bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Pioglitazone and Ramipril on Biomarkers of Low-Grade Inflammation and Vascular Function in Nondiabetic Patients with Increased Cardiovascular Risk and an Activated Inflammation: Results from the PIOace Study
Authors: Pfützner Andreas , Hanefeld Markolf , Dekordi Lida A. , Müller Jürgen , Kleine Iris , Fuchs Winfried , Forst Thomas 
Published: January 2014

Aims: This study investigated the effects of pioglitazone (PIO), ramipril (RAM), or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive patients with increased cardiovascular risk. Methods and Results: Patients enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72 male, 77 female, aged 60 ± 9 years, body mass index 30.4 ± 4.7 kg/m2, duration of hypertension 9 ± 8 years) were treated with either 30/45 mg PIO (dose titration), 2.5/5 mg RAM, or their combination for 12 weeks. A reduction in high-sensitivity C-reactive protein was observed with PIO (−0.89 ± 1.98 mg/liter; −25%) and PIRA (−0.49 ± 2.11 mg/liter; −16%), while an increase was seen with RAM (0.58 ± 2.13 mg/liter; +20%, p < .05 vs PIO and PIRA). The 24-hour blood pressure profile showed a small increase with both monotherapies but a decrease with PIRA ( p < .05 vs PIO). Improvements in biomarkers of chronic systemic inflammation and insulin resistance (IR) were observed in the PIO and PIRA arms only [PIO/RAM/PIRA: homeostasis model of assessment of IR: −0.78 ± 1.39 (−29%)/0.15 ± 1.03 (+5%)/ −1.44 ± 2.83 (−40%); adiponectin: 8.51 ± 5.91 (+104%)/ 0.09 ± 2.63 (+1%)/ 8.86 ± 6.37 mg/liter (+107%); matrix metalloproteinase-9: −48 ± 127 (−12%)/−1 ± 224 (0%)/−60 ± 210 ng/ml (−13%), p < .05 for RAM vs PIO or PIRA in all cases]. Conclusions: Our 3-month study in nondiabetic hypertensive patients showed a decrease in biomarkers of IR and chronic systemic inflammation with the PIO monotherapy and the PIRA combination only, which may help to explain some findings in other cardiovascular outcome trials.
BioRadioTransmitter: A Self-Powered Wireless Glucose-Sensing System
Authors: Hanashi Takuya , Yamazaki Tomohiko , Tsugawa Wakako , Ikebukuro Kazunori , Sode Koji 
Published: January 2014

Background: Although an enzyme fuel cell can be utilized as a glucose sensor, the output power generated is too low to power a device such as a currently available transmitter and operating system, and an external power source is required for operating an enzyme-fuel-cell-based biosensing system. We proposed a novel biosensor that we named BioCapacitor, in which a capacitor serves as a transducer. In this study, we constructed a new BioCapacitor-based system with an added radio-transmitter circuit and a miniaturized enzyme fuel cell. Methods: A miniaturized direct-electron-transfer-type compartmentless enzyme fuel cell was constructed with flavin adenine dinucleotide-dependent glucose dehydrogenase complex-based anode and a bilirubin-oxidase-based cathode. For construction of a BioRadioTransmitter wireless sensing system, a capacitor, an ultra-low-voltage charge-pump-integrated circuit, and Hartley oscillator circuit were connected to the miniaturized enzyme fuel cell. A radio-receiver circuit, comprising two field-effect transistors and a coil as an antenna, was used to amplify the signal generated from the biofuel cells. Results: Radio wave signals generated by the BioRadioTransmitter were received, amplified, and converted from alternate to direct current by the radio receiver. When the capacitor discharges in the presence of glucose, the BioRadioTransmitter generates a radio wave, which is monitored by a radio receiver connected wirelessly to the sensing device. Magnitude of the radio wave transmission frequency change observed at the radio receiver was correlated to glucose concentration in the fuel cells. Conclusions: We constructed a stand-alone, self-powered, wireless glucose-sensing system called a BioRadioTransmitter by using a radio transmitter in which the radio wave transmission frequency changes with the glucose concentration in the fuel cell. The BioRadioTransmitter is a significant advance toward construction of an implantable continuous glucose monitor.
Flexible Three-Dimensional Electrochemical Glucose Sensor with Improved Sensitivity Realized in Hybrid Polymer Microelectromechanical Systems Technique
Authors: Patel Jasbir N. , Gray Bonnie L. , Kaminska Bozena , Gates Byron D. 
Published: January 2014

