bluuebunny/crossref_metadata_2025 huggingface dataset:
Parenteral Glucose and Glucose Control in the Critically Ill: A Kinetic Appraisal
Authors: Hovorka Roman , Cordingley Jeremy
Published: January 2014

Background:

We investigated the influence of parenteral glucose infusion on insulin-driven tight glucose control (4.4–6.1 mmol/liter) in the critically ill by appraising kinetic characteristics of the glucoregulatory system.

Methods:

Turnover characteristics of the glucoregulatory system associated with constant 0, 1.2, and 2.4 mg/kg/min parenteral glucose infusion were obtained by literature review and mass-balance calculations.

Results:

Without parenteral glucose infusion, the achievement of tight glucose control is hampered by long time delays with an anticipated glucose equilibration half-time ( T1/2) of 185 min. The constant parenteral glucose infusions of 1.2 and 2.4 mg/kg/min reduce T1/2 to 80 and 40 min, respectively. This follows on from the accelerated glucose turnover brought about by the insulin-modulated glucose uptake, which increases in response to increasing exogenous insulin required to achieve tight glucose control. However, large variations exist among glucose turnover characteristics in the critically ill.

Conclusions:

The constant parenteral glucose infusion greater or equal to 2.4 mg/kg/min is expected to simplify the achievement of tight glucose control by reducing system delays and may facilitate the development of more intuitive, efficacious, and safer insulin-titration guidelines.
Telemedicine-Based KADIS® Combined with CGMS™ Has High Potential for Improving Outpatient Diabetes Care
Authors: Salzsieder Eckhard , Augstein Petra , Vogt Lutz , Kohnert Klaus-Dieter , Heinke Peter , Freyse Ernst-Joachim , Ahmed Abdel Azim , Metwali Zakia , Salman Iman , Attef Omer
Published: January 2014

Background:

The Karlsburg Diabetes Management System (KADIS®) was developed over almost two decades by modeling physiological glucose-insulin interactions. When combined with the telemedicine-based communication system TeleDIAB® and a continuous glucose monitoring system (CGMS™), KADIS has the potential to provide effective, evidence-based support to doctors in their daily efforts to optimize glycemic control.

Methods:

To demonstrate the feasibility of improving diabetes control with the KADIS system, an experimental version of a telemedicine-based diabetes care network was established, and an international, multicenter, pilot study of 44 insulin-treated patients with type 1 and 2 diabetes was performed. Patients were recruited from five outpatient settings where they were treated by general practitioners or diabetologists. Each patient underwent CGMS monitoring under daily life conditions by a mobile monitoring team of the Karlsburg diabetes center at baseline and 3 months following participation in the KADIS advisory system and telemedicine-based diabetes care network. The current metabolic status of each patient was estimated in the form of an individualized “metabolic fingerprint.” The fingerprint characterized glycemic status by KADIS-supported visualization of relationships between the monitored glucose profile and causal endogenous and exogenous factors and enabled evidence-based identification of “weak points” in glycemic control. Using KADIS-based simulations, physician recommendations were generated in the form of patient-centered decision support that enabled elimination of weak points. The analytical outcome was provided in a KADIS report that could be accessed at any time through TeleDIAB. The outcome of KADIS-based support was evaluated by comparing glycosylated hemoglobin (HbAlc) levels and 24-hour glucose profiles before and after the intervention.

Results:

Application of KADIS-based decision support reduced HbAlc by 0.62% within 3 months. The reduction was strongly related to the level of baseline HbA1c, diabetes type, and outpatient treatment setting. The greatest benefit was obtained in the group with baseline HbAlc levels >9% (1.22% reduction), and the smallest benefit was obtained in the group with baseline HbA1c levels of 6–7% (0.13% reduction). KADIS was more beneficial for patients with type 1 diabetes (0.79% vs 0.48% reduction) and patients treated by general practitioners (1.02% vs 0.26% reduction). Changes in HbA1c levels were paralleled by changes in mean daily 24-hour glucose profiles and fluctuations in daily glucose.

Conclusion:

Application of KADIS in combination with CGMS and the telemedicine-based communication system TeleDIAB successfully improved outpatient diabetes care and management.
Does Needle Size Matter?
Authors: Gill Harvinder S. , Prausnitz Mark R.
Published: January 2014

Hypodermic needles are in widespread use, but patients are unhappy with the pain, anxiety, and difficulty of using them. To increase patient acceptance, smaller needle diameters and lower insertion forces have been shown to reduce the frequency of painful injections. Guided by these observations, fine needles and microneedles have been developed to minimize pain and have found the greatest utility for delivery of vaccines and biopharmaceuticals such as insulin. However, pain reduction must be balanced against limitations of injection depth, volume, and formulations introduced by reduced needle dimensions. In some cases, needle-free delivery methods provide useful alternatives.
Comparing the Performance of the Optical Glucose Assay Based on Glucose Binding Protein with High-Performance Anion-Exchange Chromatography with Pulsed Electrochemical Detection: Efforts to Design a Low-Cost Point-of-Care Glucose Sensor
Authors: Ge Xudong , Lam Hung , Modi Swati J. , LaCourse William R. , Rao Govind , Tolosa Leah
Published: January 2014

Background:

The glucose binding protein (GBP) is one of many soluble binding proteins found in the periplasmic space of gram-negative bacteria. These proteins are responsible for chemotactic responses and active transport of chemical species across the membrane. Upon ligand binding, binding proteins undergo a large conformational change, which is the basis for converting these proteins into optical biosensors.

