bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Clinical Research Tool: A High-Performance Microdialysis-Based System for Reliably Measuring Interstitial Fluid Glucose Concentration
Authors: Ocvirk Gregor , Hajnsek Martin , Gillen Ralph , Guenther Arnfried , Hochmuth Gernot , Kamecke Ulrike , Koelker Karl-Heinz , Kraemer Peter , Obermaier Karin , Reinheimer Cornelia , Jendrike Nina , Freckmann Guido 
Published: January 2014

Background: A novel microdialysis-based continuous glucose monitoring system, the so-called Clinical Research Tool (CRT), is presented. The CRT was designed exclusively for investigational use to offer high analytical accuracy and reliability. The CRT was built to avoid signal artifacts due to catheter clogging, flow obstruction by air bubbles, and flow variation caused by inconstant pumping. For differentiation between physiological events and system artifacts, the sensor current, counter electrode and polarization voltage, battery voltage, sensor temperature, and flow rate are recorded at a rate of 1 Hz. Method: In vitro characterization with buffered glucose solutions (cglucose = 0 − 26 × 10−3 mol liter−1) over 120 h yielded a mean absolute relative error (MARE) of 2.9 ± 0.9% and a recorded mean flow rate of 330 ± 48 nl/min with periodic flow rate variation amounting to 24 ± 7%. The first 120 h in vivo testing was conducted with five type 1 diabetes subjects wearing two systems each. A mean flow rate of 350 ± 59 nl/min and a periodic variation of 22 ± 6% were recorded. Results: Utilizing 3 blood glucose measurements per day and a physical lag time of 1980 s, retrospective calibration of the 10 in vivo experiments yielded a MARE value of 12.4 ± 5.7. Clarke error grid analysis resulted in 81.0%, 16.6%, 0.8%, 1.6%, and 0% in regions A, B, C, D, and E, respectively. Conclusion: The CRT demonstrates exceptional reliability of system operation and very good measurement performance. The ability to differentiate between artifacts and physiological effects suggests the use of the CRT as a reference tool in clinical investigations.
A Cell-Based Approach for Diabetes Treatment Using Engineered Non-β Cells
Authors: Bara Heather , Thulé Peter M. , Sambanis Athanassios 
Published: January 2014

Background: Implantation of insulin-secreting cells has the potential to provide tight glycemic regulation in diabetic subjects. Implantation of cadaveric human islets in immunosuppressed human patients is currently applied at a very small scale. To overcome the limitations of tissue availability and recipient immunosuppression, encapsulation of nonautologous cells and use of potentially autologous nonislet cells, the latter engineered for insulin secretion, are being pursued. This article reports on recent findings with the implantation of tissue constructs containing enteroendocrine cells stably expressing recombinant insulin in diabetic mice. The concept of a dual recombinant hepatic and enteroendocrine cell system, which may better approximate the secretory response of islets, is discussed. Methods: Mouse GLUTag-INS cells engineered to secrete human insulin were developed and incorporated in tissue constructs as reported previously. Constructs were implanted intraperitoneally in diabetic mice, and blood glucose levels, animal weights, and plasma insulin levels were measured at various time points. Results: GLUTag-INS-containing tissue constructs secreted insulin preimplantation and postexplantation, and human insulin was detected in the plasma of diabetic mice. However, normoglycemia was not restored. Conclusions: A variety of cell types and of encapsulation methods to enhance immune acceptance of insulin-secreting grafts are being pursued. Recombinant enteroendocrine cells show promise, but it is likely that they need to be combined with recombinant hepatic cells to achieve glycemic normalization.
Influence of Variables on Hemoglobin A1c Values and Nonheterogeneity of Hemoglobin A1c Reference Ranges
Authors: Higgins Trefor , Cembrowski George , Tran David , Lim Erin , Chan Julie 
Published: January 2014

Introduction: Hemoglobin A1c (HbAlc) values are influenced by analytical interferences such as HbF and hemoglobin variants and clinical factors such as increased red cell turnover. Although less well-known, demographic factors such as race, age, and sex also influence HbA1c values. The HbA1c reference range should be homogenous in the United States based on the use of National Glycohemoglobin Standardization Program certified methods and the recommendations in the National Academy of Clinical Biochemistry guidelines. Methods: Data on age, race, sex, HbA1c, and glucose values were extracted from the National Health and Nutrition Examination study for a 3 year period. A search for reference range data for laboratories in the United States was performed using the Google search engine. Results: Extracted data agree with published data on the influence of age, sex, and smoking status on HbA1c values. There is substantial heterogeneity in HbA1c reference ranges in laboratories in the United States. Conclusion: Age, sex, and smoking status influence HbA1c values. Despite standardization of HbA1c methods and published recommendations, there is wide heterogeneity in HbA1c reference ranges in the United States.
Increases in Whole Blood Glucose Measurements Using Optically Based Self-Monitoring of Blood Glucose Analyzers Due to Extreme Canadian Winters
Authors: Cembrowski George C. , Smith Barbara , O'Malley Ellen M. 
Published: January 2014

