bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Glucose Sensor Membranes for Mitigating the Foreign Body Response
Authors: Koh Ahyeon , Nichols Scott P. , Schoenfisch Mark H.
Published: January 2014

Continuous glucose monitoring devices remain limited in their duration of use due to difficulties presented by the foreign body response (FBR), which impairs sensor functionality immediately following implantation via biofouling and leukocyte infiltration. The FBR persists through the life of the implant, culminating with fibrous encapsulation and isolation from normal tissue. These issues have led researchers to develop strategies to mitigate the FBR and improve tissue integration. Studies have often focused on abating the FBR using various outer coatings, thereby changing the chemical or physical characteristics of the sensor surface. While such strategies have led to some success, they have failed to fully integrate the sensor into surrounding tissue. To further address biocompatibility, researchers have designed coatings capable of actively releasing biological agents (e.g., vascular endothelial growth factor, dexamethasone, and nitric oxide) to direct the FBR to induce tissue integration. Active release approaches have proven promising and, when combined with biocompatible coating materials, may ultimately improve the in vivo lifetime of subcutaneous glucose biosensors. This article focuses on strategies currently under development for mitigating the FBR.
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.
Analysis of the Evaluation of a New Glucose Meter with Integrated Self-Management Software and USB Connectivity
Authors: Crowe Daniel J.
Published: January 2014

Glucose meter technology has not kept up with the advances that have occurred in other sectors in mobile and health care technology. A new device that combines strip-based capillary blood glucose monitoring and USB flash drive technology is evaluated in an industry-funded study in a cohort of patients and health care professionals. The expanded memory capacity of flash drives allows the software program to be stored on the device for analyzing the blood glucose readings in memory. The study analyzes the device for precision and accuracy as well as for ease of adaptability and usage. This analysis focuses on shortcomings in the design of the study and methodology in addition to features of the hardware device itself. Although the device has distinct advantages over many devices on the market, a challenge is made to device manufacturers to encourage further innovation.
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.
Making Life Easier for Insulin Users: One Step Forward with Incremental Advances in Insulin Delivery Systems
Authors: Lock John Paul
Published: January 2014

More than five million Americans use insulin every day for glucose control. The great majority use traditional vials and syringes containing different insulin preparations. The adoption of insulin pens and cartridges in the United States remains disproportionately low in contrast to Europe and Japan. Hopefully, incremental advances in delivery technology of prefilled insulin pens such as the new FlexTouch may help reduce the gap. The article by Wielandt and colleagues in this issue of Journal of Diabetes Science and Technology describes performance and accuracy of the FlexTouch insulin delivery system as well as some user-friendly features of the new prefilled pen.
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.
Historical Achievements of Self-Monitoring of Blood Glucose Technology Development in Japan
Authors: Yamada Shigeki
Published: January 2014

Japanese companies were the first in the world to achieve a colorimetric glucose measurement meter back in 1973. Over the following 40 or so years, they succeeded in achieving a much greater level of user-friendliness and performance and in so doing, have contributed to the spread of self-monitoring of blood glucose. This article aims to unravel the history of blood glucose measurement's technological developments; to look at the direction and features of the development path Japan is taking; as well as to introduce some Japanese products that are on the market.
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.
Closed-Loop Insulin Delivery Utilizing Pole Placement to Compensate for Delays in Subcutaneous Insulin Delivery
Authors: Loutseiko Mikhail , Voskanyan Gayane , Keenan D. Barry , Steil Garry M.
Published: January 2014

Background:

We have previously used insulin feedback (IFB) as a component of a closed-loop algorithm emulating the β cell. This was based on the observation that insulin secretion is inhibited by insulin concentration. We show here that the effect of IFB is to make a closed-loop system behave as if delays in the insulin pharmacokinetic (PK)/ pharmacodynamic (PD) response are reduced. We examine whether the mechanism can be used to compensate for delays in the subcutaneous PK/PD insulin response.