Background: Continuous glucose monitoring for patients with diabetes is of paramount importance to avoid severe health conditions resulting from hypoglycemia or hyperglycemia. Most available methods require an invasive setup and a health care professional. Handheld devices available on the market also require finger pricking for every measurement and do not provide continuous monitoring. Hence, continuous glucose monitoring from human tears using a glucose sensor embedded in a contact lens has been considered as a suitable option. However, the glucose concentration in human tears is very low in comparison with the blood glucose level (1/10–1/40 concentration). We propose a sensor that solves the sensitivity problem in a new way, is flexible, and is constructed onto the oxygen permeable contact lens material. Methods: To achieve such sensitivity while maintaining a small sensor footprint suitable for placement in a contact lens, we increased the active electrode area by using three-dimensional (3-D) electrode micropatterning. Fully flexible 3-D electrodes were realized utilizing ordered arrays of pillars with different shapes and heights. Results: We successfully fabricated square and cylindrical pillars with different height (50, 100, and 200 μm) and uniform metal coverage to realize sensor electrodes. The increased surface area produces high amperometric current that increases sensor sensitivity up to 300% using 200 μ tall square pillars. The sensitivity improvement closely follows the improvement in the surface area of the electrode. Conclusions: The proposed flexible glucose sensors with 3-D microstructure electrodes are more sensitive to lower glucose concentrations and generate higher current signal than conventional glucose sensors.
Synthesis and Development of Poly(N-Hydroxyethyl Acrylamide)-Ran-3-Acrylamidophenylboronic Acid Polymer Fluid for Potential Application in Affinity Sensing of Glucose
Authors: Li Siqi , Davis Erin N. , Huang Xian , Song Bing , Peltzman Rebecca , Sims David M. , Lin Qiao , Wang Qian 
Published: January 2014

Background: In previous work, we described viscosity and permittivity microelectromechanical systems (MEMS) sensors for continuous glucose monitoring (CGM) using poly[acrylamide- ran-3-acrylamidophenylboronic acid (PAA- ran-PAAPBA). In order to enhance our MEMS device antifouling properties, a novel, more hydrophilic polymer-sensing fluid was developed. Method: To optimize sensing performance, we synthesized biocompatible copolymers poly( N-hydroxyethyl acrylamide)- ran-3-acrylamidophenylboronic acid (PHEAA- ran-PAAPBA) and developed its sensing fluid for viscosity-based glucose sensing. Key factors such as polymer composition and molecular weight were investigated in order to optimize viscometric responses. Results: Compared with PAA- ran-PAAPBA fluid of a similar binding moiety percentage, PHEAA- ran-PAAPBA showed comparable high binding specificity to glucose in a reversible manner and even better performance in glucose sensing in terms of glucose sensing range (27–468 mg/ml) and sensitivity (within 3% standard error of estimate). Preliminary experiment on a MEMS viscometer demonstrated that the polymer fluid was able to sense the glucose concentration. Conclusions: Our MEMS systems using PHEAA- ran-PAAPBA will possess enhanced implantable traits necessary to enable CGM in subcutaneous tissues.
A Disposable Tear Glucose Biosensor—Part 3: Assessment of Enzymatic Specificity
Authors: Lan Kenneth , McAferty Kenyon , Shah Pankti , Lieberman Erica , Patel Dharmendra R. , Cook Curtiss B. , La Belle Jeffrey T. 
Published: January 2014

