bluuebunny/crossref_metadata_2025 huggingface dataset:
Data Processing for Noninvasive Continuous Glucose Monitoring with a Multisensor Device
Authors: Mueller Martin , Talary Mark S. , Falco Lisa , De Feo Oscar , Stahel Werner A. , Caduff Andreas
Published: January 2014

Background:

Impedance spectroscopy has been shown to be a candidate for noninvasive continuous glucose monitoring in humans. However, in addition to glucose, other factors also have effects on impedance characteristics of the skin and underlying tissue.

Method:

Impedance spectra were summarized through a principal component analysis and relevant variables were identified with Akaike's information criterion. In order to model blood glucose, a linear least-squares model was used. A Monte Carlo simulation was applied to examine the effects of personalizing models.

Results:

The principal component analysis was able to identify two major effects in the impedance spectra: A blood glucose-related process and an equilibration process related to moisturization of the skin and underlying tissue. With a global linear least-squares model, a coefficient of determination ( R2) of 0.60 was achieved, whereas the personalized model reached an R2 of 0.71. The Monte Carlo simulation proved a significant advantage of personalized models over global models.

Conclusion:

A principal component analysis is useful for extracting glucose-related effects in the impedance spectra of human skin. A linear global model based on Solianis Multisensor data yields a good predictive power for blood glucose estimation. However, a personalized linear model still has greater predictive power.
Glycated Albumin Modulates Endothelial Cell Thrombogenic and Inflammatory Responses
Authors: Rubenstein David A. , Maria Zahra , Yin Wei
Published: January 2014

Background:

It has become established that a diabetic vasculature promotes cardiovascular disease progression via changes to endothelial cells, platelets, and the interactions of these cells. It is believed that the majority of these changes are induced by the presence of advanced glycation end products (AGEs), which permanently alter various functions. Studies have shown that platelets perpetuate endothelial cell responses under these conditions. However, the role of changes in endothelial cell thrombogenicity and inflammatory responses, after subjected to AGEs, has not been characterized. Our objective was to evaluate the effects of AGEs on these functions.

Methods:

To accomplish this, albumin was chemically modified by exposure to glucose for up to 8 weeks, and endothelial cells were subjected to glycated albumin for up to 5 days in a cell culture system. A time course for changes in endothelial cell viability, density, morphology, and metabolic activity were investigated, along with the surface expression of intercellular adhesion molecule-1, thrombomodulin, tissue factor, connexin-43, and caveolin-1.

Results:

Endothelial cells exposed to irreversibly glycated albumin were less viable, proliferated slower, and had a lower metabolic activity as compared to cells exposed to nonglycated albumin. Endothelial cells that were exposed to any glycated albumin were procoagulant and proinflammatory as compared with all other conditions. There were no overall trends in the expression of connexin-43 or caveolin-1.

Conclusions:

Our data suggest that the presence of irreversible glycated albumin is deleterious to endothelial cells, makes endothelial cells more procoagulant, and promotes inflammatory responses. It is therefore possible that endothelial cell activation may precede and promote platelet activation during diabetic conditions.
Effect of Diabetes Mellitus on Outcomes of Hyperglycemia in a Mixed Medical Surgical Intensive Care Unit
Authors: Schlussel Andrew T. , Holt Danielle B. , Crawley Eric A. , Lustik Michael B. , Wade Charles E. , Uyehara Catherine F. T.
Published: January 2014

Background:

Intensive insulin therapy and degree of glycemic control in critically ill patients remains controversial, particularly in patients with diabetes mellitus. We hypothesized that diabetic patients who achieved tight glucose control with continuous insulin therapy would have less morbidity and lower mortality than diabetic patients with uncontrolled blood glucose.

Method:

A retrospective chart review was performed on 395 intensive care unit (ICU) patients that included 235 diabetic patients. All patients received an intravenous insulin protocol targeted to a blood glucose (BG) level of 80–140mg/dl. Outcomes were compared between (a) nondiabetic and diabetic patients, (b) diabetic patients with controlled BG levels (80–140mg/dl) versus uncontrolled levels (>140 mg/dl), and (c) diabetic survivors and nonsurvivors.

Results:

Diabetic patients had a shorter ICU stay compared to nondiabetic patients (10 ± 0.7 vs 13 ± 1.1, p = .01). The mean BG of the diabetic patients was 25% higher on average in the uncontrolled group than in the controlled (166 ± 26 vs 130 ± 9.4 mg/dl, p < .01). There was no difference in ICU and hospital length of stay (LOS) between diabetic patients who were well controlled compared to those who were uncontrolled. Diabetic nonsurvivors had a significantly higher incidence of hypoglycemia (BG <60 mg/dl) compared to diabetic survivors.