Methods:

The GBP biosensor was prepared by attaching a polarity-sensitive fluorescent probe to a single cysteine mutation at a site on the protein that is allosterically responsive to glucose binding. The fluorescence response of the resulting sensor was validated against high-performance anion-exchange chromatography (HPAEC) with pulsed electrochemical detection. Finally, a simple fluorescence reader was built using a lifetime-assisted ratiometric technique.

Results:

The GBP assay has a linear range of quantification of 0.100–2.00 μM and a sensitivity of 0.164 μM−1 under the specified experimental conditions. The comparison between GBP and HPAEC readings for nine blind samples indicates that there is no statistical difference between the analytical results of the two methods at the 95% confidence level. Although the methods of fluorescence detection are based on different principles, the response of the homemade device to glucose concentrations was comparable to the response of the larger and more expensive tabletop fluorescence spectrophotometer.

Conclusions:

A glucose binding protein labeled with a polarity-sensitive probe can be used for measuring micromolar amounts of glucose. Using a lifetime-assisted ratiometric technique, a low-cost GBP-based micromolar glucose monitor could be built.
Polarization-Based Diffuse Reflectance Imaging for Noninvasive Measurement of Glucose
Authors: Cameron Brent D. , Li Yanfang
Published: January 2014

Background:

The ability to measure glucose concentration through noninvasive approaches would impact the treatment of diabetes significantly. Polarization-based optical approaches have received considerable interest because of their potential medical applications. Glucose, a chiral molecule, has the ability to rotate the plane of linearly polarized light, commonly referred to as optical activity, as well as changing the refractive index of the media, which therefore affects the overall scattering coefficient in a given media. The magnitude of each effect is related to the concentration of glucose. Although most previous studies have reported on the use of polarimetry in the aqueous humor of the eye because of its nonscattering nature, one would also expect that glucose concentration could be measured in more turbid media such as tissue through a similar approach. This study investigated how each of these effects is correlated to glucose concentration in a physiological range for highly scattering biological media.

Methods:

A custom-designed imaging polarimeter was used to image highly scattering Intralipid-based media containing different concentrations of glucose. Model formation and glucose prediction were performed through the use of partial least squares (PLS) regression. Further insight into the differences between polarization-based image measurements and encoding of glucose information was provided through the use of principal component analysis (PCA).

Results:

When coupled with PLS regression, in vitro polarization measurements yielded highly correlated glucose predictions in both calibration and independent validation, 0.999 and 0.998, respectively. Through the use of PCA, it appears that the majority of the image-based signal yielding the most significant glucose information is attributable to changes in the overall scattering coefficient due to glucose concentration and, to a lesser degree, effects of optical activity.

Conclusions:

This study showed how polarimetric-based imaging coupled with PLS regression can be used to quantify glucose concentration in highly scattering media. Such methods may potentially be able to extend the use of noninvasive in vivo polarimetric measurements, normally acquired in the anterior chamber of the eye, to other preferred sensing sites such as the skin.
Analysis of the Roles of “Serious Games” in Helping Teach Health-Related Knowledge and Skills and in Changing Behavior
Authors: Lewis Matthew W.
Published: January 2014

Researchers are developing sophisticated games specifically targeted to teach health-related knowledge and skills and to change health-related behaviors. Although these interventions, generally called “serious games,” show promise, there has been limited evaluation of their effectiveness. This article offers a broad “consumer guide” for evaluating such health education interventions. Improving the development and evaluation of health-related serious games and educating potential purchasers of such products to be knowledgeable, demanding consumers will help move the field of serious games from “looks promising” to determining where such interventions will be effective and where they will not.
Noninvasive Glucose Monitoring Systems: Will We Ever Have Such Sensors for Practical Use?
Authors: Heinemann Lutz
Published: January 2014

It is still the dream of patients with diabetes and diabetologists to be able to monitor glucose changes in the human body over prolonged periods of time without hurting the patients, i.e. without having the need to break the skin barrier. This commentary tries to highlight why we should invest more brain power and money in this area of research while also raising the following critical question: Can we be sure that a reliable system for noninvasive glucose monitoring will ever be possible? Finally, I propose establishing an international working group for glucose monitoring. Such an independent group of researchers (which would not focus on noninvasive approaches only) might be very instrumental in bringing a critical and constructive approach in this area of research forward.
Complication Reducing Effect of the Information Technology-Based Diabetes Management System on Subjects with Type 2 Diabetes
Authors: Cho Jae-Hyoung , Lee Jin-Hee , Oh Jeong-Ah , Kang Mi-Ja , Choi Yoon-Hee , Kwon Hyuk-Sang , Chang Sang-Ah , Cha Bong-Yun , Son Ho-Young , Yoon Kun-Ho
Published: January 2014

Objective:

We introduced a new information technology-based diabetes management system, called the Internet-based glucose monitoring system (IBGMS), and demonstrated its short-term and long-term favorable effects. However, there has been no report on clinical effects of such a new diabetes management system on the development of diabetic complications so far. This study was used to simulate the complication reducing effect of the IBGMS, given in addition to existing treatments in patients with type 2 diabetes.

