bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of Glucose in Blood with a Phenylboronic Acid Optical Sensor
Authors: Worsley Graham J. , Tourniaire Guilhem A. , Medlock Kathryn E. S. , Sartain Felicity K. , Harmer Hazel E. , Thatcher Michael , Horgan Adrian M. , Pritchard John
Published: January 2014

Background:

Current methods of glucose monitoring rely predominantly on enzymes such as glucose oxidase for detection. Phenylboronic acid receptors have been proposed as alternative glucose binders. A unique property of these molecules is their ability to bind glucose in a fully reversible covalent manner that facilitates direct continuous measurements. We examined (1) the ability of a phenylboronic-based sensor to measure glucose in blood and blood plasma and (2) the effect on measurement accuracy of a range of potential interferents. We also showed that the sensor is able to track glucose fluctuations occurring at rates mimicking those experienced in vivo.

Method:

In vitro static measurements of glucose in blood and blood plasma were conducted using holographic sensors containing acrylamide, N,N'-methylenebisacrylamide, 3-acrylamidophenylboronic acid, and (3-acrylamidopropyl) trimethylammonium chloride. The same sensors were also used for in vitro measurements performed under flow conditions.

Results:

The opacity of the liquid had no affect on the ability of the optical sensor to measure glucose in blood or blood plasma. The presence of common antibiotics, diabetic drugs, pain killers, and endogenous substances did not affect the measurement accuracy, as shown by error grid analysis. Ex vivo flow experiments showed that the sensor is able to track changes accurately in concentration occurring in real time without lag or evidence of hysteresis.

Conclusions:

The ability of phenylboronic acid sensors to measure glucose in whole blood was demonstrated for the first time. Holographic sensors are ideally suited to continuous blood glucose measurements, being physically and chemically robust and potentially calibration free.
Pioglitazone Improves Metabolic Markers in Patients with Type 2 Diabetes Independently from Physical Activities: Results from the IRIS III Study
Authors: Schöndorf Thomas , Pfützner Andreas , Lübben Georg , Karagiannis Efstrathios , Roth Werner , Forst Thomas
Published: January 2014

Aim:

Pioglitazone is an established peroxisome proliferator-activated receptor γ agonist for the treatment of insulin resistance in patients with type 2 diabetes mellitus. This analysis of the observational IRIS III study was performed to evaluate the effects of pioglitazone treatment in relation to the degree of physical exercise activities in a large patient population under daily life conditions.

Methods:

A total of 1298 patients out of 2092 enrolled into the IRIS III study who had provided information about their exercise level could be included in the final analysis (622 female, 676 male; age: 63.1 ± 10.4 years, diabetes duration: 6.6 ± 5.0 years, mean ± SD). All patients were glitazone naïve prior to study entry. They received pioglitazone in addition to their previous oral antidiabetic treatment. The patients were stratified according to their physical activity level (never, sometimes, and regularly). Data were evaluated at baseline and after 20 ± 2 weeks of treatment. Observation parameters were fasting blood glucose, lipids, and blood pressure. Hemoglobin A1c (HbA1c) was determined in a central laboratory, and insulin sensitivity was assessed by the IRIS II score.

Results:

Glycemic control, blood pressure, and the lipid profile improved independently from the degree of physical activity (e.g., no exercise vs frequent exercise: ΔHbA1c: −0.89 ± 1.2% vs −0.72 ± 1.1%, not significant). A positive impact of exercise on insulin resistance could be observed at baseline, which, however, was further decreased by pioglitazone treatment [IRIS II score (baseline/end point): no exercise vs frequent exercise: 74.0 ± 15.9/62.5 ± 20.2 vs 66.7 ± 19.0/58.0 ± 21.8, p < 0.001/not significant].

Conclusions:

These observational results, obtained from a nonselected patient population under daily routine conditions, confirm that the benefits of pioglitazone treatment on glycemic control, lipid metabolism, and blood pressure are independent from physical activity. Exercise has a positive influence on insulin sensitivity, but pioglitazone shows additional favorable effects and is, therefore, recommended for use independently from the activity level of the patients.
Diabetes Information Technology: Designing Informatics Systems to Catalyze Change in Clinical Care
Authors: Lester William T. , Zai Adrian H. , Chueh Henry C. , Grant Richard W.
Published: January 2014

Current computerized reminder and decision support systems intended to improve diabetes care have had a limited effect on clinical outcomes. Increasing pressures on health care networks to meet standards of diabetes care have created an environment where information technology systems for diabetes management are often created under duress, appended to existing clinical systems, and poorly integrated into the existing workflow. After defining the components of diabetes disease management, the authors present an eight-step conceptual framework to guide the development of more effective diabetes information technology systems for translating clinical information into clinical action.
Diabetes: An Investor's Perspective
Authors: Harris Bernard
Published: January 2014

Total health care expenditure in 2006 was $2.1 trillion. This figure is estimated to double within the next few years as the cost of treating diabetes and other chronic conditions continues to rise. Moreover, the baby boomer demographic is anticipated to place an enormous burden on the health care system and employer-based health insurance premiums were increased at rates as high as 10% per year in 2006.

The quest to address these challenges has also created opportunities for investment, particularly in the fields of telemedicine, health care information technology, and medical technology.