Conclusions:

The results showed that a diagnosis of diabetes was not an independent predictor of mortality, and that diabetic patients who were uncontrolled did not have worse outcomes. Diabetic nonsurvivors were associated with a greater amount of hypoglycemic episodes, suggesting these patients may benefit from a more lenient blood glucose protocol.
DIAMAP: A Road Map for Diabetes Research in Europe
Authors: Hills Sarah , Halban Philippe A.
Published: January 2014

The DIAMAP Project, which has drawn up a road map for diabetes research in Europe, has now concluded, and the results are available in the form of a report and searchable databases. The DIAMAP road maps provide strategic guidance for diabetes research activity and investment in Europe, with the person with diabetes and a broad approach to research being integral to the process.
Analysis of the Environmental Impact of Insulin Infusion Sets Based on Loss of Resources with Waste
Authors: Pfützner Andreas , Musholt Petra B. , Malmgren-Hansen Bjoern , Nilsson Nils H. , Forst Thomas
Published: January 2014

Insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] requires regular change of infusion sets every 2–3 days in order to minimize the risk of skin irritations or other adverse events. This has been discussed to be a potential burden to the environment. The purpose of this analysis was to perform an environmental assessment of insulin pump infusion sets based on loss of resources occurring during incineration of the discarded products and by means of a lifecycle concept used to weight a material in relation to its rareness on earth and its consumption. In addition to five infusion sets (Inset30, InsetII, Comfort, Quick-set, and Cleo), a patch pump (Omnipod) was also included in this analysis. The annual loss in waste of the so called “person reserve” of 3 days of catheter use was compared with daily consumption of a cup of coffee in a disposable paper cup and to a soft drink in an aluminum can. The weight-based loss in resources through waste for the infusion sets (except for Cleo) corresponded to 70–200% of the loss of resources for a coffee cup (Cleo, 320%; Omnipod, 1,821,600%) and to 1–3% of the loss from an aluminum soft drink can (Cleo, 5%; Omnipod, 31,200%). The loss or resources by use of infusion sets used in insulin pump therapy appears to be low and is similar to the burden induced by the uptake of one cup of coffee per day. The loss or resources with regular CSII is considerably lower than the loss or resources induced by patch pumps.
Nanotechnology in Elevation of the Worldwide Impact of Obesity and Obesity-Related Diseases: Potential Roles in Human Health and Disease
Authors: Eldaw Abdellatif
Published: January 2014

Current worldwide data show epidemics of obesity and type 2 diabetes with no real solutions apart from continuous calls to changing lifestyle and food habits. Despite health messages that are communicated by health authorities, the epidemic is growing. More people are affected with health consequences that are usually frightening as more resources are wasted, especially in areas where health care and resources are lacking.

Nanotechnology applications in food industry present practical approaches that help produce more tasty food with little calories, functional foods, and nutritional supplements and alter the fats and sugar contents of our foods with potential for many more applications. Consequently, this opens more windows to better control of many nutritional deficiencies as well as obesity and type 2 diabetes, especially among children and young adults who are addicted to fast food. With such potential, food producers, policy makers, health authorities, food scientists, and governments need to collaborate and make all possible efforts to fund and support research in different areas of food produced using nanotechnology.

So far, consumers are not prepared to accept food produced using nanotechnology, mainly because information on the safety of such products are not enough. This issue needs to be addressed and researched well using suitable risk assessment methodologies. Consumers need to be assured, and involved as well, to avoid the “refusal state” that still exists against many safe products such as genetically modified organisms and irradiated food. There is the possibility that consumers could perceive that they will bear the potential risks posed by nanotechnology applications while the benefits will accrue mainly to others, such as food processors or farmers.
Accuracy of the CONTOUR® Blood Glucose Monitoring System
Authors: Harrison Bern , Leazenby Cheryl , Halldorsdottir Solveig
Published: January 2014

Objective:

The aim of the study was to assess the accuracy of the CONTOUR® blood glucose monitoring system (BGMS) according to the International Organization for Standardization's International Standard 15197 (ISO 15197:2003) guidelines and to more stringent criteria.

Method:

Finger stick blood samples from 105 subjects with diabetes (25 with type 1, 77 with type 2, and 3 with type unknown) were tested using the CONTOUR BGMS and YSI glucose analyzer.

Results:

99.3% of results were within ISO 15197:2003 criteria (±15 mg/dl of YSI results at glucose concentrations <75 mg/dl and ±20% at glucose concentrations ≥75 mg/dl). Additionally, 96.7% of results were accurate according to more stringent criteria (±15 mg/dl of YSI results for glucose concentrations <100 mg/dl and ±15% for glucose concentrations ≥100 mg/dl). Error grid analysis showed that 99.3% and 0.7% of results were within zones A and B, respectively.

Conclusion:

The CONTOUR BGMS exceeded both the minimum acceptable accuracy based on ISO 15197:2003 and the more stringent accuracy criteria.
Design and Fabrication of a High-Performance Electrochemical Glucose Sensor
Authors: Vaddiraju Santhisagar , Legassey Allen , Wang Yan , Qiang Liangliang , Burgess Diane J. , Jain Faquir , Papadimitrakopoulos Fotios
Published: January 2014

Objective:

Development of electrochemical sensors for continuous glucose monitoring is currently hindered by a variety of problems associated with low selectivity, low sensitivity, narrow linearities, delayed response times, hysteresis, biofouling, and tissue inflammation. We present an optimized sensor architecture based on layer stratification, which provides solutions that help address the aforementioned issues.