Background: A concept for a tear glucose sensor based on amperometric measurement of enzymatic oxidation of glucose was previously presented, using glucose dehydrogenase flavin adenine dinucleotide (GDH-FAD) as the enzyme. Glucose dehydrogenase flavin adenine dinucleotide is further characterized in this article and evaluated for suitability in glucose-sensing applications in purified tear-like saline, with specific attention to the effect of interfering substances only. These interferents are specifically saccharides that could interact with the enzymatic activity seen in the sensor's performance. Methods: Bench top amperometric glucose assays were performed using an assay solution of GDH-FAD and ferricyanide redox mediator with samples of glucose, mannose, lactose, maltose, galactose, fructose, sucrose, and xylose at varying concentrations to evaluate specificity, linear dynamic range, signal size, and signal-to-noise ratio. A comparison study was done by substituting an equivalent activity unit concentration of glucose oxidase (GOx) for GDH-FAD. Results: Glucose dehydrogenase flavin adenine dinucleotide was found to be more sensitive than GOx, producing larger oxidation currents than GOx on an identical glucose concentration gradient, and GDH-FAD exhibited larger slope response (-5.65 × 10−7 versus −3.11 × 10−7 A/mM), signal-to-noise ratio (18.04 versus 2.62), and linear dynamic range (0–30 versus 0–10 mM), and lower background signal (−7.12 versus −261.63 nA) than GOx under the same assay conditions. GDH-FAD responds equally to glucose and xylose but is otherwise specific for glucose. Conclusion: Glucose dehydrogenase flavin adenine dinucleotide compares favorably with GOx in many sensor-relevant attributes and may enable measurement of glucose concentrations both higher and lower than those measurable by GOx. GDH-FAD is a viable enzyme to use in the proposed amperometric tear glucose sensor system and perhaps also in detecting extreme hypoglycemia or hyperglycemia in blood.
Trend Analyses of Insulin Delivery Systems in the United States
Authors: Lee Lauren J. , Li Qian , Reynolds Matthew W. , Engelman William 
Published: January 2014

Background: Despite potential advantages in insulin pen delivery systems (IPDSs), the percentage of patients using an IPDS is relatively low in the United States. Objective: Our aim was to investigate the trend of initiating IPDSs among patients with type 2 diabetes mellitus (T2DM) who newly initiated insulin therapy. Methods: A retrospective analysis was conducted using a U.S. database from January 1, 2004, to December 31, 2008. Patients with T2DM who initiated a new insulin type and delivery system were included. The Cochran-Armitage test was used to assess the significance of the trend of initiating an insulin delivery system, including vial/syringe, IPDS overall, reusable pen delivery systems (RPDSs), and prefilled pen delivery systems (PPDSs). Different types of insulin (e.g., basal analog, prandial analog) were examined separately. Results: Patients initiating an IPDS increased from 10.6% in 2004 to 48.5% in 2008 ( p < .001), most notably in basal analog and prandial analog insulin therapies. Although the percentage of patients using a PPDS increased by 36.2 percentage points (from 9.2% in 2004 to 45.4% in 2008; p < .001), use of a RPDS increased only by 1.7 percentage points (from 1.4% in 2004 to 3.1% in 2008; p < .001). Conclusion: There was an overall increase in the use of IPDSs in the United States among patients with T2DM who newly initiated insulin from July 1, 2004, to December 31, 2008. This increase was driven by the use of PPDSs for basal analog and prandial analog insulin therapies. Despite the increasing use of IPDS over time, approximately 50% of patients still initiated insulin using a vial/syringe in 2008.
Performance Evaluation and Labeling Comprehension of a New Blood Glucose Monitoring System with Integrated Information Management
Authors: List Susan M. , Starks Nykole , Baum John , Greene Carmine , Pardo Scott , Parkes Joan L. , Schachner Holly C. , Cuddihy Robert 
Published: January 2014

Background: This study evaluated performance and product labeling of CONTOUR® USB, a new blood glucose monitoring system (BGMS) with integrated diabetes management software and a universal serial bus (USB) port, in the hands of untrained lay users and health care professionals (HCPs). Method: Subjects and HCPs tested subject's finger stick capillary blood in parallel using CONTOUR USB meters; deep finger stick blood was tested on a Yellow Springs Instruments (YSI) glucose analyzer for reference. Duplicate results by both subjects and HCPs were obtained to assess system precision. System accuracy was assessed according to International Organization for Standardization (ISO) 15197:2003 guidelines [within ±15 mg/dl of mean YSI results (samples <75 mg/dl) and ±20% (samples ≥75 mg/dl)]. Clinical accuracy was determined by Parkes error grid analysis. Subject labeling comprehension was assessed by HCP ratings of subject proficiency. Key system features and ease-of-use were evaluated by subject questionnaires. Results: All subjects who completed the study ( N = 74) successfully performed blood glucose measurements, connected the meter to a laptop computer, and used key features of the system. The system was accurate; 98.6% (146/148) of subject results and 96.6% (143/148) of HCP results exceeded ISO 15197:2003 criteria. All subject and HCP results were clinically accurate (97.3%; zone A) or associated with benign errors (2.7%; zone B). The majority of subjects rated features of the BGMS as “very good” or “excellent.” Conclusions: CONTOUR USB exceeded ISO 15197:2003 system performance criteria in the hands of untrained lay users. Subjects understood the product labeling, found the system easy to use, and successfully performed blood glucose testing.
Dynamic Electrochemistry Corrects for Hematocrit Interference on Blood Glucose Determinations with Patient Self-Measurement Devices
Authors: Musholt Petra B. , Schipper Christina , Thomé Nicole , Ramljak Sanja , Schmidt Marc , Forst Thomas , Pfützner Andreas 
Published: January 2014