The author shares his business perspective, informed by years of experience as a physician and astronaut at NASA, and describes new applications of exciting technologies that deliver effective and efficient health care to diabetes patients, no matter where they may be.
DUROS® Technology Delivers Peptides and Proteins at Consistent Rate Continuously for 3 to 12 Months
Authors: Rohloff Catherine M. , Alessi Thomas R. , Yang Bing , Dahms Janice , Carr John P. , Lautenbach Scott D.
Published: January 2014

Background:

DUROS® delivery technology consists of sterile, nonbiodegradable, single-use devices for continuous, subcutaneous administration of therapeutic molecules at steady rates. DUROS delivery technology is capable of delivering a wide range of therapeutic molecules for durations ranging from 3 to 12 months. Administration of therapy via DUROS devices may facilitate patient compliance with treatment since the DUROS device does not require self-injections. Consistent delivery of drug levels within a targeted therapeutic window achievable with DUROS delivery technology avoids exposure to high initial drug concentrations that can result from bolus injections and that may be associated with certain adverse drug effects.

Methods:

Several approaches have been taken to assess the suitability of DUROS devices for delivery of the therapeutic molecules leuprolide acetate, glucagon-like peptide-1 (GLP-1), and omega interferon (omega IFN). Testing includes determining protein stability and measuring in vitro protein release rates.

Results:

Three peptides or proteins were formulated into either a solution (leuprolide) or Intarcia's proprietary DUROS suspension formulation (GLP-1, omega IFN) and filled into DUROS devices. The devices demonstrated reliable start-up and continuous steady drug delivery in in vitro studies. Stability of the molecules was maintained for 3 years at 37°C (leuprolide), 2 years at 30°C (omega IFN), or 6 months at 37°C (GLP-1). Patients in clinical studies of a 1-year DUROS device found the device to be comfortable and convenient.

Conclusions:

Multiple studies demonstrated that peptides or proteins remain stable in DUROS devices and that delivery at a steady rate can be achieved over a wide range of delivery rates.
Differences in the Dose Accuracy of Insulin Pens
Authors: Hänel Heike , Weise Alexander , Sun Wei , Pfützner Johannes W. , Thomé Nicole , Pfützner Andreas
Published: January 2014

Background:

Modern insulin injection pens provide a convenient and accurate way for diabetes patients to inject insulin. They have widespread use among children and adults with type 1 and type 2 diabetes in the U.S. and Europe. This study compared the dosing accuracy of four commonly available insulin pens (OptiClik® and SoloSTAR® from sanofi-aventis, FlexPen® from Novo Nordisk, and HumaPen® LUXURA™ from Eli Lilly).

Methods:

The dosing accuracy was tested for all pens with 24 × 10 IU and 9 × 30 IU injection volumes to investigate whether the pens complied with the acceptable International Organization for Standardization (ISO) limits of 10% (± 1 IU) for 10 IU and 5% (± 1.5 IU) for 30 IU. The doses were each applied with a new needle strictly according to the instructions for use by the pen manufacturers. A pharmaceutical balance was used for the assessment of the applied volumes, and the results were corrected for the specific density of the insulin formulations. Four insulin pens (two each from different production lots) were used for each of the two volumes, resulting in a total of 192 doses per pen with 10 IU, and 72 doses per pen with 30 IU.

Results:

FlexPen (mean absolute percent deviation for 10 IU and 30 IU: 1.64 ± 0.84% and 0.83 ± 0.26%, respectively) and HumaPen LUXURA (1.10 ± 0.20% and 0.62 ± 0.19%; not significant versus FlexPen for both doses) were more accurate than the OptiClik (4.78 ± 3.31% and 2.97 ± 2.48%, p <.01) and the SoloSTAR (2.61 ± 0.92% and 1.70 ± 0.84%, p <.05). While 6.8% of doses were outside the ISO limit at 10 IU with OptiClik (13.9% at 30 IU), the corresponding figures were 0.5% and 4.1%, respectively, for SoloSTAR. No doses outside the ISO limits were seen with FlexPen or HumaPen LUXURA at 10 IU and only one 30 IU dose (1.4%) was outside the limit for FlexPen.

Conclusions:

A direct head-to-head comparison of four insulin pens with a standardized protocol resulted in a more stable dosing accuracy of the FlexPen and the HumaPen LUXURA in comparison to the OptiClik and SoloSTAR. Even though all insulin delivery systems undergo rigorous testing before being approved for sale, there may be reasons to be attentive to the performance of the devices in practical use.
Devices for the Treatment of Obesity: Will Understanding the Physiology of Satiety Unravel New Targets for Intervention?
Authors: Weiss Ram
Published: January 2014

