bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
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.
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.
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.
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.
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.