Method:

The working electrode of the electrochemical glucose sensors is sequentially coated with five layers containing: (1) electropolymerized polyphenol (PPh), (2) glutaraldehyde-immobilized glucose oxidase (GOx) enzyme, (3) dip-coated polyurethane (PU), (4) glutaraldehyde-immobilized catalase enzyme, and (5) a physically cross linked polyvinyl alcohol (PVA) hydrogel membrane. The response of these sensors to glucose and electroactive interference agents (i.e., acetaminophen) was investigated following application of the various layers. Sensor hysteresis (i.e., the difference in current for a particular glucose concentration during ascending and descending cycles after 200 s) was also investigated.

Results:

The inner PPh membrane improved sensor selectivity via elimination of electrochemical interferences, while the third PU layer afforded high linearity by decreasing the glucose-to-O2 ratio. The fourth catalase layer improved sensor response time and eliminated hysteresis through active withdrawal of GOx-generated H2O2 from the inner sensory compartments. The outer PVA hydrogel provided mechanical support and a continuous pathway for diffusion of various participating species while acting as a host matrix for drug-eluting microspheres.

Conclusions:

Optimal sensor performance has been achieved through a five-layer stratification, where each coating layer works complementarily with the others. The versatility of the sensor design together with the ease of fabrication renders it a powerful tool for continuous glucose monitoring.
Average Daily Risk Range as a Measure of Glycemic Risk is Associated with Mortality in the Intensive Care Unit: A Retrospective Study in a Burn Intensive Care Unit
Authors: Farhy Leon S. , Ortiz Edward A. , Kovatchev Boris P. , Mora Alejandra G. , Wolf Steven E. , Wade Charles E.
Published: January 2014

Background:

Although tight glycemic control has been associated with improved outcomes in the intensive care unit (ICU), glycemic variability may be the influential factor in mortality. The main goal of the study was to relate blood glucose (BG) variability of burn ICU patients to outcomes using a sensitive measure of glycemic variability, the average daily risk range (ADRR).

Method:

Data from patients admitted to a burn ICU were used. Patients were matched by total body surface area (TBSA) and injury severity score (ISS) to test whether increased BG variability measured by ADRR was associated with higher mortality risk and whether we could identify ADRR-based classifications associated with the degree of risk.

Results:

Four ADRR classifications were identified: Low risk, medium-low, medium-high, and high. Mortality progressively increased from 25% in the low-risk group to over 60% in the high-risk group ( p < .001). In a post hoc analysis, age also contributed to outcome. Younger (age < 43 years) survivors and nonsurvivors matched by TBSA and ISS had no significant difference in age, mean BG or standard deviation of BG; however, nonsurvivors had higher ADRR ( p < .01).

Conclusions:

Independent of injury severity, glycemic variability measured by the ADRR was significantly associated with mortality in the ICU. When age was considered, ADRR was the only measure of glycemia significantly associated with mortality in younger patients with burns.
Dynamic Electrochemistry: A Step in the Right Direction
Authors: Rice Mark J.
Published: January 2014

Variation in hematocrit is a serious but underappreciated interference to accurate point-of-care glucose measurement. Using a meter employing new technology of dynamic electrochemistry, Musholt and colleagues present in vitro data in this issue of Journal of Diabetes Science and Technology demonstrating improved glucose accuracy over a wide range of hematocrits. Although this may have some importance for patients testing in the home environment, the essential application of this new technology will be in the critical care and perioperative environment, where wide swings in hematocrit are common. Because these meters are in use with great frequency in the hospital where accurate glucose measurement is vital, mitigating this interference is a welcome addition to our diagnostic armamentarium.
Dose Accuracy of the ClikSTAR, NovoPen 4, and Luxura Insulin Pens: Results of Laboratory and Field Studies
Authors: Friedrichs Arnd , Basso Nils , Adler Steffen
Published: January 2014

Background:

A high dosing accuracy is needed to maintain normal glycemia in patients with diabetes. This study investigated the dose accuracy of the commonly used reusable insulin pens ClikSTAR®, NovoPen® 4, and Luxura®.

Methods:

Pens were tested in a laboratory setting by one trained technician who delivered four doses of 30 U from each of 15 pens per pen model (a total of 60 doses from each pen model). Pens were also tested in a simulated clinical setting by 48 people with diabetes. Each participant delivered 27 doses: Three doses of 30 U from each of three pens per pen model. Overall, the technician delivered 180 doses and the participants 1296 doses.

Results:

All pens met the tolerance limits defined by the German edition of the International Standardization Organization (ISO) 11608-1: 2000 standard [30 ± 1.5 U (28.5–31.5 U)]. All doses were delivered within the limits proposed by the ISO, except for two doses with Luxura in the clinical setting. In laboratory testing, the mean dose delivered by ClikSTAR (29.69 U) or Luxura (29.89 U) was less than the expected 30 U and significantly less than the mean dose delivered by NovoPen 4 (30.04 U; p < .001 for both comparisons). Similar results were observed in the simulated clinical setting. NovoPen 4 had the greatest variance in laboratory testing but the least in the simulated clinical setting.