Method:

Closed-loop insulin delivery was performed in seven diabetic dogs using a proportional-integral-derivative model of the β cell modified by model-predicted IFB. The level of IFB was set using pole placement. Meal responses were obtained on three occasions: Without IFB (NONE), reference IFB (REF), and 2xREF, with experiments performed in random order. The ability of the insulin model to predict insulin concentration was evaluated by correlation with the measured profile and results reported as R2. The ability of IFB to improve the meal response was evaluated by comparing peak and nadir postprandial glucose and area under the curve (AUC; repeated measures analysis of variance with post hoc test for linear trend).

Results:

Insulin concentration was well predicted by the model (median R2 = 0.87, 0.79, and 0.90 for NONE, REF, and 2xREF, respectively). Peak postprandial glucose (294 ± 15, 243 ± 21, and 247 ± 16 mg/dl) and AUC (518.2 ± 36.13, 353.5 ± 45.04, and 280.3 ± 39.37 mg/dl±min) decreased with increasing IFB ( p < .05, linear trend). Nadir glucose was not affected by IFB (76 ± 5.4, 68 ± 7.3, and 72 ± 4.3 mg/dl; p = .63).

Conclusions:

Insulin feedback provides an effective mechanism to compensate for delay in the insulin PK/PD profile.
Meta-Analysis of Overnight Closed-Loop Randomized Studies in Children and Adults with Type 1 Diabetes: The Cambridge Cohort
Authors: Kumareswaran Kavita , Elleri Daniela , Allen Janet M. , Harris Julie , Xing Dongyuan , Kollman Craig , Nodale Marianna , Murphy Helen R. , Amiel Stephanie A. , Heller Simon R. , Wilinska Malgorzata E. , Acerini Carlo L. , Evans Mark L. , Dunger David B. , Hovorka Roman
Published: January 2014

Aim:

We reviewed the safety and efficacy of overnight closed-loop insulin delivery compared with conventional continuous subcutaneous insulin infusion (CSII) in two distinct age groups with type 1 diabetes mellitus (T1DM), young people aged 5 to 18 years and adults, combining data of previously published randomized studies.

Methods:

We evaluated four randomized crossover studies in 17 children and adolescents [13.4 ± 3.6 years; mean ± standard deviation (SD)] and 24 adults (37.5 ± 9.1 years) on 45 closed-loop (intervention) and 45 CSII (control) visits. Each subject attended for two overnight study visits, using either closed-loop or conventional pump therapy, in random order. In each age group, studies were designed to mimic realistic likely scenarios. In the children and adolescent studies, closed loop was used following a standard evening meal and following 40 min of moderate-intensity exercise. In the adult studies, closed loop was commenced following a 60 g carbohydrate meal or a 100 g carbohydrate meal accompanied by alcohol. The primary outcome measure was time for which plasma glucose was within target range (3.91–8.0 mmol/liter).

Results:

Overnight closed loop increased the time in target plasma glucose in both young (from 40% to 60%, p = .002) and adults (from 50% to 76%, p < .001) compared with conventional CSII. Combined analysis showed an increase from 43% to 71% with closed loop ( p < .001). Additionally, closed loop reduced the time spent below 3.91 mmol/liter and above 8.0 mmol/liter, from 4.1% to 2.1% ( p = .01) and 33% to 20% ( p = .03), respectively. Glycemic variability, as measured by the SD of plasma glucose, was lower during closed loop compared with CSII (1.5 versus 2.1 mmol/liter, p = .007).

Conclusions:

Overnight closed loop may improve glycemic control and reduce nocturnal hypoglycemia in both young people and adults with T1DM.
Generic Safety Requirements for Developing Safe Insulin Pump Software
Authors: Zhang Yi , Jetley Raoul , Jones Paul L. , Ray Arnab
Published: January 2014

Background:

The authors previously introduced a highly abstract generic insulin infusion pump (GIIP) model that identified common features and hazards shared by most insulin pumps on the market. The aim of this article is to extend our previous work on the GIIP model by articulating safety requirements that address the identified GIIP hazards. These safety requirements can be validated by manufacturers, and may ultimately serve as a safety reference for insulin pump software. Together, these two publications can serve as a basis for discussing insulin pump safety in the diabetes community.