Research Design and Methods:

The CORE Diabetes Model, a peer-reviewed, published, validated computer simulation model, was used to project long-term clinical outcomes in type 2 diabetes patients receiving the IBGMS in addition to their existing treatment. The model combined standard Markov submodels to simulate the incidence and progression of diabetes-related complications.

Results:

The addition of IBGMS was associated with improvements in reducing diabetic complications, mainly microangiopathic complications, including diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and diabetic foot ulcer. The IBGMS also delayed the development of all diabetic complications for more than 1 year.

Conclusions:

This study demonstrated that the simulated IBGMS, compared to existing treatment, was associated with a reduction of diabetic complications. As a result, it provides valuable evidence for practical application to the public in the world.
Telemedicine and Diabetes Management: Current Challenges and Future Research Directions
Authors: Bellazzi Riccardo
Published: January 2014

Telemedicine is lying between fading and future. Several clinical studies and critical reviews have been published recently, but the results are inconclusive and the adoption of telemedicine interventions in clinical practice is slow. This article discusses some of the current problems related to the adoption of telemedicine systems and focuses on the information technology solutions that appear to be most promising for diabetes management in the near future. Context awareness, user modeling, intelligent dialogues, and integrated information systems are presented. Some potential future scenarios for the adoption of telemedicine, which combine novel technologies and new organizational models, are also discussed. Within those scenarios, telemedicine may prove to be a good instrument to support health care providers in the effective management and prevention of diabetes mellitus.
Diabetologists' and Patients' Views on Continuous Glucose Monitoring: Do They Talk about the Same Story?
Authors: Heinemann Lutz
Published: January 2014

As clinicians, we believe that patients with diabetes have the same views on continuous glucose monitoring that we have. For them, however, the focus is not optimization of metabolic control, but living a life that is as normal as possible. This difference can become an issue in clinical trials of systems for continuous glucose monitoring. If such systems demonstrate no benefit to metabolic control over standard spot capillary glucose monitoring, does this really reflect an insufficient efficacy of the continuous glucose monitoring system tested or is this the result of a “conflict of interest?” This commentary contemplates the mismatch in aims that might lead to such study results. From my point of view, it is critical to find a solution to this issue, as otherwise the benefits of continuous glucose monitoring (which I believe in quite strongly) cannot be shown in a manner that convinces health care payers to reimburse these new technologies on a broader scale.
Physical Activity—The Major Unaccounted Impediment to Closed Loop Control
Authors: Breton Marc D.
Published: January 2014

This article presents a mathematical model of glucose homeostasis that is valid during physical activity. Known changes in glucose dynamics during exercise were accounted for in the model, and exercise itself was detected and quantified through heart rate (beats per minute). The model was successfully fit to 21 type 1 diabetic subjects during a hyperinsulemic clamp protocol, and performance of the new model was compared with the standard minimal model of glucose kinetics that it was derived from.
Impact of Islet Transplantation on Glycemic Control as Evidenced by a Continuous Glucose Monitoring System
Authors: Gorn Lisa , Faradji Raquel N. , Messinger Shari , Monroy Kathy , Baidal David A. , Froud Tatiana , Mastrototaro John , Ricordi Camillo , Alejandro Rodolfo
Published: January 2014

Background:

This study evaluated the effects of islet allotransplantation (ITx) on metabolic control utilizing a continuous glucose monitoring system (CGMS) and assessed its effectiveness as an indicator and predictor of graft dysfunction (GD).

Methods:

Glycemic control was assessed in 25 patients with type 1 diabetes mellitus (T1DM); 12 ITx recipients and 13 controls. Mean interstitial glucose, standard deviation (SD), glucose variability, and percentage of time in hyperglycemia (%GT >140 mg/dl), hypoglycemia (%GT <54 mg/dl), and normoglycemia (%GT 54–140 mg/dl) were measured in 72-hour time periods from CGMS recordings in the control group at baseline and in the ITx group at 3, 6, 9, 12, 15, and 18 months after ITx completion and were analyzed as predictors and indicators of GD. Hemoglobin A1c (HbA1c), 90-minute glucose after a mixed meal tolerance test, fasting C-peptide/glucose ratio, and insulin requirements were followed.

Results:

Compared to the control group, the percentage of time in hypoglycemia was significantly lower in the ITx group at all time points; time in normoglycemia was increased at all times except at 15 months; and time in hyperglycemia was significantly lower at 6, 9, 12, and 18 months. Mean glucose and glucose variability were significantly lower in the ITx group at all times except at 3 and 15 months, whereas HbA1c and 90-minute glucose were significantly lower in the ITx group at all time points. Mean glucose, SD, glucose variability, and %GT >140 mg/dl were significant as indicators but not as predictors of GD.