The rise in the prevalence of obesity in the last few decades and its growing impact on health has driven the scientific community to investigate the physiological basis of energy homeostasis and mechanisms of satiety, and seek targets for intervention against this burgeoning epidemic. Recent findings highlight the role of gut***derived, hormonal signals in the regulation of satiety. These hormones act together with the dense and intricate enteric nervous system to coordinate and regulate gastrointestinal satiety signals, motility, and digestive processes. Bariatric surgical approaches attempt to take advantage of these mechanisms to facilitate early satiety and weight loss. Some of these procedures, by altering the anatomical structure of the upper gastrointestinal tract, also modify the hormonal response to food. Similarly, devices such as volume-occupying elements and nerve stimulators attempt to alter the gastrointestinal milieu in a manner that will ultimately lead to long-term weight loss. Novel surgical, endoscopic, and device-oriented methodologies seem to be promising approaches to treat obesity, yet further research is needed to appreciate their long-term effect.
“No Coding” of Glucose Test Strips: A Roche Perspective
Authors: Essenpreis Matthias , Scherff Dirk
Published: January 2014

Introduction:

Glucose test strips vary slightly from batch to batch. These variations are accounted for by a batch-specific “code”: A set of parameters defining the relationship between the signal change induced on the glucose test strip and the blood glucose concentration.

Methods:

We assessed the impact on accuracy of miscoding the ACCU-CHEK® Aviva system across a wide range of glucose test strip batches and glucose levels, throughout the shelf life of the glucose test strips.

Results:

The deviations in coding that we investigated had no effect on clinical action. Additionally, we showed, with mathematical modeling of a worst-case scenario, that the probability of an error altering clinical action is low. The batch-specific code of glucose test strips ensures the accuracy and safety of each blood glucose measurement. In addition to the parameters directly related to the blood glucose measurement, the electronic code chip contains the expiration date of the test strips and can deliver firmware updates for upgrades to the glucose meter.

Conclusions:

We eliminated the handling step of coding and retained all the advantages of coding. In Roche's newest all-in-one glucose meter, the ACCU-CHEK Compact Plus system, the batch-specific code is integrated into the drum that contains the glucose test strips. As a result, changing the drum containing the glucose test strips automatically changes the glucose test strip code. Patients with diabetes who use the ACCU-CHEK Compact Plus glucose meter do not have to be concerned with coding.
Miscoding and other User Errors: Importance of Ongoing Education for Proper Blood Glucose Monitoring Procedures
Authors: Schrock Linda E.
Published: January 2014

Background:

This article reviews the literature to date and reports on a new study that documented the frequency of manual code-requiring blood glucose (BG) meters that were miscoded at the time of the patient's initial appointment in a hospital-based outpatient diabetes education program.

Method:

Between January 1 and May 31, 2007, the type of BG meter and the accuracy of the patient's meter code (if required) and procedure for checking BG were checked during the initial appointment with the outpatient diabetes educator. If indicated, reeducation regarding the procedure for the BG meter code entry and/or BG test was provided.

Results:

Of the 65 patients who brought their meter requiring manual entry of a code number or code chip to the initial appointment, 16 (25%) were miscoded at the time of the appointment. Two additional problems, one of dead batteries and one of improperly stored test strips, were identified and corrected at the first appointment.

Conclusions:

These findings underscore the importance of checking the patient's BG meter code (if required) and procedure for testing BG at each encounter with a health care professional or providing the patient with a meter that does not require manual entry of a code number or chip to match the container of test strips (i.e., an autocode meter).
Use of Case-Based Reasoning to Enhance Intensive Management of Patients on Insulin Pump Therapy
Authors: Schwartz Frank L. , Shubrook Jay H. , Marling Cynthia R.
Published: January 2014

Background:

This study was conducted to develop case-based decision support software to improve glucose control in patients with type 1 diabetes mellitus (T1DM) on insulin pump therapy. While the benefits of good glucose control are well known, achieving and maintaining good glucose control remains a difficult task. Case-based decision support software may assist by recalling past problems in glucose control and their associated therapeutic adjustments.

Methods:

Twenty patients with T1DM on insulin pumps were enrolled in a 6-week study. Subjects performed self-glucose monitoring and provided daily logs via the Internet, tracking insulin dosages, work, sleep, exercise, meals, stress, illness, menstrual cycles, infusion set changes, pump problems, hypoglycemic episodes, and other events. Subjects wore a continuous glucose monitoring system at weeks 1, 3, and 6. Clinical data were interpreted by physicians, who explained the relationship between life events and observed glucose patterns as well as treatment rationales to knowledge engineers. Knowledge engineers built a prototypical system that contained cases of problems in glucose control together with their associated solutions.

Results:

Twelve patients completed the study. Fifty cases of clinical problems and solutions were developed and stored in a case base. The prototypical system detected 12 distinct types of clinical problems. It displayed the stored problems that are most similar to the problems detected, and offered learned solutions as decision support to the physician.

Conclusions:

This software can screen large volumes of clinical data and glucose levels from patients with T1DM, identify clinical problems, and offer solutions. It has potential application in managing all forms of diabetes.
Statistical Hypoglycemia Prediction
Authors: Cameron Fraser , Niemeyer Günter , Gundy-Burlet Karen , Buckingham Bruce
Published: January 2014

Background:

Hypoglycemia presents a significant risk for patients with insulin-dependent diabetes mellitus. We propose a predictive hypoglycemia detection algorithm that uses continuous glucose monitor (CGM) data with explicit certainty measures to enable early corrective action.