Method:

In our previous work, we established a generic insulin pump architecture that abstracts functions common to many insulin pumps currently on the market and near-future pump designs. We then carried out a preliminary hazard analysis based on this architecture that included consultations with many domain experts. Further consultation with domain experts resulted in the safety requirements used in the modeling work presented in this article.

Results:

Generic safety requirements for the GIIP model are presented, as appropriate, in parameterized format to accommodate clinical practices or specific insulin pump criteria important to safe device performance.

Conclusion:

We believe that there is considerable value in having the diabetes, academic, and manufacturing communities consider and discuss these generic safety requirements. We hope that the communities will extend and revise them, make them more representative and comprehensive, experiment with them, and use them as a means for assessing the safety of insulin pump software designs. One potential use of these requirements is to integrate them into model-based engineering (MBE) software development methods. We believe, based on our experiences, that implementing safety requirements using MBE methods holds promise in reducing design/implementation flaws in insulin pump development and evolutionary processes, therefore improving overall safety of insulin pump software.
Glucose Control in Mayo Clinic Intensive Care Units
Authors: Pattan Vishwanath , Parsaik Ajay , Brown Julie K. , Kudva Yogish C. , Vlahakis Nicholas , Basu Ananda
Published: January 2014

Background:

Safe and effective glucose control in the intensive care unit (ICU) continues to be actively pursued. Large clinical trials have examined the safety and efficacy of insulin infusion protocols in medical and surgical ICUs. We report experiences of a single-center standardized nurse-driven insulin infusion protocol in three ICUs in an observational quality-improvement study.

Method:

We analyzed the hourly point-of-care arterial blood glucose obtained during ICU insulin infusion protocol (protocol A) with a glucose target of 80–130 mg/dl in medical and surgical ICUs in February 2009. Following Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study results, the protocol was amended (protocol B) to achieve target glucose of 110–150 mg/dl. The performance of protocol B was assessed in the ICUs in May 2010 and compared with protocol A with respect to glucose concentrations and rates of severe (<40 mg/dl) and moderate (40–60 mg/dl) hypoglycemia.

Results:

With protocol A, in medical ( n = 44) and surgical ( n = 164) ICUs taken together, median glucose was 119 mg/dl, with severe and moderate hypoglycemia rates 1.4% (3/208) and 7.7% (16/208), respectively, which were significantly lower than those reported by the NICE-SUGAR and the Leuven studies. With protocol B, in medical ( n = 44) and surgical ( n = 167) ICUs taken together, median glucose was 132 mg/dl, with severe and moderate hypoglycemia of 0 % (0/211) and 0.5% (1/211), respectively.

Conclusion:

The current ICU insulin infusion protocol (protocol B) reduces severe and moderate hypoglycemia without compromising glucose control when compared with protocol A. This could potentially impact patient-important outcomes.
Disinfected So it is Safe and Works
Authors: Krisiunas Ed
Published: January 2014

There has been an upsurge in interest in monitoring the cleanliness of the health care environment as it relates to disease transmission. Cleaning and disinfecting practices are nothing new in health care facilities. However, continued development of analytical medical products such as point-of-care devices or, as in this review, glucose meters, has created potential risks to patients on a number of levels. Examples are (1) inappropriate disinfection of glucose meters so that the risk of disease transmission is increased and (2) cleaning agents potentially affecting glucose reading accuracy. Cleaning and disinfection recommendations have become available to address these issues. In this issue of Journal of Diabetes Science and Technology, Sarmaga and colleagues discuss the impact of a disinfecting agent on results generated from a particular device, which suggests that not all equipment are created equal and not all practices/products used to clean and disinfect are the same. It appears that more interaction must take place between vendors of these technologies as well as vendors of cleaning/disinfecting agents and the end users who will be performing all the requisite tasks to ensure a high quality product as well as care.
Analysis of the NovoTwist Pen Needle in Comparison with Conventional Screw-Thread Needles
Authors: Aye Tandy
Published: January 2014