Conclusions:

The CGMS demonstrated the benefits of ITx in T1DM, with improvements in glycemic control apparent up to 18 months after transplant. CGMS measures were found to be indicators of GD.
Noninvasive Transcutaneous Sampling of Glucose by Electroporation
Authors: Murthy S. Srinivasa , Kiran V. Siva Ram , Mathur S. K. , Murthy S. Narasimha
Published: January 2014

Background:

In people with diabetes, blood glucose levels should be monitored regularly to prevent serious complications associated with diabetes. This involves the invasive method of withdrawing blood, which causes inconvenience to patients. The objective of this study was to investigate the efficiency of the noninvasive electroporation and transcutaneous sampling (ETS) technique for predicting blood glucose levels.

Methods:

In vitro studies were carried out in Franz diffusion cells using porcine epidermis to assess the feasibility of transcutaneous sampling of glucose. In vivo, the ETS technique was assessed in the diabetes-induced Sprague—Dawley rat model. Glucose was sampled following the application of 30 electrical pulses of 1 ms duration at 120V/cm2, 1 Hz. Clarke error grid analysis was carried out for the venous blood glucose levels that were determined by the ETS with reference to those measured by a glucose meter.

Results:

The amount of glucose sampled by the ETS method both in vitro and in vivo was proportional to the dermal glucose concentration. All data points from in vivo studies were in A and B zones of Clarke error grid analysis, and the mean absolute relative error was 12.8%.

Conclusion:

Results of the present study demonstrate that ETS technique could be developed as a noninvasive method of predicting venous blood glucose levels in people with diabetes.
Design as a Critical Tool in Bariatric Patient Care
Authors: Wignall Doug
Published: January 2014

Both men and women in the United States are roughly an inch taller and 25 pounds heavier than they were in 1960, says the National Center for Health Statistics at the Centers for Disease Control and Prevention. An increasing number are also overweight or obese. In fact, obesity has become an alarming epidemic with enormous implications for our health care system. A critical concern is the ability to care physically and emotionally for this segment of the patient population. Respecting patient dignity and delivering optimum clinical care are primary issues, as are establishing procedures for safeguarding the health and well-being of these patients and their caregivers. Design is a critical tool in the care of and the improved long-term clinical outcomes for bariatric patients; success mandates a three-prong approach to the design process: appropriate facilities and space, proper equipment and furnishings, and training and standardized care protocols. Together, these components ensure the ability of a health care provider to adequately care for all patients—including this newest and rapidly growing patient segment—with equality and dignity.
Blood Glucose Meters That Are Accessible to Blind and Visually Impaired Persons
Authors: Uslan Mark M. , Burton Darren M. , Clements Charles W.
Published: January 2014

Blood glucose meters (BGMs) that can be used nonvisually or with a visual limitation were introduced in the mid-1990s, but it was not until 2006 and 2007 that a new set of meters with accessibility features were introduced: Prodigy, Prodigy Autocode, and Prodigy Voice (Diagnostic Devices, Charlotte, NC), and Advocate and Advocate Redi-Code (TaiDoc, Taiwan). Accessibility attributes of the newly introduced BGMs were tabulated, and product design features were examined and documented. The Prodigy Voice was found to be the only one of these new BGMs that is fully usable by blind and visually impaired persons.
Clinical Overview of Continuous Glucose Monitoring
Authors: Buckingham Bruce
Published: January 2014

Continuous glucose monitoring (CGM) is now available from several companies in the United States for purchase or research studies. This article provides an overview of these devices and reviews the use of sensors for managing diabetes in “real time,” as well as the use of retrospective analysis of CGM results.
Inhaled Insulin: Promises and Concerns
Authors: Sélam Jean-Louis
Published: January 2014

Since the introduction of Pfizer Exubera® in the early 1990s, a number of other inhaled insulin solutions have been developed. This article provides an overview of inhaled insulin systems developed by Pfizer, Novo Nordisk, MannKind, and Lilly, three of which are currently in phase 3 trials. The strengths and weaknesses of each product, as well as the general technologies (liquid vs dry powder), are evaluated. Results of clinical studies conducted by Pfizer and corroborated by other studies are summarized. Although inhaled insulin promises much, a greater body of controlled studies is necessary to draw firm conclusions about its safety and
Laboratory-Based Non-Clinical Comparison of Occlusion Rates Using Three Rapid-Acting Insulin Analogs in Continuous Subcutaneous Insulin Infusion Catheters Using Low Flow Rates
Authors: Kerr David , Morton John , Whately-Smith Caroline , Everett Joan , Begley Joe P.
Published: January 2014

Background:

Rapid-acting analog insulin is used increasingly for continuous subcutaneous insulin infusion therapy (CSII). As the choice of insulin may be a determinant of catheter occlusion, we compared rates of early and late occlusion of a standard CSII catheter with three insulin analogs in a laboratory-based setting.

Methods:

Twenty-four pumps were used for the study. Each insulin analog (glulisine, lispro, and aspart) was assigned to eight pumps in a randomized order for each of nine runs of 5-day duration. Pumps were primed to receive a basal dose of 0.1 IU/h with a bolus dose of 2 IU given three times each day. Pumps were placed in an incubator to maintain temperature in the range of 32 to 36 °C.