Background: Temperature and humidity have been reported to influence the results of whole blood glucose (WBG) measurements. Methods: To determine whether patient WBG values were affected by seasonal variation, we conducted a retrospective analysis of 3 years' worth of weekly averages of patient WBG in five Edmonton hospitals. Results: In all five hospitals, the winter WBG averages were consistently higher than the summer WBG averages, with the differences varying between 5% and 9%. Whole blood glucose averages were negatively correlated with the outside temperature. This seasonal variation was not observed in weekly patient averages of specimens run in a central hospital laboratory. Interpretation It is probable that the seasonal variation of WBG arises from the very low indoor humidities that are associated with external subzero temperatures. These increases in WBG in cold weather may be due to limitations in the WBG measuring systems when operated in decreased humidities and/or increased evaporation of the blood sample during the blood glucose measurement process. The implications of this seasonal variation are significant in that it (1) introduces increased variability in patient WBG, (2) may result in increased glucose-lowering therapy during periods of external cold and low indoor humidity, and (3) confounds evaluations of WBG meter technology in geographic regions of subzero temperature and low indoor humidity. To mitigate the risk of diagnosing and treating factitious hyperglycemia, the humidity of patient care areas must be strictly controlled.
Seasonal Variation in Hemoglobin A1c: Is It the Same in Both Hemispheres?
Authors: Higgins Trefor , Saw Sharon , Sikaris Ken , Wiley Carmen L , Cembrowski George C. , Lyon Andrew W. , Khajuria Annu , Tran David 
Published: January 2014

Introduction: There are several reports from locations in the northern hemisphere of seasonal variation in hemoglobin A1c (HbA1c) levels with higher values noted in the cooler months. The variation has been attributed to holiday seasons, temperature differences, and changes in diet. This article describes the seasonal variation in both hemispheres and in a country on the equator with minimal temperature variation. Methods: The mean and median HbA1c by month was calculated for a maximum of 2 years for HbA1c data from the different locations: Edmonton and Calgary, Canada; Singapore; Melbourne, Australia; and Marshfield, Wisconsin. The mean monthly temperature for each location was found from available meteorological information. Results: In both northern and southern hemispheres, the HbA1c was higher in cooler months and lower in the warmer months. In Singapore, where there is minimal temperature variation, there is also minimal variation in HbA1c values over the year. The difference in HbA1c over a year appears to be related to the difference in temperature. Conclusion: Hemoglobin A1c is higher in cooler months and lower in the warmer months in both hemispheres. In a country with minimal monthly temperature variation, there is only minimal variation in HbA1c values through the year. In all locations, the mean and median HbA1c declined over the study period, possibly due to better glycemic control of patients with diabetes or an increase in use of HbA1c as a screening test for diabetes or a combination of both.
Improved Glycemic Control through Continuous Glucose Sensor-Augmented Insulin Pump Therapy: Prospective Results from a Community and Academic Practice Patient Registry
Authors: Cohen Ohad , Körner Anna , Chlup Rudolf , Zoupas Christos S. , Ragozin Anton K. , Wudi Krisztina , Bartaskova Dagmar , Pappas Aggelos , Niederland Tamás , Taybani Zoltán , Barák Lubomir , Vazeou Andriani 
Published: January 2014

Background: Conducted by highly experienced investigators with abundant time and resources, phase III studies of continuous glucose sensing (CGS) may lack generalizability to everyday clinical practice. Method: Community or academic practices in six Central and Eastern European or Mediterranean countries prospectively established an anonymized registry of consecutive patients with type 1 insulin-dependent diabetes mellitus starting CGS-augmented insulin pump therapy with the Paradigm® X22 (Medtronic MiniMed, Northridge, CA) under everyday conditions, without prior CGS with another device. We compared glycosylated hemoglobin (GHb) values before and after 3 months of CGS and assessed relationships between insulin therapy variables and glycemia-related variables at weeks 1, 4, and 12 of CGS. Results: Of 102 enrolled patients, 85 (83%) with complete weeks 1, 4, and 12 sensor data and baseline/3-month GHb data were evaluable. Evaluable patients were ∼54% male and ∼75% adult (mean age, 33.2 ± 16.9 years) with longstanding diabetes and high personal/family education levels. Mean GHb declined significantly after 3 months of CGS (7.55 ± 1.33% at baseline to 6.81 ± 1.08% after 12 weeks, 0.74% absolute decrease, P < 0.001). The absolute GHb reduction correlated significantly ( P < 0.0005) with baseline GHb: larger absolute reductions tended to occur when baseline levels were higher. An increased basal insulin dose as a percentage of the total daily insulin dose and a decreased daily bolus count from week 1 to week 12 of CGS predicted GHb improvement from baseline to week 12. Conclusions: CGS-augmented insulin pump therapy appears to improve glycemic control in type 1 diabetes in varied everyday practice settings.
Six-Year Retrospective Follow-Up Study of Safe Screening Intervals for Sight-Threatening Retinopathy in Patients with Diabetes Mellitus
Authors: Soto-Pedre Enrique , Hernaez-Ortega Maria Concepcion , Vázquez José Antonio 
Published: January 2014