Conclusions:

This study demonstrates comparable dose accuracy and variability of the ClikSTAR, Luxura, and NovoPen 4 insulin pens. The slight differences in mean doses between pens are unlikely to be clinically significant.
FlexTouch: A Prefilled Insulin Pen with a Novel Injection Mechanism with Consistent High Accuracy at Low- (1 U), Medium- (40 U), and High- (80 U) Dose Settings
Authors: Wielandt Jakob Oest , Niemeyer Marcus , Hansen Marianne Rye , Bucher Ditlef , Thomsen Niels Bjerrum
Published: January 2014

Background:

FlexTouch® is the only prefilled insulin pen that utilizes an easy touch button that does not extend at any dose in place of a push-button extension. Rigorous testing has shown that the new FlexTouch pen accurately and consistently delivers insulin doses.

Methods:

This study assessed dose accuracy of FlexTouch, KwikPen®, and SoloSTAR®. Dose accuracy for minimum, medium, and maximum doses of each pen type (1, 40, and 80 U for FlexTouch and SoloSTAR and 1, 30, and 60 U for KwikPen) was assessed.

Results:

FlexTouch delivered all doses consistently, as demonstrated by low standard deviations. FlexTouch showed similar accuracy to KwikPen at 1 U and to SoloSTAR at 40 and 80 U. However, FlexTouch was significantly more accurate at delivering 1 U of insulin than SoloSTAR ( p < .0001).

Conclusions:

This study demonstrates that FlexTouch, a new prefilled pen, delivers insulin accurately and consistently at low, medium, and high doses. In addition, FlexTouch is currently the only prefilled pen that has a push button that does not extend at any dose, making FlexTouch easier to use than other pens.
Analysis: Desirable Attributes of Insulin Injection Pens That Drive Patient Preference and Compliance
Authors: Zahn Jeffrey D.
Published: January 2014

Insulin pens are used by approximately half of worldwide insulin users. Insulin pens have made insulin injections easier compared to traditional vial and syringe injections. In an article in this issue of Journal of Diabetes Science and Technology, Dr. Asakura discusses several important design parameters, which are considered during refillable insulin-injection pen design. Ease of cartridge replacement, insulin-dose setting dial use, injection, and prominence of audible clicks can all affect overall dose accuracy and user friendliness of insulin pens in patients suffering from diabetes and related comorbidities. These parameters, along with patient introduction from prescribing physicians and level of training provided, drives patient pen selection and injection-regimen compliance to control their blood sugar.
A Randomized, Open-Label, Comparative Crossover Handling Trial between Two Durable Pens in Patients with Type 1 or 2 Diabetes Mellitus
Authors: Sommavilla Bärbel , Pietranera Giacomo
Published: January 2014

Background:

This open-label, randomized, comparative crossover usability study investigated preference between durable insulin pens, NovoPen® 4 and NovoPen 3, among patients with types 1 and 2 diabetes.

Methods:

In a timed test, 82 current NovoPen 3 users (mean age, 48.5 years) assessed intuitiveness of NovoPen 4. After timed training, this group and 34 insulin-naïve patients (mean age, 61.8 years) were randomized to a handling evaluation of NovoPen 4 followed by NovoPen 3, or vice versa, in which participants made three injections into a foam cushion. A device-specific questionnaire was filled out for each pen. A third questionnaire asked participants to compare pens.

Results:

Current NovoPen 3 users completed the intuitive assessment of NovoPen 4 in an average time of 1.94 min (range, 0.57–4.98 min). The training of insulin-naïve patients occurred in slightly less time with NovoPen 4 than with NovoPen 3 but did not reach significance (9.9 versus 11.5 min; p = .32). Survey responses showed that both groups had less difficulty and were more confident in handling NovoPen 4 than NovoPen 3; 96.3% of the NovoPen 3 users and 100% of the insulin-naïve group preferred to use NovoPen 4 ( p < .0001).

Conclusion:

Patients currently using NovoPen 3 or who were insulin naïve expressed a preference for NovoPen 4 in this study, reporting it to be simpler to learn and easier to use than NovoPen 3. NovoPen 4 may help facilitate insulin therapy among newly diagnosed patients and potentially improve adherence and treatment satisfaction among current NovoPen 3 users.
A Pan-European and Canadian Prospective Survey to Evaluate Patient Satisfaction with the SoloSTAR Insulin Injection Device in Type 1 and Type 2 Diabetes
Authors: Hancu Nicolae , Czupryniak Leszek , Genestin Elisabeth , Sourij Harald
Published: January 2014

Objective:

This study evaluated patient satisfaction with SoloSTAR® (sanofi-aventis), a prefilled insulin pen device for injection of insulin glargine or insulin glulisine.

Methods:

This was a 6–8-week multicenter ( n = 652), observational, prospective Pan-European and Canadian registry study in patients with diabetes mellitus ( n = 6542) who recently switched to or started treatment with insulin glargine and/or insulin glulisine using SoloSTAR or were insulin naïve. At the baseline visit, patients were asked to evaluate their satisfaction with their previous device, if applicable. After 6–8 weeks of SoloSTAR use, patients were asked to rate their satisfaction.

Results:

Overall, 6481 patients (mean age 54 years, 48.7% male, 72% type 2 diabetes) were analyzed in this study. Of these, 4995 (77.1%) patients had used insulin before the study and 1641 (32.9%) and 3395 (68.0%) patients had previously used prefilled and/or reusable pens, respectively. During the study, SoloSTAR was used to administer insulin glargine and/or insulin glulisine by 97.3% and 36.0% of patients, respectively (both: 27.0%). Most patients rated SoloSTAR as “excellent/good” for ease of use (97.9%), learning to use (98.3%), selecting the dose (97.6%), and reading the dose (95.1%). Most patients rated ease of use (88.4%) and injecting a dose (84.5%) with SoloSTAR as “much easier/easier” versus their previous pen. Overall, 98% planned to continue using SoloSTAR. No safety concerns were reported.