Results:

Over the entire study period, there were 48 occlusions. Early occlusions (within 72 hours) occurred during five of the nine runs with no evidence of any difference between insulins ( p = .27); there were no occlusions before 48 hours. Over the whole of the 5-day infusion period, the probabilities of overall occlusion for each insulin were 40.9% [28 to 55%, 95% confidence interval (CI)] for glulisine, 9.2% (4 to 19.5%, 95% CI) for aspart, and 15.7% (8.1 to 28.1%, 95% CI) for lispro. All occlusions, except for three, occurred during a bolus infusion.

Conclusions:

During CSII under laboratory conditions, early catheter occlusions (within 72 hours) are rare and independent of the choice of insulin analog. For patients using insulin pump therapy, the importance of catheter change within 72 hours should be emphasized irrespective of the insulin used. Beyond 72 hours, the risk of occlusion differs between insulins, being more common with glulisine.
Analysis of Insulin Pen Devices for the Treatment of Diabetes Mellitus
Authors: Thurman Jerome E.
Published: January 2014

Insulin pen devices allow for accurate, flexible, and less complicated delivery of insulin for the treatment of diabetes mellitus. These devices permit small dose administration, and can be used by patients with limited dexterity and visual impairment. These characteristics may prove beneficial when considering their usefulness. The article by Hanel et al. in this issue of Journal of Diabetes Science and Technology clearly points out that the OptiClik® reusable pen may underdose insulin early after cartridge replacement unless properly primed. Insulin pens clearly offer several advantages over traditional vials and syringes. However, patients must be well educated in their use, with continued communication between them and their health care provider to enable good glycemic control.
Optimum Subcutaneous Glucose Sampling and Fourier Analysis of Continuous Glucose Monitors
Authors: Breton Marc D. , Shields Devin P. , Kovatchev Boris P.
Published: January 2014

Background:

The objective of this article was to focus on the application of harmonic decomposition to continuous glucose monitor (CGM) measurements. We show evidence of an attenuation of fast variations of interstitial glucose when compared to blood in type 1 diabetes mellitus (T1DM) and, using information theory, propose optimal sampling schedules associated with the use and study of CGMs.

Method:

Using a cohort of 26 T1DM subjects, wearing two Navigator™ sensors for 1 to 3 days, we analyzed the frequency content of each glucose signal and derived across subject frequency cutoffs using discrete Fourier transform and common signal processing techniques.

Results:

We observed a significant difference in the frequency content of blood glucose compared to interstitial glucose in T1DM, providing evidence toward the existence of a diffusion process between blood and interstitial glucose, acting as a low-pass filter. Furthermore, we obtained a 15-minutes sampling schedule for optimal comparison of CGM values to blood reference.

Conclusion:

Blood glucose and interstitial glucose have different dynamics, as shown by harmonic analysis, and these differences have consequences on advisable schedules for accuracy studies of CGMS.
The Failure of Exubera: Are We Beating a Dead Horse?
Authors: Heinemann Lutz
Published: January 2014

Inhalation of insulin appears to have become an alternative for the subcutaneous injection of insulin for the time being. However, the recent withdrawal of one product that had already reached the marketplace or others that were close to approval raised severe concerns about the future of the pulmonary route for insulin administration. In view of the progress made with respect to the size of the inhaler and the many other options that would improve the pharmacodynamic properties of inhaled insulin, patient acceptance of this innovative approach, and (hopefully) a reduction in cost, we should begin with an open discussion about the future of inhaled insulin in order to avoid its premature death. This commentary discusses many of the advantages and disadvantages of inhaled insulin from the view of the patients, diabetologists, scientists, pharmaceutical industry, health care payers, and politicians. It is hoped that this unusual approach allows keeping an open mind about this interesting route of drug administration.
Predicted Blood Glucose from Insulin Administration Based on Values from Miscoded Glucose Meters
Authors: Raine Charles H. , Pardo Scott , Parkes Joan Lee
Published: January 2014

Objectives:

The proper use of many types of self-monitored blood glucose (SMBG) meters requires calibration to match strip code. Studies have demonstrated the occurrence and impact on insulin dose of coding errors with SMBG meters. This paper reflects additional analyses performed with data from Raine et al. (JDST, 2:205–210, 2007). It attempts to relate potential insulin dose errors to possible adverse blood glucose outcomes when glucose meters are miscoded.

Methods:

Five sets of glucose meters were used. Two sets of meters were autocoded and therefore could not be miscoded, and three sets required manual coding. Two of each set of manually coded meters were deliberately miscoded, and one from each set was properly coded. Subjects ( n = 116) had finger stick blood glucose obtained at fasting, as well as at 1 and 2 hours after a fixed meal (Boost®; Novartis Medical Nutrition U.S., Basel, Switzerland). Deviations of meter blood glucose results from the reference method (YSI) were used to predict insulin dose errors and resultant blood glucose outcomes based on these deviations.

