bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical Approach of Assessing the Reliability of Glucose Sensors: The GLYCENSIT Procedure
Authors: Van Herpe Tom , Pelckmans Kristiaan , De Brabanter Jos , Janssens Frizo , De Moor Bart , Van den Berghe Greet
Published: January 2014

Background:

In healthcare, patients with diabetes are instructed on how to apply intensified insulin therapy in an optimal manner. Tight blood glucose control is also performed on patients treated in the intensive care unit (ICU). Different blood glucose meters and glucose monitoring systems (GMSs) are used to achieve this goal, and some may lack reliability.

Methods:

The GLYCENSIT procedure is a statistical assessment tool we are proposing for evaluating the significant difference of paired glucose measurements. The performance of the GlucoDay® system in the ICU is analyzed with GLYCENSIT.

Results:

The GLYCENSIT analysis comprises three phases: testing possible persistent measurement behavior as a function of the glycemic range, testing the number of measurement errors with respect to a standard criterion for binary assessment of glucose sensors, and computing the tolerance intervals that indicate possible test sensor deviations for new observations. The probability of the tolerance intervals directly reflects the number of samples and additionally improves current assessment techniques. The method can be tuned according to the clinician's preferences regarding significance level, tolerance level, and glycemic range cutoff values. The measurement behavior of the GlucoDay sensor is found to be persistent but inaccurate and returns wide tolerance intervals, suggesting that the GlucoDay sensor may not be sufficiently reliable for glycemia control in the ICU.

Conclusions:

The GLYCENSIT procedure aims to serve as statistical guide for clinicians in the assessment of glucose sensor devices.
Evaluation of Implementation of a Fully Automated Algorithm (Enhanced Model Predictive Control) in an Interacting Infusion Pump System for Establishment of Tight Glycemic Control in Medical Intensive Care Unit Patients
Authors: Kulnik Roman , Plank Johannes , Pachler Christoph , Wilinska Malgorzata E. , Groselj-Strele Andrea , Röthlein Doris , Wufka Matthias , Kachel Norman , Smolle Karl Heinz , Perl Sabine , Pieber Thomas Rudolf , Hovorka Roman , Ellmerer Martin
Published: January 2014

Background:

The objective of this study was to investigate the performance of a newly developed decision support system for the establishment of tight glycemic control in medical intensive care unit (ICU) patients for a period of 72 hours.

Methods:

This was a single-center, open, non-controlled feasibility trial including 10 mechanically ventilated ICU patients. The CS-1 decision support system (interacting infusion pumps with integrated enhanced model predictive control algorithm and user interface) was used to adjust the infusion rate of administered insulin to normalize blood glucose. Efficacy and safety were assessed by calculating the percentage of values within the target range (80–110 mg/dl), hyperglycemic index, mean glucose, and hypoglycemic episodes (<40 mg/dl).

Results:

The percentage of values in time in target was 47.0% (±13.0). The average blood glucose concentration and hyperglycemic index were 109 mg/dl (±13) and 10 mg/dl (±9), respectively. No hypoglycemic episode (<40 mg/dl) was detected. Eleven times (1.5% of all given advice) the nurses did not follow and, thus, overruled the advice of the CS-1 system. Several technical malfunctions of the device (repetitive error messages and missing data in the data log) due to communication problems between the new hardware components are shortcomings of the present version of the device. As a consequence of these technical failures of system integration, treatment had to be stopped ahead of schedule in three patients.

Conclusions:

Despite technical malfunctions, the performance of this prototype CS-1 decision support system was, from a clinical point of view, already effective in maintaining tight glycemic control. Accordingly, and with technical improvement required, the CS-1 system has the capacity to serve as a reliable tool for routine establishment of glycemic control in ICU patients.
Group of Signs: A New Method to Evaluate Glycemic Variability
Authors: Zaccardi Francesco , Di Stefano Paola , Busetto Elena , Federici Marco Orsini , Manto Andrea , Infusino Fabio , Lanza Gaetano Antonio , Pitocco Dario , Ghirlanda Giovanni
Published: January 2014

Background:

Glycemic variability is an important parameter used to resolve potential clinical problems in diabetic patients. It is known that glycemic variability generates oxidative stress and potentially contributes to the development of macro- and microvascular complications in diabetes. By controlling glycemic variability, it is possible to reduce these complications and to set the therapy for all patients with diabetes. The aims of this study were to (1) propose a new standardized, objective, and flexible approach to measure glycemic variability by a continuous glucose monitoring system (CGMS)—the group of signs (GOS) method; (2) compare the correlation between mean amplitude of glucose excursion (MAGE), a well-known index of glycemic variability calculated by the physician and the MAGE defined with the GOS method, in order to validate the GOS; and (3) suggest new indexes of glycemic variability.

Methods:

We tested the GOS algorithm on data collected by a CGMS every 5 minutes for 24 hours on 50 patients. Consequently, for 8 patients we calculated and compared the physician's MAGE in the standard way and by the GOS method.