Administration of insulin via a pen device may be advantageous over a vial and syringe system. Hofman and colleagues introduce a new insulin pen needle, the NovoTwist, to simplify injections to a small group of children and adolescents. Their overall preferences and evaluation of the handling of the needle are reported in the study. This new needle has the potential to ease administration of insulin via a pen device that may increase both the use of a pen device and adherence to insulin therapy.
Activation of Polymorphonuclear Leukocytes by Candidate Biomaterials for an Implantable Glucose Sensor
Authors: Sokolov Andrey , Hellerud Bernt Christian , Lambris John D. , Johannessen Erik A. , Mollnes Tom Eirik
Published: January 2014

Background:

Continuous monitoring of glucose by implantable microfabricated devices offers key advantages over current transcutaneous glucose sensors that limit usability due to their obtrusive nature and risk of infection. A successful sensory implant should be biocompatible and retain long-lasting function. Polymorphonuclear leukocytes (PMN) play a key role in the inflammatory system by releasing enzymes, cytokines, and reactive oxygen species, typically as a response to complement activation. The aim of this study was to perform an in vitro analysis of PMN activation as a marker for biocompatibility of materials and to evaluate the role of complement in the activation of PMN.

Methods:

Fifteen candidate materials of an implantable glucose sensor were incubated in lepirudin-anticoagulated whole blood. The cluster of differentiation molecule 11b (CD11b) expression on PMN was analyzed with flow cytometry and the myeloperoxidase (MPO) concentration in plasma was analyzed with enzyme-linked immunosorbent assay. Complement activation was prevented by the C3 inhibitor compstatin or the C5 inhibitor eculizumab.

Results:

Three of the biomaterials (cellulose ester, polyamide reverse osmosis membrane, and polyamide thin film membrane), all belonging to the membrane group, induced a substantial and significant increase in CD11b expression and MPO release. The changes were virtually identical for these two markers. Inhibition of complement with compstatin or eculizumab reduced the CD11b expression and MPO release dose dependently and in most cases back to baseline. The other 12 materials did not induce significant PMN activation.

Conclusion:

Three of the 15 candidate materials triggered PMN activation in a complement-dependent manner and should therefore be avoided for implementation in implantable microsensors.
Pancreatic Polypeptide Administration Enhances Insulin Sensitivity and Reduces the Insulin Requirement of Patients on Insulin Pump Therapy
Authors: Rabiee Atoosa , Galiatsatos Panagis , Salas-Carrillo Rocio , Thompson Michael J. , Andersen Dana K. , Elahi Dariush
Published: January 2014

Introduction:

The effects of pancreatic polypeptide (PP) infusion were examined in patients on insulin pump therapy to determine whether PP administration can reduce insulin requirements in patients with type 1 diabetes mellitus (T1DM) or type 3c diabetes mellitus (T3cDM; pancreatogenic).

Methods:

Ten subjects with long-standing T1DM ( n = 7)or T3cDM ( n = 3)on insulin pump treatment received a 72 h subcutaneous infusion of 2 pmol/kg/min bovine PP or saline by portable infusion pump in a single-blinded, randomized, crossover design.

Results:

Pancreatic polypeptide infusion raised plasma PP levels to 450–700 pmol/liter. Daily insulin infusion requirements (I) fell from 48 ± 6.9 to 40 ± 7.5 U on day 2 ( p < .05)and from 46 ± 7.7 to 37 ± 6.6 U on day 3 ( p < .05)of PP infusion compared with saline. Corrected for average blood glucose concentration (G), I/G fell in 10/10 subjects during the second 24 h period and in 7/10 subjects during the third 24 h period; sensitivity to insulin, calculated as 1/(I/G), increased 45% ± 12% on day 2 ( p < .01) and 34% ± 14% on day 3 ( p < .05) of PP infusion. Pancreatic polypeptide responses to a test meal were compared with the change in insulin infusion requirements in 5 subjects; The reduction in insulin requirements seen during PP infusion correlated with the degree of baseline PP deficiency ( p < .002).