Method:

The algorithm uses multiple statistical linear predictions with regression windows between 5 and 75 minutes and prediction horizons of 0 to 20 minutes. The regressions provide standard deviations, which are mapped to predictive error distributions using their averaged statistical correlation. These error distributions give confidence levels that the CGM reading will drop below a hypoglycemic threshold. An alarm is generated if the resultant probability of hypoglycemia from our predictions rises above an appropriate, user-settable value. This level trades off the positive predictive value against lead time and missed events.

Results:

The algorithm was evaluated using data from 26 inpatient admissions of Navigator® 1-minute readings obtained as part of a DirecNet study. CGM readings were postprocessed to remove dropouts and calibrate against finger stick measurements. With a confidence threshold set to provide alarms that correspond to hypoglycemic events 60% of the time, our results were (1) a 23-minute mean lead time, (2) false positives averaging a lowest blood glucose value of 97 mg/dl, and (3) no missed hypoglycemic events, as defined by CGM readings. Using linearly interpolated FreeStyle capillary glucose readings to define hypoglycemic events provided (1) the lead time was 17 minutes, (2) the lowest mean glucose with false alarms was 100 mg/dl, and (3) no hypoglycemic events were missed.

Conclusion:

Statistical linear prediction gives significant lead time before hypoglycemic events with an explicit, tunable trade-off between longer lead times and fewer missed events versus fewer false alarms.
Closed-Loop Control and Advisory Mode Evaluation of an Artificial Pancreatic β Cell: Use of Proportional-Integral-Derivative Equivalent Model-Based Controllers
Authors: Percival Matthew W. , Zisser Howard , Jovanovic Lois , Doyle Francis J.
Published: January 2014

Background:

Using currently available technology, it is possible to apply modern control theory to produce a closed-loop artificial β cell. Novel use of established control techniques would improve glycemic control, thereby reducing the complications of diabetes. Two popular controller structures, proportional-integral-derivative (PID) and model predictive control (MPC), are compared first in a theoretical sense and then in two applications.

Methods:

The Bergman model is transformed for use in a PID equivalent model-based controller. The internal model control (IMC) structure, which makes explicit use of the model, is compared with the PID controller structure in the transfer function domain. An MPC controller is then developed as an optimization problem with restrictions on its tuning parameters and is shown to be equivalent to an IMC controller. The controllers are tuned for equivalent performance and evaluated in a simulation study as a closed-loop controller and in an advisory mode scenario on retrospective clinical data.

Results:

Theoretical development shows conditions under which PID and MPC controllers produce equivalent output via IMC. The simulation study showed that the single tuning parameter for the equivalent controllers relates directly to the closed-loop speed of response and robustness, an important result considering system uncertainty. The risk metric allowed easy identification of instances of inadequate control. Results of the advisory mode simulation showed that suitable tuning produces consistently appropriate delivery recommendations.

Conclusion:

The conditions under which PID and MPC are equivalent have been derived. The MPC framework is more suitable given the extensions necessary for a fully closed-loop artificial β cell, such as consideration of controller constraints. Formulation of the control problem in risk space is attractive, as it explicitly addresses the asymmetry of the problem; this is done easily with MPC.
A Subcutaneous Insulin Pharmacokinetic Model for Computer Simulation in a Diabetes Decision Support Role: Model Structure and Parameter Identification
Authors: Wong Jason , Chase J. Geoffrey , Hann Christopher E. , Shaw Geoffrey M. , Lotz Thomas F. , Lin Jessica , Le Compte Aaron J.
Published: January 2014

Objective:

The goal of this study was to develop a unified physiological subcutaneous (SC) insulin absorption model for computer simulation in a clinical diabetes decision support role. The model must model the plasma insulin appearance of a wide range of current insulins, especially monomer insulin and insulin glargine, utilizing common chemical states and transport rates, where appropriate.

Methods:

A compartmental model was developed with 13 patient-specific model parameters covering six diverse insulin types [rapid-acting, regular, neutral protamine Hagedorn (NPH), lente, ultralente, and glargine insulin]. Model parameters were identified using 37 sets of mean plasma insulin time-course data from an extensive literature review via nonlinear optimization methods.

Results:

All fitted parameters have a coefficient of variation <100% (median 51.3%, 95th percentile 3.6–60.6%) and can be considered a posteriori identifiable.

Conclusion:

A model is presented to describe SC injected insulin appearance in plasma in a diabetes decision support role. Clinically current insulin types (monomeric insulin, regular insulin, NPH, insulin, and glargine) and older insulin types (lente and ultralente) are included in a unified framework that accounts for nonlinear concentration and dose dependency. Future work requires clinical validation using published pharmacokinetic studies.
Brave New Worlds: How Virtual Environments Can Augment Traditional Care in the Management of Diabetes
Authors: Watson Alice J. , Grant Richard W. , Bello Heather , Hoch Daniel B.
Published: January 2014

New technologies, such as online networking tools, offer innovative ways to engage patients in their diabetes care. Second Life (SL) is one such virtual world that allows patients to interact in a 3D environment with peers and healthcare providers. This article presents a framework that demonstrates how applications within SL can be constructed to meet the needs of patients with diabetes, allowing them to attend group visits, learn more about lifestyle changes, and foster a sense of support and emotional well-being. This experiential approach to education may prove more engaging, and therefore successful, than existing strategies. Addressing concerns relating to privacy and liability is a necessary first step to engage providers in this new approach to patient care.
A Review of Current Evidence with Continuous Glucose Monitoring in Patients with Diabetes
Authors: Block Christophe De , Manuel-y-Keenoy Begoña , Van Gaal Luc
Published: January 2014

Devices that measure glucose on a near-continuous basis may provide a better insight into glycemic profiles, allowing patients with diabetes to make therapeutic adjustments to improve metabolic control, thereby reducing the risk of diabetic complications. Motivated and technologically adept patients with brittle diabetes, hypoglycemia unawareness, diabetic pregnancy, or who use pumps might benefit.