Results:

Comparison between the two methods has shown high correlations, from a minimum correlation of 86% to a maximum of 98%, with p values <0.01 (Pearson test).

Conclusions:

Preliminary data suggest that the proposed algorithm is a valid, efficient, and reliable method able to calculate the standard MAGE on CGMS data systematically and to create other alternative glycemic variability indexes.
Hemorheological Disorders in Diabetes Mellitus
Authors: Cho Young I. , Mooney Michael P. , Cho Daniel J.
Published: January 2014

The objective of the present study is to review hemorheological disorders in diabetes mellitus. Several key hemorheological parameters, such as whole blood viscosity, erythrocyte deformability, and aggregation, are examined in the context of elevated blood glucose level in diabetes. The erythrocyte deformability is reduced, whereas its aggregation increases, both of which make whole blood more viscous compared to healthy individuals. The present paper explains how the increased blood viscosity adversely affects the microcirculation in diabetes, leading to microangiopathy.
Patch-Pump Technology to Manage Type 2 Diabetes Mellitus: Hurdles to Market Acceptance
Authors: Skladany Matthew J. , Miller Michaela , Guthermann Joshua S. , Ludwig Christopher R.
Published: January 2014

The recent development of novel “patch”-type insulin infusion pump (IIP) technologies has created an opportunity to improve the quality of life for a broader type 2 diabetes patient demographic. At first glance, type 2 diabetes patients represent a large percentage of the total diabetes patient population; however, adoption of traditional IIP products and multiple daily injection (MDI) therapy has remained limited amongst this patient segment. With an insulin reservoir, delivery system, and cannula integrated into a small, wearable, disposable or semidisposable device, patch pumps simplify traditional IIP therapy, while potentially offering therapeutic benefits over traditional MDI therapy. Herein, potential benefits of patch-pump technology for type 2 diabetes patients are considered while outlining the hurdles to broad product adoption that will likely limit the near term commercial opportunity.
System-Level Control to Optimize Glucagon Counterregulation by Switch-Off of α-Cell Suppressing Signals in β-Cell Deficiency
Authors: Farhy Leon S. , McCall Anthony L.
Published: January 2014

Background:

Glucagon counterregulation (GCR) is a key protection against hypoglycemia that is compromised in diabetes. In β-cell-deficient rats, GCR pulsatility can be amplified if insulin (INS) or somatostatin (SS) are infused in the pancreatic artery and then switched off during hypoglycemia. The data indicate that these signals act by different mechanisms, and here we analyze the differences between the two switch offs (SOs) and predict the GCR-amplifying effect of their individual or combined application.

Methods:

A minimal control network (MCN) of α/δ-cell interactions is approximated by differential equations to explain the GCR response to a SO and test in silico the hypotheses: (i) INS SO suppresses basal and pulsatile, while SS SO blocks only pulsatile glucagon release and (ii) simultaneous application of the two switch offs will augment the individual GCR response.

Results:

The mechanism postulated in (i) explains the differences in the GCR responses between the SOs. The MCN predicts that simultaneous application of INS and SS decreases basal glucagon but increases post-SO amplitude, thus doubling the response of GCR achieved by each of the individual signals.

Conclusion:

The current analyses predict that INS and SS SOs improve defective GCR in β-cell deficiency through different but complementary mechanisms and suggest SO strategies to maximally enhance GCR in type 1 diabetes by simultaneous manipulation of the network control. These results are clinically relevant, as they could have application to design of an artificial pancreas by providing ways to augment GCR that would not require glucagon infusion.
Physical Activity into the Meal Glucose—Insulin Model of Type 1 Diabetes: In Silico Studies
Authors: Dalla Man Chiara , Breton Marc D. , Cobelli Claudio
Published: January 2014

Introduction:

A simulation model of a glucose—insulin system accounting for physical activity is needed to reliably simulate normal life conditions, thus accelerating the development of an artificial pancreas. In fact, exercise causes a transient increase of insulin action and may lead to hypoglycemia. However, physical activity is difficult to model. In the past, it was described indirectly as a rise in insulin. Recently, a new parsimonious model of exercise effect on glucose homeostasis has been proposed that links the change in insulin action and glucose effectiveness to heart rate (HR). The aim of this study was to plug this exercise model into our recently proposed large-scale simulation model of glucose metabolism in type 1 diabetes to better describe normal life conditions.

Methods:

The exercise model describes changes in glucose—insulin dynamics in two phases: a rapid on-and-off change in insulin-independent glucose clearance and a rapid-on/slow-off change in insulin sensitivity. Three candidate models of glucose effectiveness and insulin sensitivity as a function of HR have been considered, both during exercise and recovery after exercise. By incorporating these three models into the type 1 diabetes model, we simulated different levels (from mild to moderate) and duration of exercise (15 and 30 minutes), both in steady-state (e.g., during euglycemic—hyperinsulinemic clamp) and in nonsteady state (e.g., after a meal) conditions.

Results:

One candidate exercise model was selected as the most reliable.