Conclusions:

A concurrent subcutaneous infusion of PP enhances insulin sensitivity and reduces insulin requirements in patients with long-standing T1DM and T3cDM on insulin pump therapy. The benefit of PP infusion correlated with the degree of PP deficiency.
Consensus Report: The Current Role of Self-Monitoring of Blood Glucose in Non-Insulin-Treated Type 2 Diabetes
Authors: Klonoff David C. , Blonde Lawrence , Cembrowski George , Chacra Antonio Roberto , Charpentier Guillaume , Colagiuri Stephen , Dailey George , Gabbay Robert A. , Heinemann Lutz , Kerr David , Nicolucci Antonio , Polonsky William , Schnell Oliver , Vigersky Robert , Yale Jean-François
Published: January 2014

The Coalition for Clinical Research—Self-Monitoring of Blood Glucose Scientific Board convened a meeting in San Francisco, CA, July 20–21, 2011, to discuss the current practice of self-monitoring of blood glucose (SMBG) in non-insulin-treated (NIT) type 2 diabetes mellitus (T2DM). Twelve physician panel members from academia, practice, and government attended this meeting. These experts came from the United States, Brazil, Canada, France, Germany, Italy, and the United Kingdom. In addition, three consultants from Australia, Germany, and the United States contributed to the group's final report. This coalition was organized by Diabetes Technology Society. Self-monitoring of blood glucose was studied from eight perspectives related to patients with NIT T2DM: (1) epidemiological studies; (2) randomized controlled trials (RCT)s and meta-analyses; (3) targets, timing, and frequency of SMBG use; (4) incidence and role of SMBG in preventing hypoglycemia with single-drug regimens and combination regimens consisting of antihyperglycemic agents other than secretagogues and insulin; (5) comparison of SMBG with continuous glucose monitoring; (6) technological capabilities and limitations of SMBG; (7) barriers to appropriate use of SMBG; and (8) methods and end points for appropriate future clinical trials. The panel emphasized recent studies, which reflect the current approach for applying this intervention. Among the participants there was consensus that:

SMBG is an established practice for patients with NIT T2DM, and to be most effective, it should be performed in a structured format where information obtained from this measurement is used to guide treatment; New, high-quality efficacy data from RCTs have demonstrated efficacy of SMBG in NIT T2DM in trials reported since 2008; Both patients and health care professionals require education on how to respond to the data for SMBG to be effective; and Additional well-defined studies are needed to assess the benefits and costs of SMBG with end points not limited to hemoglobin A1c.
A Review of the Security of Insulin Pump Infusion Systems
Authors: Paul Nathanael , Kohno Tadayoshi , Klonoff David C.
Published: January 2014

Insulin therapy has enabled patients with diabetes to maintain blood glucose control to lead healthier lives. Today, rather than injecting insulin manually using syringes, a patient can use a device such as an insulin pump to deliver insulin programmatically. This allows for more granular insulin delivery while attaining blood glucose control. Insulin pump system features have increasingly benefited patients, but the complexity of the resulting system has grown in parallel. As a result, security breaches that can negatively affect patient health are now possible.