Results:

Using insulin sensitivity data, it was determined that, given an actual blood glucose of 150–400 mg/dl, an error greater than +40 mg/dl would be required to calculate an insulin dose sufficient to produce a blood glucose of less than 70 mg/dl. Conversely, an error less than or equal to −70 mg/dl would be required to derive an insulin dose insufficient to correct an elevated blood glucose to less than 180 mg/dl. For miscoded meters, the estimated probability to produce a blood glucose reduction to less than or equal to 70 mg/dl was 10.40%. The corresponding probabilities for autocoded and correctly coded manual meters were 2.52% ( p < 0.0001) and 1.46% ( p < 0.0001), respectively. Furthermore, the errors from miscoded meters were large enough to produce a calculated blood glucose outcome less than or equal to 50 mg/dl in 42 of 833 instances. Autocoded meters produced zero (0) outcomes less than or equal to 50 mg/dl out of 279 instances, and correctly coded manual meters produced 1 of 416.

Conclusions:

Improperly coded blood glucose meters present the potential for insulin dose errors and resultant clinically significant hypoglycemia or hyperglycemia. Patients should be instructed and periodically reinstructed in the proper use of blood glucose meters, particularly for meters that require coding.
Pilot Studies of Transdermal Continuous Glucose Measurement in Outpatient Diabetic Patients and in Patients during and after Cardiac Surgery
Authors: Chuang Han , Trieu My-Quyen , Hurley James , Taylor Elizabeth J. , England Michael R. , Nasraway Stanley A.
Published: January 2014

Background:

We tested the hypothesis that glucose can be measured continuously and reliably in patients in diverse settings using a transdermal biosensor coupled to a permeated skin site. In addition, we compared a novel, abrasion-based skin permeation method to an ultrasound-based method for transdermal continuous glucose monitoring.

Method:

Transdermal continuous glucose monitors were applied to patients with diabetes (study I), patients undergoing cardiac surgery (study II), and healthy volunteers (study III). Reference blood glucose measurements were performed with glucometers or standard blood glucose analyzers. At the conclusion of the 24-hour study, data were postprocessed for comparison with the reference blood glucose values collected during the study period.

Results:

Data were validated for 10 subjects for 12 hours in study I, 8 subjects for 24 hours in study II, and 6 subjects in study III. The transdermal continuous glucose monitors usually required 1 hour of warm up. Depending on the study setting, single or multiple calibrations were applied to the datasets. Comparing predicted glucose versus reference blood glucose values, we found that study I yielded 89.6% in zone A and 9.0% in zone B in the Clarke error grid (222 data points), study II yielded 86.4% in zone A and 13.6% in zone B (147 data points), and study III yielded 89.9% in zone A and 10.1% in zone B (378 data points).

Conclusions:

Continuous transdermal glucose monitoring was demonstrated successfully in diverse clinical settings. The performance of abrasion was equivalent to ultrasound skin permeation methodology for transdermal glucose monitoring.
Biocompatibility and Immune Acceptance of Adult Porcine Islets Transplanted Intraperitoneally in Diabetic NOD Mice in Calcium Alginate Poly-L-lysine Microcapsules versus Barium Alginate Microcapsules without Poly-L-lysine
Authors: Safley Susan A. , Cui Hong , Cauffiel Sean , Tucker-Burden Carol , Weber Collin J.
Published: January 2014

Background:

If alginate microcapsules are to be used clinically for therapeutic cell transplants, capsule formulations must be designed to enhance optimal biocompatibility and immune acceptance.

Methods:

Microcapsules were generated using highly purified, endotoxin-free, ultra-low viscosity, high mannuronic acid alginate. The capsules differed with respect to gelling cation (50 m M barium or 100 m M calcium), alginate concentration (2.0% or 3.3%), alginate density (homogeneous or inhomogeneous), and the presence or absence poly-L-lysine (PLL) coating. Four types of empty capsules were implanted intraperitoneally (i.p.) in normal NOD mice, and their biocompatibility was evaluated after various time periods in vivo. Encapsulated adult porcine islets (APIs) were transplanted i.p. in diabetic NOD mice, and immune acceptance was evaluated by graft survival times, host cell adherence to capsule surfaces, and flow cytometric analysis of peritoneal host cells.

Results:

All empty alginate capsules were biocompatible in vivo, but barium-gelled alginate capsules without PLL were clearly the most biocompatible, since 99% of these empty capsules had no host cell adherence up to 9 months in vivo. In diabetic NOD mice, APIs functioned significantly longer in barium-alginate capsules without PLL than in calcium-alginate capsules with PLL and had strikingly less host cell adherence, although large numbers of host cells (predominantly macrophages and eosinophils) infiltrated the peritoneal cavities of recipients with APIs in both types of capsules. Addition of PLL coatings to barium-alginate capsules dramatically decreased graft survival.

