bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrochemical Sensor Array for Glucose Monitoring Fabricated by Rapid Immobilization of Active Glucose Oxidase within Photochemically Polymerized Hydrogels
Authors: Mugweru Amos , Clark Becky L. , Pishko Michael V. 
Published: January 2014

Background: Currently, monitoring blood glucose levels for diabetic patients is invasive and painful, involving pricking the finger to obtain a blood sample three to four times daily. The need for frequent tests and pain involved with testing leads to poor compliance. In order to raise compliance, we propose to create an implantable electrochemical sensor array that would monitor glucose levels continuously. Methods: Glucose sensor arrays were fabricated on gold electrodes on flexible polyimide sheets by photopolymerization of the biocompatible polymer poly(ethylene glycol) diacrylate (PEG-DA) to develop hydrogels and encapsulate the sensing elements. Using conventional silicon fabrication methods, arrays of five gold microdisk electrodes were fabricated using lift-off photolithography and sputtering techniques. A redox polymer was then attached electrostatically to the electrode, and glucose oxidase was entrapped inside the hydrogel on the array of electrodes by ultraviolet-initiated photopolymerization of PEG-DA. Results: When the array of fabricated sensors was sampled together the elements behaved like one large electrode with peak current equivalent to the sum of individual array elements. The enzyme, glucose oxidase, catalyzed the oxidation of glucose and then exchanged electrons with the redox polymer in the hydrogel. The entrapped glucose oxidase was found to respond linearly to increasing glucose concentrations (0–360 mg/dl), as determined using cyclic voltammetry. Conclusion: The fabricated microarray sensors were individually addressable and showed no cross talk between adjacent array elements as assessed using cyclic voltammetry. We have fabricated an array of glucose sensors on flexible polyimide sheets that exhibits the desired linear response in the biological range.
On-Chip Microdialysis System with Flow-Through Glucose Sensing Capabilities
Authors: Hsieh Yi-Cheng , Zahn Jeffrey D. 
Published: January 2014

Background: Microdialysis is a sampling technique based on controlling the mass transfer rate of different-sized molecules across a semipermeable membrane. Because the dialysis process has minimal effects on the surrounding fluid, it is viewed as a tool for continuous monitoring of human metabolites. In diabetes treatment, microdialysis probes have been used as sampling systems coupled to a glucose biosensor but may struggle to obtain high recoveries of analytes, as the sampling housing, probes, and glucose sensors are fabricated as separate pieces and then assembled, resulting in a large dead volume, which limits sensing frequency. An in situ combination of a miniaturized microdialysis probe with an integrated glucose sensor could help solve some of these problems. Method: The system was fabricated by bonding a 6-μm-thick polycarbonate track-etch membrane with 100-nm-diameter pores onto microfluidic channels with the electrochemical glucose sensing electrodes patterned within the microchannels. Results: In vitro experiments demonstrating glucose microdialysis with continuous sensing were conducted. The permeability of glucose to the polycarbonate membrane with a 100-nm-diameter pore size was obtained to be 5.44 μm/s. Glucose recovery of 99% was observed using this microdialysis system at a perfusion flow rate of 0.5 μl/min. Experiments monitoring fluctuating glucose concentrations in the time domain at 99% recovery were also performed. The lag time was measured to be 210 seconds with 45 seconds contributed by mass transfer limitations and the rest from dead volume within the experimental setup. Conclusion: The electrochemical sensing component was able to continuously track concentration changes in the reservoir. This system is expected to have the proper sensitivity to track physiologically relevant concentration changes of glucose with a lag time of less than 1 minute and minimal amplitude reduction for continuous glucose monitoring for diabetes treatment.
Fiber-Coupled Fluorescence Affinity Sensor for 3-Day in Vivo Glucose Sensing
Authors: Ballerstadt Ralph , Evans Colton , Gowda Ashok , McNichols Roger 
Published: January 2014