Conclusions:

A type 1 diabetes model also describing physical activity is proposed. The model represents a step forward to accurately describe glucose homeostasis in normal life conditions; however, further studies are needed to validate it against data.
Medical Implications of Obesity in Horses—Lessons for Human Obesity
Authors: Johnson Philip J. , Wiedmeyer Charles E. , Messer Nat T. , Ganjam Venkataseshu K.
Published: January 2014

There is growing recognition that obesity is common and represents a significant detriment to the health of companion animals in a manner similar to that by which it is affecting the human population. As is the case for other species, obesity appears to promote insulin resistance in horses and it is through this pathophysiological process that many of the adverse medical consequences of obesity are being characterized. Equine medical conditions that have been described in the context of obesity and insulin resistance differ from those in humans. Chronic human conditions that have been attributed to obesity and insulin resistance, such as atherosclerosis and diabetes mellitus, are rarely described in obese horses. Significant current interest is centered on the recognition that insulin resistance plays a role in the pathogenesis of laminitis, a potentially severe and debilitating cause of lameness in the equine species. Other equine medical conditions that are more likely in obese, insulin-resistant individuals include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's syndrome) represents another common endocrinopathic condition of older horses associated with insulin resistance. This review presents an introductory overview of the present understanding of obesity and insulin resistance and how these conditions may be associated with disease conditions in horses.
Maggot Therapy Takes Us Back to the Future of Wound Care: New and Improved Maggot Therapy for the 21st Century
Authors: Sherman Ronald A.
Published: January 2014

In the 21st century, eighty years after William Baer presented his groundbreaking work treating bone and soft tissue infections with live maggots, thousands of therapists around the globe have rediscovered the benefits of maggot therapy. The renaissance in maggot therapy is due in large part to recent technological advancements that have solved or minimized many of the treatment's earlier drawbacks: the need for reliable access to this perishable medical device, simplified application, and low-cost production. Modern dressing materials have simplified the procedure and minimized the risk of escaping maggots. The establishment of dozens of laboratories throughout the world, along with access to overnight courier services in many regions, has made medicinal maggots readily available to millions of people in need. Studies show that fears of patient nonacceptance are unfounded. The medical literature is rapidly growing with scientific evidence demonstrating the efficacy and safety of maggot therapy for a variety of problematic wounds. This article examines how these and other technologies are optimizing the study and application of maggot therapy for wound care.
Insulin Pump Safety Meeting: Summary Report
Authors: Klonoff David C. , Reyes Juliet S.
Published: January 2014

Diabetes Technology Society convened a panel of insulin pump experts in Bethesda, Maryland, on November 12, 2008, at the request of the Food and Drug Administration. The group consisted of physicians, nurses, diabetes educators, and engineers from across the United States. The panel members (1) discussed safety features of insulin pump therapy and (2) recommended adjustments to current insulin pump design and use to enhance overall safety. Software and hardware features of insulin pumps were analyzed from engineering, medical, nursing, and pump-user perspectives. The meeting was divided into four sections: (1) Engineering Safety—Designing Software and Hardware for Insulin Pump Therapy; (2) Patient Safety—Selecting Patients and Clinical Settings for Insulin Pump Use; (3) Clinical Safety—Determining and Delivering Insulin Dosages Using Insulin Pump Therapy; and (4) Personal Experiences—A Panel Discussion about Insulin Pump Safety. Six aspects of insulin pump technology were noted to present potential safety problems: (1) software, (2) wireless communication, (3) hardware, (4) alarms, (5) human factors, and (6) bolus-dose calculation. There was consensus among meeting participants that insulin pump therapy is beneficial in patients of all ages and that insulin pump safety must be assured through careful regulation.
A Review of the Challenge in Measuring Hemoglobin A1c
Authors: Weykamp Cas , John W. Garry , Mosca Andrea
Published: January 2014

The attraction of the simple biochemical concept combined with a clinical requirement for a long-term marker of glycolic control in diabetes has made hemoglobin A1c (HbA1c) one of the most important assays undertaken in the medical laboratory. The diversity in the biochemistry of glycation, clinical requirements, and management demands has resulted in a broad range of methods being developed since HbA1c was described in the late 1960s. A range of analytic principles are used for the measurement of HbA1c. The charge difference between hemoglobin A0 and HbA1c has been widely utilized to separate these two fractions, most notably found these days in ion-exchange high-performance liquid chromatography systems; the difference in molecular structure (affinity chromatography and immunochemical methods) are becoming widely available. Different results found in different laboratories using a variety of HbA1c analyses resulted in the need for standardization, most notably in the United States, Japan, and Sweden. Designated comparison methods are now located in these three countries, but as they are arbitrarily chosen and have differences in specificity, results of these methods and the reference values and action limits of the methods differ and only harmonized HbA1c in specific geographic areas. A reference measurement system within the concept of metrological traceability is now globally accepted as the only valid analytic anchor. However, there is still discussion over the units to be reported. The consensus statement of the International Federation of Clinical Chemistry (IFCC), the American Diabetes Association, the International Diabetes Federation, and the European Association for the Study of Diabetes suggests reporting HbA1c in IFCC units (mmol/mol), National Glycohemoglobin Standardization Program units (%), and estimated average glucose (either in mg/dl or mmol/liter). The implementation of this consensus statement raised new questions, to be answered in a concerted action of clinicians, biochemists, external quality assessment organizers, patient groups, and manufacturers.
Prescription Checking Device Promises to Resolve Intractable Hypoglycemia
Authors: Albisser A. Michael , Alejandro Rodolfo , Sperlich Marianne , Ricordi Camillo
Published: January 2014