Current evidence of continuous glucose monitoring (CGM) on health outcome in patients with diabetes is critically reviewed. No data are available on chronic complications or mortality. Therefore, surrogate endpoints need to be investigated, particularly HbA1c, number of hypo- and hyperglycemic episodes, time within normal, high, or low glucose concentrations, glycemic variability, and quality of life.

Randomized controlled trials (RCTs) using CGM in a retrospective way did not show metabolic improvement. In contrast, most RCTs applying real-time CGM showed a decrease in HbA1c, reduced glycemic variability, and a diminished number and length of hypo- and hyperglycemic events. Using accurate, real-time CGM devices improves quality of life by reducing the fear of unexpected hypoglycemic events. These beneficial effects were observed despite the fact that in most studies no clear treatment algorithm based on CGM results was provided to the patients. However, most trials were too short in duration, with a variable use of CGM, and were performed in small study samples.

In conclusion, real-time CGM systems can improve metabolic control, reduce hypoglycemic episodes, and improve quality of life. Whether this holds true for longer time periods and in the majority of patients remains to be proven. In the long term, CGM might help to reduce chronic diabetes complications and perhaps also mortality, thereby reducing health care costs.
Insulin Delivery Route for the Artificial Pancreas: Subcutaneous, Intraperitoneal, or Intravenous? Pros and Cons
Authors: Renard Eric
Published: January 2014

Insulin delivery is a crucial component of a closed-loop system aiming at the development of an artificial pancreas. The intravenous route, which has been used in the bedside artificial pancreas model for 30 years, has clear advantages in terms of pharmacokinetics and pharmacodynamics, but cannot be used in any ambulatory system so far. Subcutaneous (SC) insulin infusion benefits from the broad expansion of insulin pump therapy that promoted the availability of constantly improving technology and fast-acting insulin analog use. However, persistent delays of insulin absorption and action, variability and shortterm stability of insulin infusion from SC-inserted catheters generate effectiveness and safety issues in view of an ambulatory, automated, glucose-controlled, artificial beta cell. Intraperitoneal insulin delivery, although still marginally used in diabetes care, may offer an interesting alternative because of its more-physiological plasma insulin profiles and sustained stability and reliability of insulin delivery.
The Benefits of Continuous Glucose Monitoring and a Glucose Monitoring Schedule in Individuals with Type 1 Diabetes during Recreational Diving
Authors: Adolfsson Peter , Örnhagen Hans , Jendle Johan
Published: January 2014

Background:

Our objective is to evaluate the Medtronic CGMS® continuous glucose monitoring system and plasma glucose (PG) measurement performed in a monitoring schedule as tools to identify individuals with type 1 diabetes at risk when diving.

Methods:

We studied 24 adults, 12 type 1 diabetes subjects and 12 controls, during 5 recreational scuba dives performed on 3 consecutive days. The CGMS was used by all participants on all the days and all the dives. Comparisons were made between PG performed in a monitoring schedule during the days of diving, self-monitored blood glucose (SMBG) performed 2 weeks prior to diving, and the CGMS during the study.

Results:

One hundred seventeen dives were performed. Hypoglycemia (<70 mg/dl) was found in six individuals and on nine occasions. However, no symptoms of hypoglycemia were present during or immediately postdiving. In one case, repetitive hypoglycemia prediving gave rise to a decision not to dive. None of the dives were aborted. The number of hypoglycemic episodes, 10 min prediving or immediately postdiving, were related to the duration of diabetes, r = 0.83 and p = 0.01, and the percentage of SMBG values below target (<72 mg/dl), r = 0.65 and p = 0.02. Moreover, the number of hypoglycemic episodes was also related to the total duration below low limit (<70 mg/dl), measured by the CGMS, r = 0.74 and p = 0.006.

Conclusion:

Safe dives are possible to achieve by well-informed, well-controlled individuals with type 1 diabetes. Using downloaded SMBG, CGMS, and repetitive PG in a monitoring schedule, it is possible to identify those subjects who are suitable for diving.
Telemedicine Process Used to Implement an Effective and Functional Screening Program for Diabetic Retinopathy
Authors: Wilson Robb R. , Silowash Russell , Anthony Leslie , Cecil R. Ann , Eller Andrew
Published: January 2014

Background:

Diabetic retinopathy, damage to the blood vessels in the retina, is the leading cause of blindness in adults 20–74 years of age. Nearly 300 million people worldwide have diabetes and nearly half of all people with diabetes will develop some degree of diabetic retinopathy during their lifetime. It has been estimated that blindness from diabetic retinopathy is preventable in at least 65% of cases, if detected early. The aim of the project was to develop a flexible, modular, mobile method for screening individuals that could be used effectively in a variety of medical and community settings.