Background: To evaluate the feasibility of an implantable fiber-coupled fluorescence affinity sensor (FAS) for glucose monitoring in humans, we studied the acute and chronic in vivo performance in hairless rats and pigs. Methods: The implantable fiber-coupled FAS was constructed by filling a dialysis chamber made of a regenerated cellulose membrane mounted to the distal tip of an optical fiber with fluorescent chemistry based on concanavalin A. Blood sugar changes in animals were induced by injections of insulin and dextrose. Determination of interstitial glucose concentrations in skin tissue was facilitated by measuring the fluorescence response of the FAS. Results: The acute in vivo response of the fiber-coupled FAS exhibited good correlation coefficients (>0.77) with blood sugar changes and minimal lag times (2–10 min) after 2 hours of sensor implantation. Equilibrium of the sensor signal with interstitial fluid was required less than 60 min after implantation. For both rats and pigs, chronic response of the FAS to blood sugar modulations measured during the third day of implantation successfully demonstrated proof-of-concept for short-term glucose monitoring. A slight decrease in sensitivity after 3 days in the small animal model was assumed to be caused by excessive mechanical forces on the implanted device because of high animal motility. Conclusions: Overall, the chronic in vivo performance of the FAS in two different animal models over 3 days was clinically acceptable and comparable to other continuous glucose monitoring platforms. The major benefit of the FAS is the absence of “autodestructive” side products and any device-related warm-up time after sensor reconnection.
Combined Insulin Pump Therapy with Real-Time Continuous Glucose Monitoring Significantly Improves Glycemic Control Compared to Multiple Daily Injection Therapy in Pump Naïve Patients with Type 1 Diabetes; Single Center Pilot Study Experience
Authors: Lee Scott W. , Sweeney Tom , Clausen Debbie , Kolbach Celia , Hassen Allen , Firek Anthony , Brinegar Charles , Petrofsky Jerrold 
Published: January 2014

Objectives: This study assessed the safety and clinical effectiveness of the training protocol for initiating insulin pump therapy with real-time continuous glucose monitoring (MiniMed Paradigm REAL-Time System) in a stepwise approach on pump naive subjects with type 1 diabetes compared to a control group who remained on multiple daily injection (MDI) therapy. Methods: This was a 15-week treat-to-target pilot study of 16 adult subjects (n = 50% male, age 45.9 ± 16 years) with type 1 diabetes (duration of diabetes 21.9 ± 11 years) on MDI therapy with hemoglobin A1c levels at or above 7.5% at baseline. Subjects were randomized to either the study arm (using a combined insulin pump and real-time continuous glucose monitoring system) or the control arm [which continued on MDI therapy with self-monitored blood glucose (SMBG) only]. All subjects dosed insulin according to results of SMBG by finger stick and uploaded data into the CareLink data management software. Results: Significant improvements in glycemic control were observed from baseline in both study groups—study arm: pre-A1c 9.45 ± 0.55 and post-A1c 7.4 ± 0.66 ( p = 0.00037); control arm: pre-A1c 8.58 ± 1.30 and post-A1c 7.5 ±1.01 ( p = 0.04). Both arms had no incidence of severe hypoglycemia. Conclusion: In this pilot study, the Paradigm REAL-Time System was initiated safely and effectively in type 1 diabetes patients who were pump naïve using a stepwise educational protocol.
Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator
Authors: Lehmann Eldon D. , Tarín Cristina , Bondia Jorge , Teufel Edgar , Deutsch Tibor 
Published: January 2014