Background:

Satisfactory glycemic control, meeting American Diabetes Association recommendations, is often accompanied by unsatisfactory hypoglycemia. The converse is also true. We hypothesize that this diabetes treatment dilemma may be resolved by repeated, objective, prescription checks. To do this, a new, two-part device has been developed. It includes a personal diabetes database for the patient and a built-in diabetes prescription checker for the provider. Its goals are to enhance diabetes education and improve patient care.

Research Design and Methods:

The device includes a database and supporting software, all contained in a standard USB flash drive. Using the medical prescription, body weight, and recent self-monitored blood glucose (SMBG) data, prescription checks can be done at any time. To demonstrate the device's capabilities, an observational study was performed using data from 11 patients with type 1 diabetes mellitus, on intensified therapy, with a mean glycated hemoglobin A1c <7%, and who all suffered intractable hypoglycemia. Patients had performed SMBG contours on successive days at monthly intervals. Each contour included pre- and postmeal as well as bedtime measurements. The replicated contours were used to predict the patient's glycemic profile each month. Applying a built-in simulator to each profile, changes in the prescription were explored that were consistent with reducing the recalcitrant hypoglycemia.

Results:

A total of 110 glycemic profiles containing 822 profile points were explored. Of these profile points, 351 (43%) showed risks of hypoglycemia, whereas 385 (47%) fell outside desired ranges. With the simulated changes in the prescription, the predicted risks of hypoglycemia were reduced 2.5-fold with insignificant increases predicted in hemoglobin A1c levels of +0.6 ± 0.9%.

Conclusions:

Anovel support tool for diabetes promises to resolve the diabetes treatment dilemma. Supporting the patient, it improves self-management. Supporting the provider, it reviews the medical prescription in light of objective outcomes and formalizes interventions for maximum safety and efficacy.
Safety Constraints in an Artificial Pancreatic β Cell: An Implementation of Model Predictive Control with Insulin on Board
Authors: Ellingsen Christian , Dassau Eyal , Zisser Howard , Grosman Benyamin , Percival Matthew W. , Jovanovič Lois , Doyle Francis J.
Published: January 2014

Background:

Type 1 diabetes mellitus (T1DM) is characterized by the destruction of pancreatic β cells, resulting in the inability to produce sufficient insulin to maintain normoglycemia. As a result, people with T1DM depend on exogenous insulin that is given either by multiple daily injections or by an insulin pump to control their blood glucose. A challenging task is to design the next step in T1DM therapy: a fully automated insulin delivery system consisting of an artificial pancreatic β cell that shall provide both safe and effective therapy. The core of such a system is a control algorithm that calculates the insulin dose based on automated glucose measurements.

Methods:

A model predictive control (MPC) algorithm was designed to control glycemia by controlling exogenous insulin delivery. The MPC algorithm contained a dynamic safety constraint, insulin on board (IOB), which incorporated the clinical values of correction factor and insulin-to-carbohydrate ratio along with estimated insulin action decay curves as part of the optimal control solution.

Results:

The results emphasized the ability of the IOB constraint to significantly improve the glucose/insulin control trajectories in the presence of aggressive control actions. The simulation results indicated that 50% of the simulations conducted without the IOB constraint resulted in hypoglycemic events, compared to 10% of the simulations that included the IOB constraint.

Conclusions:

Achieving both efficacy and safety in an artificial pancreatic β cell calls for an IOB safety constraint that is able to override aggressive control moves (large insulin doses), thereby minimizing the risk of hypoglycemia.
Oral Insulin: The Rationale for This Approach and Current Developments
Authors: Arbit Ehud , Kidron Miriam
Published: January 2014

Insulin remains the most effective and durable hypoglycemic agent for the treatment of diabetes. The addition of an effective oral insulin dosage form to the antidiabetes armamentarium may have significant benefits in terms of fostering compliance and adherence among patients, as well as physiologic advantages due to the fact that such a dosage form replicates the natural route of insulin secretion and absorption through the portal vein and targets the liver directly. Several companies have developed technological platforms that protect polypeptides and proteins from enzymatic hydrolysis, enable their transport across the epithelial lining, and promote their absorption from the gastrointestinal tract. A review of the potential physiological rationale and advantages, as well as of current pertinent technologies used specifically with insulin, is herewith provided.
Biologic Variability in Plasma Glucose, Hemoglobin A1c, and Advanced Glycation End Products Associated with Diabetes Complications
Authors: Leslie R. David G. , Cohen Robert M.
Published: January 2014