Methods:

Our project created software to support a simple, effective retinal screening process for people with diabetes. The system included four separate software components: registration, imaging, grading, and tracking/reporting. The imaging component consisted of customized software running on a computer attached to a camera that drives retinal image acquisition.

Results:

Seven hundred and six subjects with diabetes were successfully consented, registered, imaged, and had their eye images graded. The mean time for subjects to be registered, imaged, and have eye images graded was 00:12:53. Seventy-six percent of the sample was instructed to follow-up with their eye doctor in 1 year (had no retinopathy or microaneurysms). Only six patients (0.8 %) were asked to see their eye doctor within 6 weeks (proliferative retinopathy or diabetic maculopathy).

Conclusion:

Our project successfully demonstrated that the retinal screening software and workflow process can be used to overcome challenges of providing adequate screening and diagnostic services for people at risk for diabetic retinopathy.
Performance Evaluation of a New Blood Glucose Monitor That Requires No Coding: The OneTouch® Vita™ System
Authors: Young Joanna K. , Ellison John M. , Marshall Robert
Published: January 2014

Background:

Improvements to blood glucose monitoring systems aim to simplify the testing process, reduce or eliminate errors, and provide additional information for patients with diabetes. New systems must continue to demonstrate high-quality analytical performance. The new OneTouch® Vita™ System (LifeScan, Inc., Milpitas, CA) offers a no-code testing process and proven technology found in the OneTouch® Ultra® System. Comparative studies were conducted with the new and established systems to evaluate their precision and accuracy.

Methods:

Within-run precision in blood, total precision with controls, and system accuracy were evaluated using three lots of OneTouch Vita Test Strips and one lot of OneTouch Ultra Test Strips. Accuracy was tested across a wide glucose range (38–520 mg/dl, 2.1–28.9 mmol/liter) using fingertip blood samples from 139 subjects. Reference plasma glucose values were obtained using the YSI 2300 STAT Plus Glucose & Lactate Analyzer (YSI Inc., Yellow Springs, OH). All studies were designed in accordance with requirements published by the International Organization for Standardization (ISO 15197).

Results:

Precision testing (within-run and total) with both systems produced coefficients of variation (CVs) of <5% for all sample types and glucose levels. Within-run precision testing with blood showed CVs of <3.1% and <4.7% for the OneTouch Vita and OneTouch Ultra Systems respectively. Total precision with control samples gave CVs of <3.0% and <3.6% for the two systems. Consensus error grid analysis showed equivalent clinical accuracy with 98.4% (821/834) and 98.2% (273/278) of results within zone A. Both systems met the ISO acceptability requirements for system accuracy.

Conclusion:

The OneTouch Vita System provides a simple no-code testing process with performance comparable to the OneTouch Ultra and OneTouch Ultra2 Systems.
An Analysis: To Code or Not to Code—That is the Question
Authors: Ginsberg Barry H.
Published: January 2014

Most blood glucose monitoring systems need coding to correct for variation in lots of enzyme, which leads to differences in lots of strips. About 16% of patients miscode the meters, although the magnitude of the miscoding is unstudied. This miscoding has the potential to cause errors as high as 30% and to cause errors in adjusting insulin therapy that could lead to hypoglycemia at least 10% of the time. Studies of these systems suggest that they have accuracy similar to other current meters and have similar physical characteristics. Because they do not require coding, they are often easier to use. No-coding systems have the potential to avoid some errors in blood glucose.
FreeStyle Mini™ Blood Glucose Results Are Accurate and Suitable for Use in Glycemic Clamp Protocols
Authors: Cohen Ohad , Shaklai Sigal , Gabis Ephraim , Pani Michael A.
Published: January 2014

Objective:

We assessed the accuracy of the FreeStyle Mini™ (FSM) meter for use in glycemic clamp and meal protocols in comparison with the HemoCue Glucose 201 DM Analyzer (HemoCue) and the YSI 2300 STAT Glucose Oxidase Analyzer (YSI).

Methods:

Seven volunteers with type 2 diabetes mellitus, 35–69 years old, underwent a frequently sampled meal test and a graded hyperglycemic test, on two separate days, with one of the volunteers undergoing each test twice. Samples for glucose measurements were obtained from arterialized venous blood. A total of 420 samples (with glucose levels ranging from 63 to 388 mg/dl) were available for comparison. On average, 10 measurements were available for every 5 mg/dl increment in glucose level in the range of 130–310 mg/dl. Blood glucose measurements were done on each sample with the FSM, HemoCue, and YSI.