Introduction: AIDA v4 is an interactive educational diabetes simulator that has been made available, for over a decade, without charge via the Internet. The software is currently freely accessible at http://www.2aida.org . This report sets out a collaborative development plan to enhance the program with a new model of subcutaneous insulin absorption, which permits the simulation of rapidly acting and very long-acting insulin analogues, as well as insulin injection doses larger than 40 units. Methods: A novel, generic, physiological subcutaneous insulin absorption model is overviewed and a methodology is proposed by which this can be substituted in place of the previously adopted insulin absorption model utilized within AIDA v4.3a. Apart from this substitution it is proposed to retain the existing model of the glucoregulatory system currently used in AIDA v4.3a. Results: Initial simulation results based on bench testing of this approach using MATLAB are presented for the exogenous insulin flow profile ( Iex) following subcutaneous injections of a rapidly acting insulin analogue, a short-acting (regular) insulin preparation, intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue. Discussion It is proposed to implement this collaborative development plan—first by bench testing the approach in MATLAB and then by integrating the generic subcutaneous insulin absorption Iex model into the AIDA simulator in Pascal. The aim is to provide enhanced functionality and educational simulations of regimens utilizing novel insulin analogues, as well as injections larger than 40 units of insulin.
A Telemedicine System That Includes a Personal Assistant Improves Glycemic Control in Pump-Treated Patients with Type 1 Diabetes
Authors: Rigla Mercedes , Hernando M. Elena , Gómez Enrique J. , Brugués Eulalia , García-Sáez Gema , Torralba Verónica , Prados Agustina , Erdozain Luisa , Vilaverde Joana , de Leiva Alberto 
Published: January 2014

Background: The DIABTel system, a Web-based telemedicine application, integrates a whole communication system (glucometer, insulin pump, wireless hand-held assistant) for medical remote advice. We sought to evaluate, in terms of glycemic control, the DIABTel system in a randomized crossover clinical study. Methods: Ten patients with type 1 diabetes [5 women, age 40.6 (21–62) years, diabetes duration 14.7 (3–52) years] were included. During the 4-week active phase, data sent by patients were analyzed by the physician and modifications of the basal rate and bolus were advised in the following 24 hours. During the control phase, patients sent glucose data without any feedback from the medical center. Results: The mean numbers of daily glucose values and bolus sent by patients during the active period were 4.46 ± 0.91 and 4.58 ± 0.89, respectively. The personal digital assistant functionalities used more frequently by patients were (times per week) data visualization (8.1 ± 6.8), data download from the insulin pump (6.8 ± 3.3), and synchronization with the telemedicine server (8.5 ± 4.9). After the experimental phase, serum fructosamine decreased significantly (393 ± 32 vs 366 ± 25 μmol/liter; p < 0.05) and hemoglobin A1c (HbA1c) tended to decrease (8.0 ± 0.6 vs 7.78 ± 0.6; p = 0.073), whereas no changes were observed during the control phase. The number of treatment modifications proposed and performed by the patients correlated with the change observed in HbA1c during the active phase (r = −0.729, p = 0.017). Conclusions: The DIABTel system, a telemedicine system that includes a wireless personal assistant for remote treatment advising, allows better glycemic control in pump-treated patients with type 1 diabetes. To our knowledge, this is the first study that demonstrates improved glycemic control with the use of a telemedicine system that incorporates insulin delivery data.
Performance of Electronic Diaries in Diabetes Clinical Trials Measured through Overall Satisfaction of Site Coordinators
Authors: Jhaveri Mehul , Lee Elizabeth 
Published: January 2014

Background: Clinical trials are increasingly being designed to collect data directly from patients through the use of paper diaries or electronic diaries (e-diaries). E-diaries can be advantageous over paper diaries, but actual benefits may depend on the particular features of a given e-diary. The objective of this study was to determine which e-diary system features are most important to consider when selecting such a tool. Methods: A 42-question survey was distributed to 295 site coordinators participating in four diabetes clinical trials, using e-diary systems provided by three different vendors. The survey gathered information about the site coordinators' experience with the e-diary system used. Analyses included a comparison of global satisfaction rating scores and individual survey item responses among the different e-diaries utilized and correlation of individual survey items with the global satisfaction rating for each system. Results: The survey was completed by 131 site coordinators (44% response rate). Mean global satisfaction rating scores varied from 3.4 to 7.2 ( p < 0.0001). Individual survey items such as technical problems that cannot be resolved easily, the ability of the help line to fully address problems, and organization and user-friendliness of the e-diary's data management Web site were most closely correlated with the global satisfaction rating. The site coordinators' prior e-diary experience and years of job experience did not significantly correlate with the global satisfaction rating. Conclusions: This survey highlights features of e-diaries for sponsors to consider in clinical trials, including the importance of minimizing technical problems, assessing vendors' help line capabilities, and choosing an e-diary system with an efficient and user-friendly data-management Web site.
Quantitation of Humalog Insulin by Reversed-Phase High-Performance Liquid Chromatography
Authors: Munsick Carey , Murray Robert , Dziubla Tom , Lowman Anthony M. , Joseph Jeffrey I. , Torjman Marc C. 
Published: January 2014