Background: It has been demonstrated that dynamic electrochemistry can be used to correct blood glucose measurement results for potentially interfering conditions, such as humidity, hematocrit (HCT) variations, and ascorbic acid. The purpose of this laboratory investigation was to assess the potential influence of hematocrit variations on a variety of blood glucose meters applying different measurement technologies. Methods: Venous heparinized whole blood was drawn, immediately aliquoted, and manipulated to contain three different blood glucose concentrations (80, 155, and 310 mg/dl) and five different hematocrit levels (25%, 37%, 45%, 52%, and 60%). After careful oxygenation to normal blood oxygen pressure, each of the resulting 15 different samples was measured 8 times with the following devices: BGStar, Contour, Accu-Chek Aviva, Accu-Chek Aviva Nano, Breeze 2, Precision Xceed, OneTouch Ultra 2, OneTouch Verio, FreeStyle Freedom Lite, Glucocard G+, GlucoMen LX, GlucoMen GM, and StatStrip [point-of-care (POC) device]. Cobas (Roche Diagnostics, glucose hexokinase method) served as laboratory plasma reference method. Stability to hematocrit influence was assumed when less than 10% bias occurred between the highest and lowest hematocrit levels when analyzing mean deviations for all three glucose concentrations. Results: Besides the POC StatStrip device, which is known to measure and correct for hematocrit (resulting in <2% bias), four self-test meters also showed a stable performance in this investigation: Dynamic electrochemistry, BGStar (8%), and static electrochemistry, Contour (6%), Glucocard G+ (2%), and OneTouch Verio (6%). The other meters failed this test: Colorimetry, FreeStyle Freedom Lite (16%), and static electrochemistry, Accu-Chek Aviva (23%), Accu-Chek Aviva Nano (18%), Breeze 2 (36%), OneTouch Ultra 2 (34%), Precision Xceed (34%), GlucoMen LX (24%), and GlucoMen GM (31%). Conclusions: As hematocrit variations occur in daily routine (e.g., because of smoking, exercise, hypermenorrhea, pregnancy, stay in mountains, and hemodialysis), our results may encourage use of meters with stable performance under these conditions. Dynamic electrochemistry as used in the BGStar device (sanofi-aventis) appears to be an effective technology to correct for potential hematocrit influence on the meter results.
Analysis: Linking Laboratory Data to Human Factors and Inclusion of Persons with Disabilities in Diabetes Technology Research
Authors: Williams Ann S. 
Published: January 2014

In this issue of Journal of Diabetes Science and Technology, Friedrichs and colleagues present a study of the injection force of four reusable insulin pens and another study of the dosing accuracy of three different insulin pens. For the study of injection force, the authors claim that lower injection force has numerous advantages for patients, including making use of pens easier for people with decreased hand strength. For the study of dosing accuracy, the authors state that dose accuracy is critical for glycemic control. Both study designs have significant strengths, including measurements of the variable of interest using two different methodologies and thorough documentation of methods and materials. However, the careful, precise measurements of injection force and dosing accuracy are not matched by equivalent precision supporting the significance of the studies. The authors do not provide any information about what measured injection force is easy or difficult for individuals with and without manual problems or what level of dosing inaccuracy is clinically significant. Therefore, the implications for practice remain unclear. Data about these and other relevant human factors are needed to provide meaningful context for laboratory measurements of diabetes technologies. Furthermore, researchers conducting studies of diabetes technology that include human subjects should intentionally recruit persons with disabilities so diabetes care professionals can know whether and how technical information about diabetes technology applies to the full range of patients, including those with disabilities.
Analysis of Patient Satisfaction with a Prefilled Insulin Injection Device in Patients with Type 1 and Type 2 Diabetes
Authors: Siegmund Thorsten 
Published: January 2014