Plasma glucose plays a key role in the complications of diabetes mellitus. Hemoglobin A1c (HbA1c) and circulating concentrations of advanced glycation end products (AGEs) are central to diabetes clinical care and pathophysiology. However, there is evidence for variation between individuals in the relationship of plasma glucose to both these measures and to specific complications. The glycation gap (GG) and hemoglobin glycation index represent tools for quantitating the variability in the relationship between plasma glucose and HbA1c useful for identification of underlying mechanisms. Recent evidence demonstrates the heritability of HbA1c, the GG, and AGEs, yet not of glycated serum proteins. There has been tremendous effort devoted to identifying the heritable basis of types 1 and 2 diabetes; however, studies on the heritable contributors to these mediators of glucose effect on complications are only beginning. New evidence for normal biologic variation in the distribution of glucose into the red blood cell (RBC) intracellular compartment and RBC lifespan in people with and without diabetes represent candidates for heritable mechanisms and contributors to the rise in HbA1c with age. Taken as a whole, genetic and mechanistic evidence suggests new potential targets for complications prevention and improvement in complications risk estimation. These observations could help tilt the risk—benefit balance in glycemic control toward a more beneficial outcome.
Detecting Undiagnosed Type 2 Diabetes: Family History as a Risk Factor and Screening Tool
Authors: Valdez Rodolfo
Published: January 2014

A family history of diabetes is a major risk factor for the disease. As such, it is often included in a variety of tools designed to detect either people at risk of diabetes or people with undiagnosed diabetes. One of the reasons to screen for diabetes is that it has a prolonged asymptomatic phase, which includes impaired fasting glucose, impaired glucose tolerance, and the early stages of diabetes. In terms of prevalence, diabetes is a major public health problem. Evidence shows that the detection of impaired glucose metabolism in its early stages (prediabetes) could lead to the delay or prevention of the disease and its complications. However, the issue of using family history to screen for diabetes must be discussed within the context of screening for diabetes in general. Screening for a disease among asymptomatic people must meet a series of stringent requirements to ensure the best possible outcomes. Screening for diabetes meets most of these requirements but the ones it does not meet are still important. Therefore, based on systematically collected evidence or simply by consensus among scientists, influential organizations recommend screening only among high-risk individuals. As a result, researchers have developed a variety of simple tools to identify high-risk individuals for diabetes in populations. Family history is included as a key variable in the vast majority of them. This article is a brief overview of the reasons to screen for diabetes in general, the tools available for conducting this screening, and the role of family history in these tools.
The Prevention of Type 2 Diabetes: An Overview
Authors: Marrero David G.
Published: January 2014

Type 2 diabetes mellitus is one of the major public health threats in the United States today, reaching epidemic rates. Epidemiological evidence suggests a strong link between obesity and the risk of developing diabetes. Increasing evidence demonstrates that lifestyle interventions can significantly delay or possibly prevent the onset of type 2 diabetes in persons with increased risk. Despite these findings, there remain important barriers to the translation of this research to the public health. These include identifying persons with an increased risk for developing the disease and the lack of easily accessible, cost-effective intervention programs. At least one study, however, has effectively implemented an evidenced-based intervention in community settings, suggesting that it may be possible to develop a model for the national scalability of primary prevention in the United States.
Comparison of Lancing Devices for Self-Monitoring of Blood Glucose regarding Lancing Pain
Authors: Kocher Serge , Tshiananga J. K. Tshiang , Koubek Richard
Published: January 2014

Background:

Self-monitoring of blood glucose empowers diabetes patients to effectively control their blood glucose (BG) levels. A potential barrier to frequent BG controls is lancing pain, intrinsically linked to pricking the finger several times a day. In this study, we compared different state-of-the-art lancing devices from leading manufacturers regarding lancing pain, and we intended to identify lancing devices that are less painful.

Methods:

First, 165 subjects compared 6 different BG monitoring systems—consisting of a lancing device and a BG meter—at home for 36 days and at least 3 BG tests per day. Second, the subjects directly compared 6 different lancing devices—independent from a BG meter—in a laboratory setting. The test results were collected in questionnaires, and lancing pain was rated on a numerical rating scale.

Results:

One hundred fifty-seven subjects were included in the analysis. Accu-Chek BG monitoring systems were significantly ( p ≤ .006) preferred to competitor BG monitoring systems and were rated by >50% of the subjects as “less painful” than competitor BG monitoring systems. Accu-Chek lancing devices were significantly ( p < .001) preferred to competitor lancing devices and were rated by >60% of the subjects as “less painful” than competitor lancing devices.