Introduction: The methodology for in vitro testing of insulin delivery systems for long-term infusion of lispro insulin requires insulin flow studies over time, with the measurement of lispro concentrations in wells or other laboratory fluid collection systems. We postulated that the efficiency of the insulin assay could be improved if the insulin collected in the wells could be measured without having to perform dilutions of insulin samples. The manufacturer's method for the identification of Humalog® insulin by high-performance liquid chromatography (HPLC) does not provide a detailed method for the quantitation of the clinical formulation. No reports could be found in the literature describing a method to quantitate lispro insulin's entire concentration range, nor could we find detailed information on pH effects. The purpose of this study was to investigate the use of a reversed-phase HPLC method to quantitate Humalog insulin at three levels of pH. Methods: Serial dilutions of Humalog insulin stock solution were prepared at pH levels of 2.6 and 7.4 (concentrations 0.20–100 IU/ml) to construct calibration curves. Samples were also prepared at lower concentrations (0.2315.0 IU/ml) at pH levels of 4.0 and 7.4. Areas under curve data were plotted against known concentrations, and the limit of quantitation and precision of the assay were determined. Results: Calibration curves for the 0.20–100 IU/ml concentration (pH 7.4 and 2.6) revealed no significant differences ( p < 0.01) between those curves. pH and concentration did not have an effect on the overall precision of the method. Linearity was not conserved past the 15-IU/ml concentration. Coefficient of variation (CV) values were generally <15% except at the lower concentrations where the largest CVs were observed. Mean known concentrations plotted on a logarithmic scale demonstrated linearity from 12.5 to 100 IU/ml. Conclusions: Humalog insulin clinical formulation can be quantitated over the entire concentration range by a reversed-phase HPLC method using nonlinear regression analysis. The method is reproducible at lower (<15 IU/ml) and higher insulin concentrations. Linear regression analysis may be used when the concentrations of interest are in the 0- to 15-IU range. Preparation of insulin solutions at pH 2.6, 4.0, and 7.4 did not significantly affect the reproducibility of the assay.
Putative Delays in Interstitial Fluid (ISF) Glucose Kinetics Can Be Attributed to the Glucose Sensing Systems Used to Measure Them Rather than the Delay in ISF Glucose Itself
Authors: Voskanyan Gayane , Keenan D. Barry , Mastrototaro John J. , Steil Garry M. 
Published: January 2014

Background: Since the advent of subcutaneous glucose sensors, there has been intense focus on characterizing the delay in the interstitial fluid (ISF) glucose response and the effect of insulin to alter the plasma-to-ISF glucose gradient. The Medtronic MiniMed continuous glucose monitoring system (CGMS) has often been used for this purpose; however, many of the studies have used experimental conditions that fall outside its intended use, for example, studies that have assessed the delay during rapid glucose excursions brought about by intravenous infusion of glucose or insulin. Under these conditions, it is possible that the rate of glucose change may exceed that allowed by CGMS filtering routines. If so, the estimated delay may be because of the filter rather than the ISF. Also, sensor characteristics, such as nonspecific offset current or stability, may have been inadvertently attributed to changes in the plasma-to-ISF gradient. The potential for these issues to have confounded the understanding of ISF glucose delay and gradient is investigated. Methods: An in vitro preparation in which no delay or gradient exists between sensor and measurement solution was used to recreate a rapidly changing glucose profile from a previously published in vivo study. The CGMS system (N = 6 sensors) was then used to estimate any artifactual delay and gradient introduced by the system per se. Results: One-point calibration resulted in an apparent change in gradient as glucose was lowered from ∼100 to 50 mg/dl. After a two-point calibration, sensor glucose followed the glucose profile as it was decreased slowly from ∼100 to ∼60 mg/dl; however, when the glucose level was subsequently increased rapidly to ∼150 mg/dl, CGMS filtering routines limited the rate of change of sensor glucose and introduced a delay similar to that previously attributed to ISF glucose equilibration delay. Conclusions: Studies that have previously used the Medtronic MiniMed CGMS system to assess changes in the plasma-to-ISF glucose gradient may need to be reassessed to ensure that the offset current was estimated accurately. Studies that have used the system to assess ISF glucose delay during rapid, unphysiologic changes in glucose and did not remove the CGMS smoothing filters may have attributed CGMS filter delay to ISF glucose equilibration.
Comparison of Patient's Preference, Pain Perception, and Usability between Micro Fine plus® 31-Gauge Needle and Microtapered NanoPass® 33-Gauge Needle for Insulin Therapy
Authors: Miyakoshi Masashi , Kamoi Kyuzi , Iwanaga Midori , Hoshiyama Ayako , Yamada Ayako 
Published: January 2014