In this issue of Journal of Diabetes Science and Technology, Hancu and colleagues present an observational 6–8-week Pan-European and Canadian prospective survey on patient satisfaction with a prefilled insulin injection device, the SoloSTAR pen device, in patients with type 1 and 2 diabetes ( n = 6542). The SoloSTAR pen is one of several up-to-date insulin pens of high quality and characteristics that fit many of our patients with diabetes. The mainly excellent–good votes of the participants for the SoloSTAR are not surprising, as we have seen continuous improvements with prefilled pens, such as the SoloSTAR device. Several years ago, patients as well as health care providers found considerable differences between the available pen options. Nowadays, as almost all pen providers have clearly improved their products, the differences are much smaller; we are closer to a “perfect” prefilled pen device. Nevertheless, there is a need for more randomized controlled trials, ideally sponsored not by just one manufacturer, to be able to make clear statements toward different pen device aspects (e.g., accuracy of dosing, adherence to therapy, ease of use, and patient satisfaction). An additional handicap is the difficulty to get blinded study designs.
Integrating Telehealth Technology into a Clinical Pharmacy Telephonic Diabetes Management Program
Authors: Klug Cindy , Bonin Kerry , Bultemeier Nanette , Rozenfeld Yelena , Vasquez Rebecca Stuckman , Johnson Mark , Cherry Julie Cheitlin 
Published: January 2014

Background: Use of home monitoring technologies can enhance care coordination and improve clinical outcomes in patients with diabetes and other chronic diseases. This study was designed to explore the feasibility of incorporating a telehealth system into an existing telephonic diabetes management program utilizing clinical pharmacists. Methods: This observational study was conducted at three Providence Medical Group primary care clinics. Adults with a diagnosis of diabetes and a recent hemoglobin A1c (HbA1c) >8% were referred by their primary care provider to participate in the study. Participants utilized the telehealth system developed by Intel Corporation and were followed by clinical pharmacists who provide telephonic diabetes management. The primary clinical outcome measure was change in mean HbA1c. Secondary outcomes included blood glucose levels, participant self-management knowledge, and the degree of participant engagement. Results: Mean HbA1c level decreased by 1.3% at the study end ( p = .001). Based on participant satisfaction surveys and qualitative responses, participants were satisfied with the telehealth system. Mean blood glucose values decreased significantly over the 16-week study period from 178 mg/dl [standard deviation (SD) 67] at week 1 to 163 mg/dl (SD 64) at week 16 ( p = .0002). Participants entered the study with moderate to good knowledge about managing their diabetes based on three questions, and no statistically significant improvement in knowledge was found post-study. Conclusion: Telehealth technology can be a positive adjunct to the primary care team in managing diabetes or other chronic conditions to improve clinical outcomes.
Continuous Glucose Monitoring Considerations for the Development of a Closed-Loop Artificial Pancreas System
Authors: Keenan D. Barry , Grosman Benyamin , Clark Harry W. , Roy Anirban , Weinzimer Stuart A. , Shah Rajiv V. , Mastrototaro John J. 
Published: January 2014

Background: Commercialization of a closed-loop Artificial Pancreas system that employs continuous subcutaneous insulin infusion and interstitial fluid glucose sensing has been encumbered by state-of-the-art technology. Continuous glucose monitoring (CGM) devices with improved accuracy could significantly advance development efforts. However, the current accuracy of CGM devices might be adequate for closed-loop control. Methods: The influence that known CGM limitations have on closed-loop control was investigated by integrating sources of sensor inaccuracy with the University of Virginia Padova Diabetes simulator. Non-glucose interference, physiological time lag and sensor error measurements, selected from 83 Enlite™ glucose sensor recordings with the Guardian® REAL-Time system, were used to modulate simulated plasma glucose signals. The effect of sensor accuracy on closed-loop controller performance was evaluated in silico, and contrasted with closed-loop clinical studies during the nocturnal control period. Results: Based on n = 2472 reference points, a mean sensor error of 14% with physiological time lags of 3.28 ± 4.62 min (max 13.2 min) was calculated for simulation. Sensor bias reduced time in target for both simulation and clinical experiments. In simulation, additive error increased time <70 mg/dl and >180 mg/dl by 0.2% and 5.6%, respectively. In-clinic, the greatest low blood glucose index values (max = 5.9) corresponded to sensor performance. Conclusion: Sensors have sufficient accuracy for closed-loop control, however, algorithms are necessary to effectively calibrate and detect erroneous calibrations and failing sensors. Clinical closed-loop data suggest that control with a higher target of 140 mg/dl during the nocturnal period could significantly reduce the risk for hypoglycemia.