Conclusion:

This European and Canadian survey shows that SoloSTAR was well accepted in this large patient population. Most patients preferred SoloSTAR to their previous pen and planned to continue SoloSTAR use.
Impact of Epidemic Rates of Diabetes on the Chinese Blood Glucose Testing Market
Authors: Hu Jamie , Zhang Xian-En
Published: January 2014

China has become the country with the largest diabetes mellitus population in the world since the 1990s. About 100 million diabetes cases have been diagnosed since 2008. Handheld blood glucose meters and test strips are urgently needed for daily patient measurement. The glucose monitor with a screen-printed carbon-based glucose electrode has been in commercial production since 1994. Since then, approximately 20 companies have been involved in manufacturing and marketing meters and test strips in China. The current market and production volume and updates on technology issues are discussed in this article.
Bringing the Artificial Pancreas Home: Telemedicine Aspects
Authors: Lanzola Giordano , Capozzi Davide , Serina Nadia , Magni Lalo , Bellazzi Riccardo
Published: January 2014

The design and implementation of telemedicine systems able to support the Artificial Pancreas need careful choices to cope with technological requirements while preserving performance and decision support capabilities. This article addresses the issue of designing a general architecture for the telemedicine components of an Artificial Pancreas and illustrates a viable solution that is able to deal with different use cases and is amenable to support mobile-health implementations. The goal is to enforce interoperability among the components of the architecture and guarantee maximum flexibility for the ensuing implementations. Thus, the design stresses modularity and separation of concerns along with adoption of clearly defined protocols for interconnecting the necessary components. This accounts for the implementation of integrated telemedicine systems suitable as short-term monitoring devices for supporting validation of closed-loop algorithms as well as devices meant to provide a lifelong tighter control on the patient state once the Artificial Pancreas has become the preferred treatment for patients with diabetes.
An Analysis of the Usability of Inpatient Insulin Ordering in Three Computerized Provider Order Entry Systems
Authors: Neinstein Aaron , Cucina Russ
Published: January 2014

Background:

Insulin is a highly scrutinized drug in hospitals since it is both frequently used and high risk. As the insulin ordering process makes a transition from pen and paper to computerized provider order entry (CPOE) systems, the effective design of these systems becomes critical. There are fundamental usability principles in the field of human-computer interaction design, which help make interfaces that are effective, efficient, and satisfying. To our knowledge, there has not been a study that specifically looks at how these principles have been applied in the design of insulin orders in a CPOE system.

Method:

We analyzed the usability of inpatient insulin ordering in three widely deployed CPOE systems—two commercially marketed systems and the U.S. Department of Veterans Affairs VistA Computerized Patient Record System. We performed a usability analysis using aspects of three different methods. Our first goal was to note each instance where a usability principle was either upheld or not upheld. Our second goal was to discover ways in which CPOE designers could exploit usability principles to make insulin ordering safer and more intuitive in the future.

Results:

Commonly encountered usability principles included constraints, obviousness/self-evidence, natural mapping, feedback, and affordance. The three systems varied in their adherence to these principles, and each system had varying strengths and weaknesses.

Conclusion:

Adherence to usability principles is important when building a CPOE system, yet designers observe them to varying degrees. A well-designed CPOE interface allows a clinician to focus more of his or her mental energy on clinical decisions rather than on deciphering the system itself. In the future, intelligent design of CPOE insulin orders can be used to help optimize and modernize management of hyperglycemia in the hospital.
Analysis of Novel Methods to Determine the Accuracy of the OmniPod Insulin Pump: A Key Component of the Artificial Pancreas System
Authors: Ochoa Manuel , Ziaie Babak
Published: January 2014

In this issue of Journal of Diabetes Science and Technology, Zisser and collegues describe two inexpensive methods for accurate measurement of dosage delivered by OmniPod insulin pump. The first method is based on imaging a meniscus movement in a micro-pipette and using simple image analysis; the second relies on using a digital microscope to measure the volume of a dispensed droplet while it is still attached to the cannula tip. Both methods produce accurate measurements for doses >0.2 U, and the latter method is especially appropriate for doses <0.2 U, with accuracies down to 0.9%.
Diabetic Foot Ulcers and Vascular Insufficiency: Our Population Has Changed, but Our Methods Have Not
Authors: Armstrong David G. , Cohen Kelman , Courric Stephane , Bharara Manish , Marston William
Published: January 2014

Diabetic foot complications are increasing in prevalence worldwide. Care and attention to these complications have improved greatly. Many advanced therapies are now being investigated or taken through final stages of clinical studies worldwide. However, the data upon which assumptions regarding morbidity, healing, and mortality have been based are grossly outdated. The purpose of this brief article is to report on current data regarding neuropathic and neuroischemic wounds and to propose that the latter category of advanced-stage diabetic foot wound may now be emerging as the most commonly encountered lesion in the developed world. Unfortunately, it is still systematically excluded from most clinical study criteria. Additionally, just as in the care of cancer, we call for therapy of these advanced-stage diabetic foot ulcers to be managed in similarly interdisciplinary centers where patients may have access to potentially beneficial clinical trials.
Stress Hyperglycemia in Pediatric Critical Illness: The Intensive Care Unit Adds to the Stress!
Authors: Srinivasan Vijay
Published: January 2014