Conclusions:

We found significant differences in lancing pain between lancing devices. Diabetes patients clearly preferred lancing devices that cause less lancing pain. In order to improve patient compliance with respect to an adequate glycemic control, the medical staff should preferentially prescribe lancing devices that cause less lancing pain.
An Analysis of the SEVEN® System: Have We Reached the Summit of Needle-Type Sensor Accuracy?
Authors: Wentholt Iris M. E. , DeVries J. Hans
Published: January 2014

In this issue of Journal of Diabetes Science and Technology, Zisser and colleagues show improved sensor accuracy with the newest generation of needle-type sensors as compared to first generation sensors. Can we expect further improvement? It is unknown what the future holds, but there certainly seems much to be gained from improved calibration procedures. In addition, sensor operating times are increasing and it is hoped that this will translate into improved sensor use and thereby into improved glycemic control.
Inspiratory Efforts Achieved in Use of the Technosphere® Insulin Inhalation System
Authors: Smutney Chad C. , Friedman Emil M. , Polidoro John M. , Amin Nikhil
Published: January 2014

Objective:

The Technosphere® Insulin (IT) inhalation system comprises TI powder premetered into unit dose cartridges and the patient-friendly, reusable, breath-powered MedTone® inhaler. This high-resistance system uses a patient's inspiratory effort to effect TI powder de-agglomeration and promote subsequent deep-lung delivery. This study reports on flow and pressure data achieved by patients with diabetes using the MedTone system.

Method:

MedTone inhalers containing empty cartridges were adapted with pneumotach measuring devices to capture inhalation profiles. The measuring apparatuses had negligible impact on the nominal MedTone system resistance level of 0.117 kPa0.5/liters/min. Each of 56 subjects inhaled twice to mimic TI clinical study dosing instructions. Achieved inhalation profiles were characterized by peak inspiratory flow (PIF), peak inspiratory pressure (PIP), and average pressure drop from the time of PIP to 4 s ( Pavg)

Results:

The achieved mean PIF (± standard deviation [SD]) in all subjects was 26.74 (±6.06) liters/min after the first inhalation and was similar to the mean PIF of 26.25 (±6.23) liters/min achieved after the second inhalation. Mean PIP (±SD) achieved by subjects was 8.49 (±2.86) and 8.1 (±2.99) kPa, and mean Pavg drop (±SD) in all subjects was 6.53 (±2.24) and 6.09 (±2.08) kPa after the respective inhalations.

Conclusion:

Patients with diabetes demonstrated consistent inhalation efforts over two inhalations using the MedTone system. The achieved PIFs and PIPs demonstrate the capacity of this population to obtain sufficient inspiratory effort necessary for delivery of TI using the MedTone inhaler. Adequate postpeak pressures were also revealed, further supporting reliable and sustained inhalation efforts.
Display of Glucose Distributions by Date, Time of Day, and Day of Week: New and Improved Methods
Authors: Rodbard David
Published: January 2014

Objective:

There is a need for improved methods for display of glucose distributions to facilitate comparisons by date, time of day, day of the week, and other variables for data obtained using self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM).

Method:

Stacked bar charts are utilized for multiple ranges of glucose values, e.g., very low, low, borderline low, target range, borderline high, high, and very high. Glucose ranges for these categories can be defined by the user, e.g., <40, 40–70, 71–80, 81–140, 141–180, 181–250, and 251–400 mg/dl. Glucose distributions can be displayed by time of day, in relation to meals, by date, or by day of week. The graphic display can be generated using general purpose spreadsheet software such as Microsoft Excel or with special purpose software.

Result:

Stacked bar charts are extremely compact and effective. They facilitate comparison of multiple days, multiple time segments within a day, preprandial and postprandial glucose levels, days of the week, treatment periods, patients, and groups of patients. They are superior to use of pie charts in terms of compactness and in their ability to facilitate comparisons using multiple criteria and multiple subsets of the data. One can identify episodes of hypoglycemia and hyperglycemia and can display standard errors of estimates of percentages. Interpretation of these graphs is readily learned and requires minimal training.

Conclusion:

Use of stacked bar charts is generally superior to use of pie charts for display of glucose distributions and can potentially facilitate the analysis and interpretation of SMBG and CGM data.
An Analysis of Patient Acceptance and Safety of a Prefilled Insulin Injection Device
Authors: Kroon Lisa
Published: January 2014

This article summarizes and interprets the findings of Carter and colleagues in this issue of Journal of Diabetes Science and Technology, a study of the real world use of a prefilled insulin pen device. In this observational study, people with type 1 and type 2 diabetes rated their experience with the SoloSTAR pen device after 6–10 weeks of use. Data on patient satisfaction, product technical complaints, and adverse effects were reported. Randomized, controlled trials are needed that compare the various pen devices and the vial/syringe in terms of accuracy of dosing, adherence to therapy, and ease of use (including patient perception of injection force required) to assess whether a particular method of insulin delivery or pen delivery device provides a clinical advantage over another.
Hypoglycemia Detection in Critical Care Using Continuous Glucose Monitors: An in Silico Proof of Concept Analysis
Authors: Pretty Christopher G. , Chase J. Geoffrey , Compte Aaron Le , Shaw Geoffrey M. , Signal Matthew
Published: January 2014

Background:

Tight glycemic control (TGC) in critical care has shown distinct benefits but has also been proven difficult to obtain. The risk of severe hypoglycemia (<40 mg/dl) has been increased significantly in several, but not all, studies, raising significant concerns for safety. Continuous glucose monitors (CGMs) offer frequent measurement and thus the possibility of using them for early detection alarms to prevent hypoglycemia.

