowing the controller to respond more quickly to BG disturbances. Similarly, insulin delivered through the IP space has faster pharmacokinetic and pharmacodynamic characteristics than SC insulin. Based on models of the sensing and actuation dynamics, a proportional-integral-derivative control algorithm with anti-reset windup protection was designed for the IP-IP route and evaluated on 10 simulated T1DM subjects. Using the IP-IP route led to a more robust controller that provided excellent control during the simulation studies. Our results support the development of a fully implantable AP that will operate within the IP space to safely and effectively control BG levels

Report from IPITA-TTS opinion leaders meeting on the future of β-cell replacement

Peer reviewe

Intelligent Remote Monitoring and Management system for Type1 Diabetes

The work presented in this thesis focuses on developing a telemedicine system for better management of type1 diabetes in children and teenagers. The research and development of the system is motivated by the inadequate communication in the current system of management of the disease, which results in non-compliance of patients following the regimen. This non-compliance generally results in uncontrolled blood glucose levels, which can result in hypoglycaemia, hyperglycaemia and later life health complications. This further results in an increase in health care costs. In this context, the thesis presents a novel end-to-end, low cost telemedicine system, WithCare+, developed in close collaboration between the University of Sheffield (Electronics & Electrical Engineering) and Sheffield Children’s Hospital. The system was developed to address the challenges of implementing modern telemedicine in type 1 diabetic care with particular relevance to National Health Service children’s clinics in the United Kingdom, by adopting a holistic care driven approach (involving all stakeholders) based on specific key enabler technologies such as low cost and reconfigurable design. However, one of the major issues with current telemedicine system is non-compliance of the patients due to invasive procedure of the glucose measurement which could be clearly addressed by non-invasive method of glucose measurement. Hence, the thesis also makes a contribution towards non-invasive glucose measurement using Near Infrared spectroscopy in terms of addressing the calibration challenge; two methods are proposed to improve the calibration of the Near Infrared instrument. The first method combines locally weighted regression and partial least square regression and the second method combines digital band pass filtering with support vector regression. The efficacy of the proposed methods is validated in experiments carried out in a non-controlled environment and the results obtained demonstrate that the proposed methods improved the performance of the calibration model in comparison to traditional calibration techniques such as Principal Component Regression and Partial Least Squares regression

Multicellular Systems Biology of Development

Embryonic development depends on the precise coordination of cell fate specification, patterning and morphogenesis. Although great strides have been made in the molecular understanding of each of these processes, how their interplay governs the formation of complex tissues remains poorly understood. New techniques for experimental manipulation and image quantification enable the study of development in unprecedented detail, resulting in new hypotheses on the interactions between known components. By expressing these hypotheses in terms of rules and equations, computational modeling and simulation allows one to test their consistency against experimental data. However, new computational methods are required to represent and integrate the network of interactions between gene regulation, signaling and biomechanics that extend over the molecular, cellular and tissue scales. In this thesis, I present a framework that facilitates computational modeling of multiscale multicellular systems and apply it to investigate pancreatic development and the formation of vascular networks. This framework is based on the integration of discrete cell-based models with continuous models for intracellular regulation and intercellular signaling. Specifically, gene regulatory networks are represented by differential equations to analyze cell fate regulation; interactions and distributions of signaling molecules are modeled by reaction-diffusion systems to study pattern formation; and cell-cell interactions are represented in cell-based models to investigate morphogenetic processes. A cell-centered approach is adopted that facilitates the integration of processes across the scales and simultaneously constrains model complexity. The computational methods that are required for this modeling framework have been implemented in the software platform Morpheus. This modeling and simulation environment enables the development, execution and analysis of multi-scale models of multicellular systems. These models are represented in a new domain-specific markup language that separates the biological model from the computational methods and facilitates model storage and exchange. Together with a user-friendly graphical interface, Morpheus enables computational modeling of complex developmental processes without programming and thereby widens its accessibility for biologists. To demonstrate the applicability of the framework to problems in developmental biology, two case studies are presented that address different aspects of the interplay between cell fate specification, patterning and morphogenesis. In the first, I focus on the interplay between cell fate stability and intercellular signaling. Specifically, two studies are presented that investigate how mechanisms of cell-cell communication affect cell fate regulation and spatial patterning in the pancreatic epithelium. Using bifurcation analysis and simulations of spatially coupled differential equations, it is shown that intercellular communication results in a multistability of gene expression states that can explain the scattered spatial distribution and low cell type ratio of nascent islet cells. Moreover, model analysis shows that disruption of intercellular communication induces a transition between gene expression states that can explain observations of in vitro transdifferentiation from adult acinar cells into new islet cells. These results emphasize the role of the multicellular context in cell fate regulation during development and may be used to optimize protocols for cellular reprogramming. The second case study focuses on the feedback between patterning and morphogenesis in the context of the formation of vascular networks. Integrating a cell-based model of endothelial chemotaxis with a reaction-diffusion model representing signaling molecules and extracellular matrix, it is shown that vascular network patterns with realistic morphometry can arise when signaling factors are retained by cell-modified matrix molecules. Through the validation of this model using in vitro assays, quantitative estimates are obtained for kinetic parameters that, when used in quantitative model simulations, confirm the formation of vascular networks under measured biophysical conditions. These results demonstrate the key role of the extracellular matrix in providing spatial guidance cues, a fact that may be exploited to enhance vascularization of engineered tissues. Together, the modeling framework, software platform and case studies presented in this thesis demonstrate how cell-centered computational modeling of multi-scale and multicellular systems provide powerful tools to help disentangle the complex interplay between cell fate specification, patterning and morphogenesis during embryonic development