Stress hyperglycemia (SH) commonly occurs during critical illness in children. The historical view that SH is beneficial has been questioned in light of evidence that demonstrates the association of SH with worse outcomes. In addition to intrinsic changes in glucose metabolism and development of insulin resistance, specific intensive care unit (ICU) practices may influence the development of SH during critical illness. Mechanical ventilation, vasoactive infusions, renal replacement therapies, cardiopulmonary bypass and extracorporeal life support, therapeutic hypothermia, prolonged immobility, nutrition support practices, and the use of medications are all known to mediate development of SH in critical illness. Tight glucose control (TGC) to manage SH has emerged as a promising therapy to improve outcomes in critically ill adults, but results have been inconclusive. Large variations in ICU practices across studies likely resulted in inconsistent results. Future studies of TGC need to take into account the impact of commonly used ICU practices and, ideally, standardize protocols in an attempt to improve the accuracy of conclusions from such studies.
Hypoglycemia in Critically Ill Children
Authors: Faustino E. Vincent S. , Hirshberg Eliotte L. , Bogue Clifford W.
Published: January 2014

Background:

The practice of glycemic control with intravenous insulin in critically ill patients has brought clinical focus on understanding the effects of hypoglycemia, especially in children. Very little is published on the impact of hypoglycemia in this population. We aimed to review the existing literature on hypoglycemia in critically ill neonates and children.

Methods:

We performed a systematic review of the literature up to August 2011 using PubMed, Ovid MEDLINE and ISI Web of Science using the search terms “hypoglycemia or hypoglyc*” and “critical care or intensive care or critical illness”. Articles were limited to “all child (0–18 years old)” and “English”.

Results:

A total of 513 articles were identified and 132 were included for review. Hypoglycemia is a significant concern among pediatric and neonatal intensivists. Its Definition is complicated by the use of a biochemical measure (i.e., blood glucose) for a pathophysiologic problem (i.e., neuroglycopenia). Based on associated outcomes, we suggest defining hypoglycemia as <40–45 mg/dl in neonates and <60–65 mg/dl in children. Below the suggested threshold values, hypoglycemia is associated with worse neurological outcomes, increased intensive care unit stay, and increased mortality. Disruptions in carbohydrate metabolism increase the risk of hypoglycemia in critically ill children. Prevention of hypoglycemia, especially in the setting of intravenous insulin use, will be best accomplished by the combination of accurate measuring techniques, frequent or continuous glucose monitoring, and computerized insulin titration protocols.

Conclusion:

Studies on hypoglycemia in critically ill children have focused on spontaneous hypoglycemia. With the current practice of maintaining blood glucose within a narrow range with intravenous insulin, the risk factors and outcomes associated with insulin-induced hypoglycemia should be rigorously studied to prevent hypoglycemia and potentially improve outcomes of critically ill children.
Population-Based Study of Severe Hypoglycemia Requiring Emergency Medical Service Assistance Reveals Unique Findings
Authors: Parsaik Ajay K. , Carter Rickey E. , Pattan Vishwanath , Myers Lucas A. , Kumar Hamit , Smith Steven A. , Russi Christopher S. , Levine James A. , Basu Ananda , Kudva Yogish C.
Published: January 2014

Objective:

The objective is to report a contemporary population-based estimate of hypoglycemia requiring emergency medical services (EMS), its burden on medical resources, and its associated mortality in patients with or without diabetes mellitus (DM, non-DM), which will enable development of prospective strategies that will capture hypoglycemia promptly and provide an integrated approach for prevention of such episodes.

Methods:

We retrieved all ambulance calls activated for hypoglycemia in Olmsted County, Minnesota, between January 1, 2003 and December 31, 2009.

Results:

A total of 1473 calls were made by 914 people (DM 8%, non-DM 16%, unknown DM status 3%). Mean age was 60 ± 16 years with 49% being female. A higher percentage of calls were made by DM patients (87%) with proportionally fewer calls coming from non-DM patients (11%) (chi-square test, p < .001), and the remaining 2% calls by people with unknown DM status. Emergency room transportation and hospitalization were significantly higher in non-DM patients compared to DM patients ( p < .001) and type 2 diabetes mellitus compared to type 1 diabetes mellitus ( p < .001). Sulphonylureas alone or in combination with insulin varied during the study period ( p = .01). The change in incidence of EMS for hypoglycemia was tracked during this period. However, causality has not been established. Death occurred in 240 people, 1.2 (interquartile range 0.2–2.7) years after their first event. After adjusting for age, mortality was higher in non-DM patients compared with DM patients ( p < .001) but was not different between the two types of DM.