Results:

FreeStyle Mini blood glucose values correlated closely with the YSI readings. Of the FSM measurements, 99.0% were within the Clarke error grid zone A; 51.3%, 84.7%, and 96.2% of the FSM readings were within 5%, 10% and 15% of the YSI values, respectively. The FSM was significantly more accurate than the HemoCue (84.7% vs 76.6% of results within 10% of the YSI results; p = .0038). The mean average relative difference of the FSM (5.8%) was also significantly lower than that of the HemoCue (6.8%; p = .0013)

Conclusions:

The FSM provides accurate results and constitutes a suitable alternative for bedside blood glucose measurements in experimental procedures, helping to reduce sample size, turnaround time, and cost.
Finger Pricking and Pain: A Never Ending Story
Authors: Heinemann Lutz
Published: January 2014

Without finger pricking, no self-measurement of blood glucose (SMBG) is possible. However, the number of scientific studies dealing with this topic, which is highly relevant for patients, is surprisingly small. This is in sharp contrast to the number of papers about blood glucose meters and SMBG in general. This article highlights a number of aspects that are relevant when it comes to finger pricking and pain. There is a clear improvement in the technology employed in the many different lancing devices that are on the market nowadays; however, no good head-to-head comparison study has been performed to date. The invention of novel devices for finger pricking will most likely bring more attention to this topic.
A Review of the Biocompatibility of Implantable Devices: Current Challenges to Overcome Foreign Body Response
Authors: Onuki Yoshinori , Bhardwaj Upkar , Papadimitrakopoulos Fotios , Burgess Diane J.
Published: January 2014

In recent years, a variety of devices (drug-eluting stents, artificial organs, biosensors, catheters, scaffolds for tissue engineering, heart valves, etc.) have been developed for implantation into patients. However, when such devices are implanted into the body, the body can react to these in a number of different ways. These reactions can result in an unexpected risk for patients. Therefore, it is important to assess and optimize the biocompatibility of implantable devices. To date, numerous strategies have been investigated to overcome body reactions induced by the implantation of devices. This review focuses on the foreign body response and the approaches that have been taken to overcome this. The biological response following device implantation and the methods for biocompatibility evaluation are summarized. Then the risks of implantable devices and the challenges to overcome these problems are introduced. Specifically, the challenges used to overcome the functional loss of glucose sensors, restenosis after stent implantation, and calcification induced by implantable devices are discussed.
Consensus Report of the Coalition for Clinical Research—Self-Monitoring of Blood Glucose
Authors: Klonoff David C. , Bergenstal Richard , Blonde Lawrence , Boren Suzanne Austin , Church Timothy S. , Gaffaney Jenifer , Jovanovič Lois , Kendall David M. , Kollman Craig , Kovatchev Boris P. , Leippert Claudia , Owens David R. , Polonsky William H. , Reach Gérard , Renard Eric , Riddell Michael C. , Rubin Richard R. , Schnell Oliver , Siminiero Linda M. , Vigersky Robert A. , Wilson Darrell M. , Wollitzer Alison Okada
Published: January 2014

The Coalition for Clinical Research—Self-Monitoring of Blood Glucose Scientific Board, a group of nine academic clinicians and scientists from the United States and Europe, convened in San Francisco, California, on June 11–12, 2008, to discuss the appropriate uses of self-monitoring of blood glucose (SMBG) and the measures necessary to accurately assess the potential benefit of this practice in noninsulin-treated type 2 diabetes mellitus (T2DM). Thirteen consultants from the United States, Europe, and Canada from academia, practice, and government also participated and contributed based on their fields of expertise. These experts represent a range of disciplines that include adult endocrinology, pediatric endocrinology, health education, mathematics, statistics, psychology, nutrition, exercise physiology, and nursing. This coalition was organized by Diabetes Technology Management, Inc. Among the participants, there was consensus that:

protocols assessing the performance of SMBG in noninsulin treated T2DM must provide the SMBG intervention subjects with blood glucose (BG) goals and instructions on how to respond to BG data in randomized controlled trials (RCTs); intervention subjects in clinical trials of SMBG-driven interventions must aggressively titrate their therapeutic responses or lifestyle changes in response to hyperglycemia; control subjects in clinical trials of SMBG must be isolated from SMBG-driven interventions and not be contaminated by physician experience with study subjects receiving a SMBG intervention; the best endpoints to measure in a clinical trial of SMBG in T2DM include delta Hemoglobin A1c levels, hyperglycemic events, hypoglycemic events, time to titrate noninsulin therapy to a maximum necessary dosage, and quality of life indices; either individual randomization or cluster randomization may be appropriate methods for separating control subjects from SMBG intervention subjects, provided that precautions are taken to avoid bias and that the sample size is adequate; treatment algorithms for assessing SMBG in T2DM may include a dietary, exercise, and/or medication intervention, which are all titratable according to the SMBG values; the medical literature contains very little information about the performance of SMBG in T2DM from RCTs in which treatment algorithms were used for dysglycemic values; and research on the performance of SMBG in T2DM based on sound scientific principles and clinical practices is needed at this time.
Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Spray (Nasulin™) Administered to Healthy Male Volunteers: Influence of the Nasal Cycle
Authors: Leary Andrew C. , Dowling Muiris , Cussen Kathleen , O'Brien Jackie , Stote Robert M.
Published: January 2014

Background:

The pharmacokinetics and pharmacodynamics of a Bentley Pharmaceuticals proprietary intranasal (IN) insulin formulation (Nasulin™) were studied in healthy volunteers.

Methods:

Thirteen fasting healthy male volunteers received five doses of medication (one dose of 4 international units [IU] subcutaneous (SC) regular insulin and four doses of 25 IU IN insulin) at least 48 h apart. Serum insulin, serum C-peptide, and plasma glucose were measured in the 4 h after dosing. Profiles were compared for IN insulin spray following administration into the dominant nostril (more open at time of dosing) and into the nondominant nostril (less open at time of dosing).