Conclusions:

Inhomogeneous barium-gelled alginate capsules without PLL are the optimal candidates for clinical trials, based on their enhanced biocompatibility and immune acceptance in vivo.
A Review of the Foreign-body Response to Subcutaneously-implanted Devices: The Role of Macrophages and Cytokines in Biofouling and Fibrosis
Authors: Ward W. Kenneth
Published: January 2014

The biological response to implanted biomaterials in mammals is a complex series of events that involves many biochemical pathways. Shortly after implantation, fibrinogen and other proteins bind to the device surface, a process known as biofouling. Macrophages then bind to receptors on the proteins, join into multinucleated giant cells, and release transforming growth factor β and other inflammatory cytokines. In response to these signals, quiescent fibroblasts are transformed into myofibroblasts, which synthesize procollagen via activation of Smad mediators. The procollagen becomes crosslinked after secretion into the extracellular space. Mature crosslinked collagen and other extracellular matrix proteins gradually contribute to formation of a hypocellular dense fibrous capsule that becomes impermeable or hypopermeable to many compounds. Porous substrates and angiogenic growth factors can stimulate formation of microvessels, which to some extent can maintain analyte delivery to implanted sensors. However, stimulation by vascular endothelial growth factor alone may lead to formation of leaky, thin-walled, immature vessels. Other growth factors are most probably needed to act upon these immature structures to create more robust vessels.

During implantation of foreign bodies, the foreign-body response is difficult to overcome, and thousands of biomaterials have been tested. Biomimicry (i.e., creating membranes whose chemical structure mimics natural cellular compounds) may diminish the response, but as of this writing, it has not been possible to create a stealth material that circumvents the ability of the mammalian surveillance systems to distinguish foreign from self.
An Analysis of the Assessment of Glycated Hemoglobin Using A1cNow+™ Point-of-Care Device Compared to Central Laboratory Testing—an Important Addition to Pharmacist-Managed Diabetes Programs?
Authors: Carter Alan W.
Published: January 2014

The diabetes epidemic is accelerating rapidly. If no progress is made in early detection, then early intervention and treatment-to-goal diabetes care will become an overwhelming burden on our health care system. Better utilization of self-monitoring of blood glucose in patients with type 2 diabetes not on insulin could be achieved with regular review of hemoglobin A1c (A1C) values. Educating patients about the importance of diet, exercise, and medication compliance is enhanced when evidence of average blood glucose control can be presented to the patient directly. Affordable, accurate point-of-care testing of A1C with A1cNow+™ (Bayer HealthCare, Terrytown, NY) utilized in pharmacist-managed outpatient diabetes programs may prove to be an important clinical tool for improving patient outcomes and reducing the cost of the expanding diabetes epidemic.
Modular Artificial β-Cell System: A Prototype for Clinical Research
Authors: Dassau Eyal , Zisser Howard , Palerm Cesar C. , Buckingham Bruce A. , Jovanovič Lois , Doyle Francis J.
Published: January 2014

Background:

The quest toward an artificial β-cell has been accelerating, propelled by recent technological advances in subcutaneous glucose sensors and insulin pumps. The development and clinical testing of algorithms involves several challenges: communication and data transfer between a sensor and a pump via computer, a human interface presenting real-time information to the physician, safety issues when an automated system is used to administer insulin, and an architecture that supports different sensors, pumps, and control algorithms. These challenges were addressed in the development of a modular artificial β-cell system for clinical research.

Methods:

The developmental environment of MATLAB® (The MathWorks, Inc., Natick, MA) allowed the flexible implementation of communication protocols for different sensors and pumps. The system has a plug-and-play option for the control algorithm and a human interface that presents and logs the data, enforces protocol safety rules, and facilitates physician oversight.

Results:

A novel platform for use in clinical research trials was realized as a bridge toward a portable unit. This prototype encapsulates communication between the control algorithm, the pump, and the sensors. Its intuitive human interface presents all the relevant patient information to the physician and allows events to be electronically logged. It facilitates subject safety by way of integrated interlocks, checklists, and alarms.

Conclusion:

The modular design of the system allows for the robust testing of various sensors and pumps as well as feedback control, meal detection, predictive hypoglycemia alarms, and device-related algorithms to detect sensor or pump failure.
Real-Time Continuous Glucose Monitoring in the Clinical Setting: The Good, the Bad, and the Practical
Authors: Mamkin Irene , Ten Svetlana , Bhandari Sonal , Ramchandani Neesha
Published: January 2014

Real-time continuous glucose monitoring (RT-CGM) is the latest technological breakthrough in diabetes care. Despite its limitations of lag time between sensor and blood glucose, the need for calibration, false detection of and failure to detect hypoglycemia, and mild discomfort or skin irritation reported in some users, RT-CGM is a highly beneficial tool that can be used to detect nocturnal or unrecognized hypoglycemia and glycemic variability. This, in turn, can lead to better treatment decisions, which may improve metabolic control and decrease the incidence and progression of diabetes complications. The RT-CGM devices are fairly accurate and easy to use. It is not difficult to establish a clinical RT-CGM program in the office. However, it requires persistence and an understanding of the patient's perspective of using RT-CGM so it can be presented and taught appropriately. This article discusses the benefits and limitations of RT-CGM and establishment of a RT-CGM program in the clinical setting.
Electrical Stimulation of the Gut for the Treatment of Type 2 Diabetes: The Role of Automatic Eating Detection
Authors: Policker Shai , Lu Hongli , Haddad Walid , Aviv Ricardo , Kliger Anat , Glasberg Offer , Goode Paul
Published: January 2014

Background:

Automatic eating detection (AED) can potentially support treatments that need to be synchronized with food intake. This article analyzes an implantable AED device working in conjunction with gastric stimulation intended to treat type 2 diabetes (T2DM). The device continuously senses for changes in tissue impedance and electrical activity induced by food intake and initiates treatment sessions upon detection. This article reviews AED performance as well as its relevance to treatment outcomes.