Conclusions:

The population burden of EMS requiring hypoglycemia is high in both DM and non-DM patients, and imposes significant burden on medical resources. It is associated with long-term mortality.
Analysis of Use of an Automated Bolus Calculator Reduces Fear of Hypoglycemia and Improves Confidence in Dosage Accuracy in Type 1 Diabetes Mellitus Patients Treated with Multiple Daily Insulin Injections
Authors: Schwartz Frank L. , Guo Aili , Marling Cynthia R. , Shubrook Jay H.
Published: January 2014

In this issue of Journal of Diabetes Science and Technology, Barnard and colleagues evaluate the use of the ACCU-CHEK® Aviva Expert blood glucose meter/bolus advisor system in patients with type 1 diabetes mellitus. Hypoglycemia is a major limiting factor to intensive glucose control, and fear of hypoglycemia, especially in those who have experienced severe reactions, is a major barrier. The bolus advisor improved overall glucose control and increased adherence by overcoming the patients' fear of hypoglycemia, giving them more confidence to give adequate doses of insulin to control hyperglycemia. In this review, we discuss other human factors that become barriers to intensive control, which can benefit from new technologies, including numeracy literacy, information overload, time required for diabetes self-care, and device incompatibility.
Pilot Study for the Evaluation of Morphological and Functional Changes in Retinal Blood Flow in Patients with Insulin Resistance and/or Type 2 Diabetes Mellitus
Authors: Forst Thomas , Weber Matthias M. , Mitry Michael , Schöndorf Thomas , Forst Senait , Tanis Mukadar , Pfützner Andreas , Michelson Georg
Published: January 2014

Background:

The aim of this study was to investigate early morphological and functional pathology in the retinal micro-circulation in patients with insulin resistance and/or type 2 diabetes mellitus (T2DM).

Methods:

Fifty-four subjects, without features of retinopathy under ophthalmological investigation, were recruited for study participation and were classifed into three study groups according to their metabolic staging: (1) Group C comprised nondiabetic, insulin-sensitive subjects with a BMI <28kg/m2; (2) Group IR comprised nondiabetic, insulin-resistant, obese subjects with a BMI ≥28 kg/m2; and (3) Group DM comprised patients with manifested T2DM. Retinal microvascular blood flow was assessed using scanning laser doppler flowmetry (Heidelberg Retina Flowmeter) before and after flicker light stimulation (10 Hz; Photo Stimulater 750).

Results:

No significant difference was observed in retinal blood flow (RBF) among the three groups, neither at baseline nor after stimulating the retina with flicker light. The arterial wall-to-lumen ratio (WLR) tended to be smaller in Group DM compared with Group C, and was significantly lower when comparing Group IR with Group C. When the subjects were grouped according to their insulin resistance, a steady decline in RBF and WLR could be observed with increasing insulin resistance.

Conclusions:

In conclusion, laser scanner flowmetry of the retina was found to detect very early changes in microvascular blood flow. Development of insulin resistance seems to be an important component in the deterioration of RBF.
Closing the Gap: Eliminating Health Care Disparities among Latinos with Diabetes Using Health Information Technology Tools and Patient Navigators
Authors: López Lenny , Grant Richard W.
Published: January 2014

Latinos have higher rates of diabetes and diabetes-related complications compared to non-Latinos. Clinical diabetes self-management tools that rely on innovative health information technology (HIT) may not be widely used by Latinos, particularly those that have low literacy or numeracy, low income, and/or limited English proficiency. Prior work has shown that tailored diabetes self-management educational interventions are feasible and effective in improving diabetes knowledge and physiological measures among Latinos, especially those interventions that utilize tailored coaching and navigator programs. In this article, we discuss the role of HIT for diabetes management in Latinos and describe a novel “eNavigator” role that we are developing to increase HIT adoption and thereby reduce health care disparities.
Guidelines for Application of Continuous Subcutaneous Insulin Infusion (Insulin Pump) Therapy in the Perioperative Period
Authors: Boyle Mary E. , Seifert Karen M. , Beer Karen A. , Apsey Heidi A. , Nassar Adrienne A. , Littman Stephanie D. , Magallanez Janice M. , Schlinkert Richard T. , Stearns Joshua D. , Hovan Michael J. , Cook Curtiss B.
Published: January 2014

Case reports indicate that diabetes patients receiving outpatient insulin pump therapy have been allowed to continue treatment during surgical procedures. Although allowed during surgery, there is actually little information in the medical literature on how to manage patients receiving insulin pump therapy during a planned surgical procedure. A multidisciplinary work group reviewed current information regarding the use of insulin pumps in the perioperative period. Although the work group identified safety issues specific to surgical scenarios, it believed that with the use of standardized guidelines and a checklist, continuation of insulin pump therapy during the perioperative period is feasible. A sample set of protocols have been developed and are summarized. A policy outlining clear procedures should be established at the institutional level to guide physicians and other staf if the devices are to be employed during the perioperative period. Additional clinical experience with the technology in surgical scenarios is needed, and consensus should be developed for insulin pump use in the perioperative phases of care.
Insulin Fibrillation and Protein Design: Topological Resistance of Single-Chain Analogs to Thermal Degradation with Application to a Pump Reservoir
Authors: Phillips Nelson B. , Whittaker Jonathan , Ismail-Beigi Faramarz , Weiss Michael A.
Published: January 2014