Results:

The formulation was generally well tolerated. A rise in serum insulin levels accompanied by a decrease in plasma glucose was seen following all doses. For IN doses, peak insulin levels were generally attained in 10–20 min and remained elevated for approximately 40–50 min; the resultant effect on glucose peaked at 40 min and waned approximately 2 h postdosing. As reported in other studies, the interindividual response to insulin was variable. The comparative absorption of IN insulin relative to SC insulin was 12.0% (dominant nostril) or 15.4% (nondominant nostril) over 2 h. This increased somewhat if sneezers and volunteers with moderately blocked nostrils were removed from the analysis.

Conclusions:

This IN formulation was generally well tolerated and relatively well absorbed. While both insulin data (maximal plasma concentration and area under the plasma concentration time curve) and glucose data (% fall) support a trend toward better absorption from the nondominant nostril, this did not reach statistical significance. Nasulin can be administered without reference to the nasal cycle.
Glycemic Variability: The Third Component of the Dysglycemia in Diabetes. Is it Important? How to Measure it?
Authors: Monnier Louis , Colette Claude , Owens David R.
Published: January 2014

The dysglycemia of diabetes includes two components: (1) sustained chronic hyperglycemia that exerts its effects through both excessive protein glycation and activation of oxidative stress and (2) acute glucose fluctuations. Glycemic variability seems to have more deleterious effects than sustained hyperglycemia in the development of diabetic complications as both upward (postprandial glucose increments) and downward (interprandial glucose decrements) changes activate the oxidative stress. For instance, the urinary excretion rate of 8-iso-PGF2α, a reliable marker of oxidative stress, was found to be strongly, positively correlated ( r = 0.86, p < .001) with glycemic variability assessed from the mean amplitude of glycemic excursions (MAGE) as estimated by continuous glucose monitoring systems (CGMS). These observations therefore raise the question of whether we have the appropriate tools for assessing glycemic variability in clinical practice. From a statistical point of view, the standard deviation (SD) around the mean glucose value appears as the “gold standard.” By contrast, the MAGE index is probably more appropriate for selecting the major glucose swings that are calculated as the arithmetic mean of differences between consecutive peaks and nadirs, provided that the differences be greater than the SD around the mean values. Furthermore, calculating the MAGE index requires continuous glucose monitoring, which has the advantage to detect all isolated upward and downward acute glucose fluctuations. In conclusion, the increasing use of CGMSs will certainly promote better assessment and management of glycemic variability.
United States Patient Preference and Usability for the New Disposable Insulin Device Solostar® versus other Disposable Pens
Authors: Fischer Jerome S. , Edelman Steven V. , Schwartz Sherwyn L.
Published: January 2014

The uptake of insulin pen use has been slow in the United States, despite their advantages over the vial/syringe. We present results of a United States subset of 150 patients with type 1/type 2 diabetes, who were enrolled in an open-label study, that assessed usability, pen features, and patient preferences for four prefilled insulin pens: SoloSTAR®, FlexPen®, Lilly disposable pen, and a prototype, Pen X. Overall, the SoloSTAR and FlexPen were more user-friendly; 95 and 88% of patients, respectively, completed the steps correctly (without safety/attach-needle step—deemed independent of device) versus the Lilly disposable pen (60%) and Pen X (61%; all p < 0.05). The SoloSTAR was rated highest most frequently for pen feature comparisons. Results suggest that the SoloSTAR and FlexPen could potentially facilitate insulin use in the United States.
The Median is Not the Only Message: A Clinician's Perspective on Mathematical Analysis of Glycemic Variability and Modeling in Diabetes Mellitus
Authors: McCall Anthony L. , Kovatchev Boris P.
Published: January 2014

Hemoglobin A1c (HbA1c), a long-term, integrated average of tissue exposure to hyperglycemia, is the best reflection of average glucose concentrations and the best proven predictor of microvascular complications of diabetes mellitus. However, HbA1c fails to capture glycemic variability and the risks associated with extremes of hypoglycemia and hyperglycemia.

These risks are the primary barrier to achieving the level of average glucose control that will minimize both the microvascular and the long-term macrovascular complications of type 1 diabetes. High blood glucose levels largely due to prandial excursions produce oxidative and inflammatory stress with potential acceleration of preexisting atherosclerosis and increased cardiovascular risk. Moreover, some temporal aspects of glycemic variation, including the rates of rise and fall of glucose, are associated with adverse cognitive and mood symptoms in those with diabetes.

Methods to quantify the risk of glycemic extremes, both high and low, and the variability including its temporal aspects are now more precise than ever. These important endpoints should be included for use in clinical trials as useful metrics and recognized by regulatory agencies, which has not been the case in the past. Precise evaluation of glycemic variability and its attendant risks are essential in the design of optimal therapies; for these reasons, inclusion of these metrics and the pulsatile hormone patterns in mathematical models may be essential. For the clinician, the incursion of mathematical models that simulate normal and pathophysiological mechanisms of glycemic control is a reality and should be also gradually incorporated into clinical practice.