Methods:

This study used retrospective clinical data from the Specialized Relative Insulin Nutrition Titration TGC study covering seven patients who experienced severe hypoglycemic events. Clinically validated metabolic system models were used to recreate a continuous blood glucose profile. In silico analysis was enabled by using a conservative single Gaussian noise model based on reported CGM clinical data from a critical care study [mean absolute percent error (MAPE) 17.4%]. A novel median filter was implemented and further smoothed with a least mean squares-fitted polynomial to reduce sensor noise. Two alarm approaches were compared. An integral-based method is presented that examined the area between a preset threshold and filtered simulated CGM data. An alarm was raised when this value became too low. A simple glycemic threshold method was also used for comparison. To account for random noise skewing the results, each patient record was Monte Carlo simulated 100 times with a different random noise profile for a total of 700 runs. Different alarm thresholds were analyzed parametrically. Results are reported in terms of detection time before the clinically measured event and any false alarms. These retrospective clinical data were used with approval from the New Zealand South Island Regional Ethics Committee.

Results:

The median filter reduced MAPE from 17.4% [standard deviation (SD) 13%] to 9.3% (SD 7%) over the cohort. For the integral-based alarm, median per-patient detection times ranged, t, from −35 minutes (before event) to −170 minutes, with zero to two false alarms per patient over the cohort and different alarm parameters. For a simple glycemic threshold alarm (three consecutive values below threshold), median per-patient alarm times were −10 to −75 minutes and false alarms were zero to seven; however, in one case, five of seven subjects never alarmed at all, despite the hypoglycemic event.

Conclusions:

A retrospective study used clinical hypoglycemic events from a TGC study to develop and analyze an integral-based hypoglycemia alarm for use in critical care TGC studies. The integral-based approach was accurate, provided significant lead time before a hypoglycemic event, alarmed at higher glycemic levels, was robust to sensor noise, and had minimal false alarms. The approach is readily generalizable to similar scenarios, and results would justify a pilot clinical trial to verify this study.
Individuals Achieve More Accurate Results with Meters That Are Codeless and Employ Dynamic Electrochemistry
Authors: Rao Anoop , Wiley Meg , Iyengar Sridhar , Nadeau Dan , Carnevale Julie
Published: January 2014

Background:

Studies have shown that controlling blood glucose can reduce the onset and progression of the long-term microvascular and neuropathic complications associated with the chronic course of diabetes mellitus. Improved glycemic control can be achieved by frequent testing combined with changes in medication, exercise, and diet. Technological advancements have enabled improvements in analytical accuracy of meters, and this paper explores two such parameters to which that accuracy can be attributed.

Methods:

Four blood glucose monitoring systems (with or without dynamic electrochemistry algorithms, codeless or requiring coding prior to testing) were evaluated and compared with respect to their accuracy.

Results:

Altogether, 108 blood glucose values were obtained for each system from 54 study participants and compared with the reference values. The analysis depicted in the International Organization for Standardization table format indicates that the devices with dynamic electrochemistry and the codeless feature had the highest proportion of acceptable results overall (System A, 101/103). Results were significant when compared at the 10% bias level with meters that were codeless and utilized static electrochemistry ( p = .017) or systems that had static electrochemistry but needed coding ( p = .008).

Conclusions:

Analytical performance of these blood glucose meters differed significantly depending on their technologic features. Meters that utilized dynamic electrochemistry and did not require coding were more accurate than meters that used static electrochemistry or required coding.
Stomach Dysfunction in Diabetes Mellitus: Emerging Technology and Pharmacology
Authors: Szarka Lawrence A. , Camilleri Michael
Published: January 2014

Gastroparesis and other types of gastric dysfunction result in substantial morbidity in diabetes patients. The pathophysiology of these disorders is incompletely understood. This article reviews techniques applicable to the assessment of gastric function in diabetes patients, including the measurement of emptying, accommodation, and contractility. Available treatment options are also reviewed, including novel yet unapproved serotonin 5-HT4 agonist pharmacological treatments, as well as the role of endoscopic, surgical, and device treatments of gastroparesis.
Noninvasive Glucose Monitoring: Increasing Accuracy by Combination of Multi-Technology and Multi-Sensors
Authors: Harman-Boehm Ilana , Gal Avner , Raykhman Alexander M. , Naidis Eugene , Mayzel Yulia
Published: January 2014

Background:

The main concern in noninvasive (NI) glucose monitoring methods is to achieve high accuracy results despite the fact that no direct blood or interstitial fluid glucose measurement is performed. An alternative approach to increase the accuracy of NI glucose measurement was previously suggested through a combination of three NI methods: Ultrasonic, electromagnetic, and thermal. This paper provides further explanation about the nature of the implemented technologies, and multi-sensors are presented, as well as a detailed elaboration on the novel algorithm for data analysis.