Rather than focus on the security of a single device, we concentrate on protecting the security of the entire system. In this article, we describe the security issues as they pertain to an insulin pump system that includes an embedded system of components, which include the insulin pump, continuous glucose management system, blood glucose monitor, and other associated devices (e.g., a mobile phone or personal computer). We detail not only the growing wireless communication threat in each system component, but also describe additional threats to the system (e.g., availability and integrity). Our goal is to help create a trustworthy infusion pump system that will ultimately strengthen pump safety, and we describe mitigating solutions to address identified security issues.
Evaluation of the Analytical Performance of the Coulometry-Based Optium Omega Blood Glucose Meter: What Do Such Evaluations Show?
Authors: Krouwer Jan S.
Published: January 2014

The article entitled “Evaluation of the Analytical Performance of the Coulometry-Based Optium Omega Blood Glucose Meter”, by Solnica and colleagues in this issue of Journal of Diabetes Science and Technology demonstrates that the Optium Omega blood glucose meter meets the analytical requirements for glucose meter performance and it is stated that the results are clinically useful. The authors studied precision, bias, and reagent lot-to-lot error sources. The ultimate goal of an evaluation is to estimate the distribution of errors (from any source) that will be experienced in routine use. The data collection and analysis methods to achieve this are discussed, as are the standards used to compare the results. Claiming clinical usefulness is almost a boilerplate statement in evaluations but meeting standards does not prove clinical usefulness.
Association of Hyperglycemia, Glucocorticoids, and Insulin Use with Morbidity and Mortality in the Pediatric Intensive Care Unit
Authors: Wintergerst Kupper A. , Foster Michael B. , Sullivan Janice E. , Woods Charles R.
Published: January 2014

Background:

Studies of pediatric intensive care unit (PICU) patients have shown a significant association of morbidity and mortality with hyperglycemia. We retrospectively evaluated the degree of hyperglycemia as well as its correlation with glucocorticoid and insulin use and assessed its association with hospital length of stay (LOS) and mortality. This study preceded the initiation of a standard glycemic control protocol.

Methods:

We examined medical records at Kosair Children's Hospital for all PICU admissions from 2008 of patients without diabetes mellitus. Critical illness hyperglycemia (CIH) was defined by having three or more peak glucose values greater than thresholds of 110, 140, 180, and 200 mg/dl. These patients were evaluated for glucocorticoid, insulin use, and outcome measures.

Results:

We evaluated the eligible 1173 admissions, where 10.5% of these patients reached the highest threshold (200 mg/dl) of CIH. Glucocorticoids were used in 43% of these patients, with dexamethasone being the most common (58%). There was a significant correlation between glucocorticoids and higher peak glucose values, where 81% of the patients who were above the 200 mg/dl cutoff level were treated with glucocorticoids. Only 36.8% in that group were also treated with insulin. Patients at the 200 mg/dl cutoff had the highest median PICU and total hospital length of stays (4 and 10 days, respectfully). Mortality was associated with increasing glucose levels, reaching 18.7% among patients above the 200 mg/dl cutoff.

Conclusion:

Hyperglycemia was prevalent in the PICU and was associated with increased morbidity, as characterized by increased LOS and increased mortality. Glucocorticoid use was prevalent among patients exhibiting hyperglycemia. Insulin use was uncommon.
Critical Illness Hyperglycemia in Pediatric Cardiac Surgery
Authors: Ulate Kalia P. , Raj Shekhar , Rotta Alexandre T.
Published: January 2014

Critical illness hyperglycemia (CIH) is common in pediatric and adult intensive care units (ICUs). Children undergoing surgical repair or palliation of congenital cardiac defects are particularly at risk for CIH and its occurrence has been associated with increased morbidity and mortality in this population. Strict glycemic control through the use of intensive insulin therapy (IIT) has been shown to improve outcomes in some adult and pediatric studies, yet these findings have sparked controversy. The practice of strict glycemic control has been slow in extending to pediatric ICUs because of the documented increase in the incidence of hypoglycemia in patients treated with IIT. Protocol driven approaches with more liberal glycemic targets have been successfully validated in general and cardiac critical care pediatric patients with low rates of hypoglycemia. It is unknown whether a therapeutic benefit is obtained by keeping patients in this more liberal glycemic control target. Definitive randomized controlled trials of IIT utilizing these targets in critically ill children are ongoing.