Background: How smoothly insulin is injected is one of the major concerns when patients commence insulin injection therapy. Improving its usability may be important in initiation therapy and adherence, resulting in clinical Methods: In a single-center, open-label and randomized two-period crossover trial, the effect of the tapered needle of NanoPass® (33 gauge, 5 mm) on usability in comparison with the standard needle of Micro Fine Plus® (31 gauge, 5 mm) was examined using a questionnaire. Patients with insulin-dependent diabetes ( n = 40, self-injecting insulin four times daily for more than 3 months) were randomized to use NanoPass or Micro Fine Plus needles for 1 week and then use the alternative for 1 week. Patients completed the questionnaire before and after each test week. Each evaluation was scored from −100 (worst) to +100 (best) by a visual analogue scale. A higher score indicated a more favorable outcome compared with the other needle. Results: The NanoPass needles. Meanwhile, the NanoPass needle, which had less resistance in insertion with a new lubricant coating P < 0.001) overall patient's satisfaction score, including less frightening use, less bleeding, and less dribbling of injected insulin in comparison with the former evaluation. Conclusions: For overall patient satisfaction in using an insulin needle, developing a thinner needle and improving other factors, such as lubricity coating the needle, are important.
Model Predictive Control of Type 1 Diabetes: An in Silico Trial
Authors: Magni Lalo , Raimondo Davide M. , Bossi Luca , Dalla Man Chiara , De Nicolao Giuseppe , Kovatchev Boris , Cobelli Claudio 
Published: January 2014

Background: The development of artificial pancreas has received a new impulse from recent technological advancements in subcutaneous continuous glucose monitoring and subcutaneous insulin pump delivery systems. However, the availability of innovative sensors and actuators, although essential, does not guarantee optimal glycemic regulation. Closed-loop control of blood glucose levels still poses technological challenges to the automatic control expert, most notable of which are the inevitable time delays between glucose sensing and insulin actuation. Methods: A new in silico model is exploited for both design and validation of a linear model predictive control (MPC) glucose control system. The starting point is a recently developed meal glucose-insulin model in health, which is modified to describe the metabolic dynamics of a person with type 1 diabetes mellitus. The population distribution of the model parameters originally obtained in healthy 204 patients is modified to describe diabetic patients. Individual models of virtual patients are extracted from this distribution. A discrete-time MPC is designed for all the virtual patients from a unique input-output-linearized approximation of the full model based on the average population values of the parameters. The in silico trial simulates 4 consecutive days, during which the patient receives breakfast, lunch, and dinner each day. Results: Provided that the regulator undergoes some individual tuning, satisfactory results are obtained even if the control design relies solely on the average patient model. Only the weight on the glucose concentration error needs to be tuned in a quite straightforward and intuitive way. The ability of the MPC to take advantage of meal announcement information is demonstrated. Imperfect knowledge of the amount of ingested glucose causes only marginal deterioration of performance. In general, MPC results in better regulation than proportional integral derivative, limiting significantly the oscillation of glucose levels. Conclusions: The proposed in silico trial shows the potential of MPC for artificial pancreas design. The main features are a capability to consider meal announcement information, delay compensation, and simplicity of tuning and implementation.