Methods:

Clinical trials were performed on two different days. During the first day, calibration and six subsequent measurements were performed. During the second day, a “full day” session of about 10 hours took place. During the trial, type 1 and 2 diabetes patients were calibrated and evaluated with GlucoTrack® glucose monitor against HemoCue® (Glucose 201+).

Results:

A total of 91 subjects were tested during the trial period. Clarke error grid (CEG) analysis shows 96% of the readings (on both days 1 and 2) fall in the clinically accepted A and B zones, of which 60% are within zone A. The absolute relative differences (ARDs) yield mean and median values of 22.4% and 15.9%, respectively. The CEG for day 2 of the trial shows 96% of the points in zones A and B, with 57% of the values in zone A. Mean and median ARD values for the readings on day 2 are 23.4% and 16.5%, respectively. The intervals between day 1 (calibration and measurements) and day 2 (measurements only) were 1–22 days, with a median of 6 days.

Conclusions:

The presented methodology shows that increased accuracy was indeed achieved by combining multi-technology and multi-sensors. The approach of integration contributes to increasing the signal-to-noise ratio (glucose to other contributors). A combination of several technologies allows compensation of a possible aberration in one modality by the others, while multi-sensor implementation enables corrections for interference contributions. Furthermore, clinical trials indicate the ability of using the device for a wide range of demography, showing clearly that the calibration is valid for long term.
Comparison Pharmacokinetics of Two Concentrations (0.7% and 1.0%) of Nasulin™, an Ultra-Rapid-Acting Intranasal Insulin Formulation
Authors: Stote Robert , Marbury Thomas , Shi Leon , Miller Michael , Strange Poul
Published: January 2014

Background:

This pharmacokinetic (PK) study was designed to characterize the dose response of two concentrations (0.7% and 1%) of a nasal spray of recombinant regular human insulin in combination with cyclopentadecalactone (CPE-215), a compound that enhances absorption of molecules across mucous membranes (Nasulin™, CPEX Pharmaceuticals). Nasulin has been effective in lowering blood glucose in both normal subjects and diabetes patients, and additional dosing options would allow greater titration flexibility.

Method:

A five-period crossover study of 24 healthy, nonsmoking subjects (ages 18–50, basal metabolic index <33 kg/m2, weight >70 kg) were studied. Subjects were in a fasted state for 5 h before and 45 min after administration for PK assessment and were then given a meal. Each spray contained 100 μl. Doses tested were 25, 35, 50, 70, and 100 U. Maximum concentration (Cmax) and area under the curve (AUC) were estimated for each dose group. Glucose measurements were also performed.

Results:

A dose response (slope of the natural log response versus dose) was demonstrated by baseline-adjusted Cmax of 22, 27, 56, 62, and 84 μU/ml for the 25, 35, 50, 70, and 100 U doses ( p < .0001), respectively, and by baseline-adjusted AUC(0–45 min) values of 491, 592, 1231, 1310, and 1894 μU/ml/min ( p < .0001). Glucose AUC(0–45 min) determinations also demonstrated a pharmacodynamic (PD) dose response.

Conclusions:

Proportional and linear dose responses for both PK and PD parameters were demonstrated for the two concentrations, making multiple doses available for clinical development.
An Analysis of the Mixing Efficiency of Neutral Protamine Hagedorn Cartridges
Authors: Monte Scott V. , Comerford Patrick , Dearing Natalie
Published: January 2014

In this issue of Journal of Diabetes Science and Technology, Kaiser and colleagues conducted an investigation to identify variations in the delivered dose of several different isophane insulin (neutral protamine Hagedorn, NPH) brands that use glass and metal bodies (“bullets”) to facilitate mixing. Using a strategy where multiple pens from each of five different NPH insulin products (Insuman Basal, sanofi-aventis, three metal bullets; Humulin N, Lilly, one glass bullet; Berlinsulin H Basal, Berlin-Chemie, one glass bullet; Insulin B. Braun Basal, two glass bullets; and Protaphane Penfill, NovoNordisk, one glass bullet) were compared at multiple sampling points and over a range of mixing procedures (3, 6, 10, and 20 times), the authors identified deviations in the delivered dose of insulin at initial use and with repeated dosing. At the initial dose, adhering with manufacturer recommendations to conduct the mixing procedure 10–20 times was found to demonstrate minimal deviation and there was no pronounced difference among the products. Decreasing the number of mixing procedures from 10–20 to 3–6 times, a more profound deviation was noted, with the Insuman Basal product demonstrating less variability in comparison to all other products evaluated. A repeated dose study (1, 2, 6, and 10) with only six mixing procedures revealed that the insulin concentration of each dose increased for all products except Insuman Basal. Clinically, numerous factors may contribute to variability observed with subcutaneous administration of isophane insulin. While data presented by Kaiser and colleagues demonstrated that the issue of proper mixing is not trivial, the modest differences observed between and within products both at the initial dose and with repeated dosing may indicate that the clinical relevance of these findings is most applicable to those requiring large doses or, alternatively, those who have otherwise unexplained hypoglycemic episodes.