Methods:

Obese T2DM ( n = 12) were implanted with gastric leads and the TANTALUS® device. An AED algorithm was embedded in the device and was used to initiate periods of electrical stimulation during food intake. AED performance was assessed using patients' food diaries. The treatment outcome at 37 weeks postimplants was correlated with the rates of stimulation during large meals vs stimulation during periods of no caloric intake.

Results:

The algorithm was able to detect 73% of meals consumed while sensing. The rate of false stimulations was 28%. Stimulation during meals was significantly correlated ( R2 = 0.45, p < 0.05) with hemoglobin A1c change (average drop in hemoglobin A1c was −1 ± 0.4%) but not with changes in body weight (average drop −4.7 ± 2.8 kg). Stimulation during periods with no caloric intake was negatively correlated with hemoglobin A1c reduction ( R2 = 0.27, p < 0.05).

Conclusions:

Sensing of gastric activity can be used for detection of food intake. The synchronization of gastric stimulation to periods of food intake is correlated with metabolic outcomes. AED may also benefit other applications such as drug delivery and control of food restriction devices.
Drugs in the Pipeline for the Obesity Market
Authors: Klonoff David C. , Greenway Frank
Published: January 2014

Obesity is a major public health problem. For many obese patients, diet and exercise are an inadequate treatment and bariatric surgery may be too extreme of a treatment. As with many other chronic diseases, pharmacologic treatment may be an attractive option for selected obese patients. Antiobesity drugs may potentially work through one of three mechanisms: (1) appetite suppression, (2) interference with absorption of nutrients, and (3) increased metabolism of nutrients. The three most widely prescribed drugs approved to treat obesity are phentermine, sibutramine, and orlistat. Drugs approved for treating obesity usually result in an additional weight loss of approximately 2–5 kg in addition to placebo. For pharmacologic therapy in obesity to be widely utilized, greater effectiveness and safety will be needed. Four types of single-agent drugs are in late stage development, including (1) selective central cannabinoid-1 receptor blockers, (2) selective central 5-hydroxytryptamine 2C serotonin receptor agonists, (3) an intestinal lipase blocker, and (4) central-acting incretin mimetic drugs. Four combination agent compounds in late stage development include (1) Contrave, which combines long-acting versions of naltrexone and bupropion; (2) Empatic, which combines long-acting bupropion and long-acting zonisamide; (3) Qnexa, which combines phentermine with controlled release topiramate; and (4) an injectable combination of leptin and pramlintide. Peptide YY and melanin-concentrating hormone receptor-1 antagonists are centrally acting agents in early stage development. It is expected that several new drug products for obesity will become available over the next few years. Their role in managing this disease remains to be determined.
Blood Glucose Measurements in Arterial Blood of Intensive Care Unit Patients Submitted to Tight Glycemic Control: Agreement between Bedside Tests
Authors: Van Vlasselaers Dirk , Herpe Tom , Milants Ilse , Eerdekens Mona , Wouters Pieter J. , De Moor Bart , Van den Berghe Greet
Published: January 2014

Background:

Implementing tight glycemic control (TGC) in intensive care unit (ICU) patients requires accurate blood glucose (BG) monitoring. We evaluated the performance of two commercially available bedside glucometers, Accu-Chek® and HemoCue®, in patients admitted to the ICU and in whom TGC was applied.

Methods:

Thirty-seven adult ICU patients were prospectively included. During 48 hours, BG was determined simultaneously on the same arterial blood sample using the two point-of-care testing (POCT) glucometers as compared with the standard technique. Data of 452 paired measurements were analyzed using linear regression, Clark error grid analysis (EGA), the method of Bland-Altman, and the GLYCENSIT procedure.

Results:

Both tested glucometers showed satisfactory results when evaluated with linear regression and EGA. Correlation coefficients were above 0.9, and 100% of all the glucose readings were within the safe zones A and B using EGA. However, when applying more appropriate tests, both sensors failed to provide sufficient accuracy in the setting of TGC in ICU patients. The Hemocue revealed a bias of >10 mg/dl with a trend to systematically overestimate the actual BG value. The bias for the Accu-Chek was 6 mg/dl with wide limits of agreement and a variable over- and underestimation of the actual BG value depending on the level of BG (hypo-, normo-, or hyperglycemia).

Conclusions:

When TGC is implemented in ICU practice, caution is warranted when adjusting insulin rates based only on BG readings obtained by the tested glucometers. ICU practitioners should weigh the advantages and disadvantages of such devices: a greater bias but with a more predictable error and measurement behavior versus a somewhat lower bias but with an unpredictable direction of the difference.