Insulin is susceptible to thermal fibrillation, a misfolding process that leads to nonnative cross-β assembly analogous to pathological amyloid deposition. Pharmaceutical formulations are ordinarily protected from such degradation by sequestration of the susceptible monomer within native protein assemblies. With respect to the safety and efficacy of insulin pumps, however, this strategy imposes an intrinsic trade-off between pharmacokinetic goals (rapid absorption and clearance) and the requisite physical properties of a formulation (prolonged shelf life and stability within the reservoir). Available rapid-acting formulations are suboptimal in both respects; susceptibility to fibrillation is exacerbated even as absorption is delayed relative to the ideal specifications of a closed-loop system. To circumvent this molecular trade-off, we exploited structural models of insulin fibrils and amyloidogenic intermediates to define an alternative protective mechanism. Single-chain insulin (SCI) analogs were shown to be refractory to thermal fibrillation with maintenance of biological activity for more than 3 months under conditions that promote the rapid fibrillation and inactivation of insulin. The essential idea exploits an intrinsic incompatibility between SCI topology and the geometry of cross-β assembly. A peptide tether was thus interposed between the A- and B-chains whose length was (a) sufficiently long to provide the “play” needed for induced fit of the hormone on receptor binding and yet (b) sufficiently short to impose a topological barrier to fibrillation. Our findings suggest that ultrastable monomeric SCI analogs may be formulated without protective self-assembly and so permit simultaneous optimization of pharmacokinetics and reservoir life.
Prediction and Prevention of Treatment-Related Inpatient Hypoglycemia
Authors: Elliott Michael B. , Schafers Stephen J. , McGill Janet B. , Tobin Garry S.
Published: January 2014

Background:

Prolonged severe hypoglycemia (SH) in hospitalized patients is associated with increased morbidity and mortality. This study was undertaken to identify risk factors for SH, to apply that knowledge to the development of a prediction algorithm, and to institute a prevention program at a tertiary medical center.

Methods:

We analyzed SH events for 172 patients and developed computer algorithms to predict SH that were tested on a population of 3028 inpatients who were found to have blood glucose (BG) <90 mg/dl during their hospital stay. Variables with significant bivariate associations were entered into partition analyses to identify interactions. Logistic regression was performed by calculating parameters related to the odds of hypoglycemia below each cut point. Sensitivity and specificity were determined at various cut points. The cut points resulting in 50% sensitivity for each hypoglycemia level were determined. These algorithms were tested against the initial 172 adjudicated patients.

Results:

Variables related to the BG <40 mg/dl cut off point were basal and adjustment scale insulin doses, weight, and creatinine clearance, while variables related to the 60 mg/dl and 70 mg/dl cut points were basal, prandial, and adjustment scale insulin doses, weight, creatinine clearance, and sulfonylurea use. The 50% sensitivity cut point developed using the <70 mg/dl algorithm correctly identified 71% of the adjudicated cases, while the <60 mg/dl and <40 mg/dl algorithms identified 70% and 55% respectively.

Conclusions:

A validated prediction algorithm for SH can aid in the identification of patients at risk for SH and may be useful in the development of prevention strategies.
A Human Pilot Study of the Fluorescence Affinity Sensor for Continuous Glucose Monitoring in Diabetes
Authors: Dutt-Ballerstadt Ralph , Evans Colton , Pillai Arun P. , Orzeck Eric , Drabek Rafal , Gowda Ashok , McNichols Roger
Published: January 2014

Objective:

We report results of a pilot clinical study of a subcutaneous fluorescence affinity sensor (FAS) for continuous glucose monitoring conducted in people with type 1 and type 2 diabetes. The device was assessed based on performance, safety, and comfort level under acute conditions (4 h).

Research Design and Methods:

A second-generation FAS (BioTex Inc., Houston, TX) was subcutaneously implanted in the abdomens of 12 people with diabetes, and its acute performance to excursions in blood glucose was monitored over 4 h. After 30–60 min the subjects, who all had fasting blood glucose levels of less than 200 mg/dl, received a glucose bolus of 75 g/liter dextrose by oral administration. Capillary blood glucose samples were obtained from the finger tip. The FAS data were retrospectively evaluated by linear least squares regression analysis and by the Clarke error grid method. Comfort levels during insertion, operation, and sensor removal were scored by the subjects using an analog pain scale.

Results:

After retrospective calibration of 17 sensors implanted in 12 subjects, error grid analysis showed 97% of the paired values in zones A and B and 1.5% in zones C and D, respectively. The mean absolute relative error between sensor signal and capillary blood glucose was 13% [±15% standard deviation (SD), 100–350 mg/dl] with an average correlation coefficient of 0.84 (±0.24 SD). The actual average “warm-up” time for the FAS readings, at which highest correlation with glucose readings was determined, was 65 (±32 SD) min. Mean time lag was 4 (±5 SD) min during the initial operational hours. Pain levels during insertion and operation were modest.

Conclusions:

The in vivo performance of the FAS demonstrates feasibility of the fluorescence affinity technology to determine blood glucose excursions accurately and safely under acute dynamic conditions in humans with type 1 and type 2 diabetes. Specific engineering challenges to sensor and instrumentation robustness remain. Further studies will be required to validate its promising performance over longer implantation duration (5–7 days) in people with diabetes.