Background: We estimate safe screening intervals for sight-threatening diabetic retinopathy (STDR). Methods: A 6-year retrospective follow-up study to review screening results of two cohorts of patients with diabetes mellitus (DM) was conducted; a cohort free of diabetic retinopathy (DR) and a cohort with mild nonproliferative diabetic retinopathy (NPDR) at baseline. Patients had been screened by means of a nonmydriatic retinal camera. Baseline age, sex, and diabetes characteristics were also collected. Statistical analysis was based on life-table method of risk estimation. Results: A total of 286 patients with DM free of DR and 144 patients with mild NPDR at baseline were included in the study. For patients free of DR, the probability of remaining free of STDR was 97% (95% confidence interval [CI] 94–99%) at the end of the fourth year. In this cohort of patients, those with type 2 DM were more likely to progress to STDR than those who had type 1 DM ( p < .01). For patients with mild NPDR, the probability of remaining free of STDR dropped to 94% (95% CI 88–97%) at the end of the second year, and it was still 100% at the end of the second year for those with a glycated hemoglobin level ≤7.5% at baseline ( p < .05). Conclusions: Screening at a 3–4 year interval for diabetes patients free of DR is safe because of their low risk of developing STDR. Patients with mild NPDR require screening at a 1 year interval, or at a 2 year interval with good metabolic control.
A Physiological Model of the Effect of Hypoglycemia on Plasma Potassium
Authors: Christensen Toke Folke , Bækgaard Martin , Dideriksen Jacob Lund , Steimle Kristoffer Lindegaard , Mogensen Mads Lause , Kildegaard Jonas , Struijk Johannes Jan , Hejlesen Ole Kristian 
Published: January 2014

Background: Adrenaline release and excess insulin during hypoglycemia stimulate the uptake of potassium from the bloodstream, causing low plasma potassium (hypokalemia). Hypokalemia has a profound effect on the heart and is associated with an increased risk of malignant cardiac arrhythmias. It is the aim of this study to develop a physiological model of potassium changes during hypoglycemia to better understand the effect of hypoglycemia on plasma potassium. Method: Potassium counterregulation to hypokalemia was modeled as a linear function dependent on the absolute potassium level. An insulin-induced uptake of potassium was modeled using a negative exponential function, and an adrenaline-induced uptake of potassium was modeled as a linear function. Functional expressions for the three components were found using published data. Results: The performance of the model was evaluated by simulating plasma potassium from three published studies. Simulations were done using measured levels of adrenaline and insulin. The mean root mean squared error (RMSE) of simulating plasma potassium from the three studies was 0.09 mmol/liter, and the mean normalized RMSE was 14%. The mean difference between nadirs in simulated and measured potassium was 0.12 mmol/liter. Conclusions: The presented model simulated plasma potassium with good accuracy in a wide range of clinical settings. The limited number of hypoglycemic episodes in the test set necessitates further tests to substantiate the ability of the model to simulate potassium during hypoglycemia. In conclusion, the model is a good first step toward better understanding of changes in plasma potassium during hypoglycemia.
Computing the Risk of Postprandial Hypo- and Hyperglycemia in Type 1 Diabetes Mellitus considering Intrapatient Variability and other Sources of Uncertainty
Authors: García-Jaramillo Maira , Calm Remei , Bondia Jorge , Tarín Cristina , Vehí Josep 
Published: January 2014

Objective: The objective of this article was to develop a methodology to quantify the risk of suffering different grades of hypo- and hyperglycemia episodes in the postprandial state. Methods: Interval predictions of patient postprandial glucose were performed during a 5-hour period after a meal for a set of 3315 scenarios. Uncertainty in the patient's insulin sensitivities and carbohydrate (CHO) contents of the planned meal was considered. A normalized area under the curve of the worst-case predicted glucose excursion for severe and mild hypo- and hyperglycemia glucose ranges was obtained and weighted accordingly to their importance. As a result, a comprehensive risk measure was obtained. A reference model of preprandial glucose values representing the behavior in different ranges was chosen by a X2 test. The relationship between the computed risk index and the probability of occurrence of events was analyzed for these reference models through 19,500 Monte Carlo simulations. Results: The obtained reference models for each preprandial glucose range were 100, 160, and 220 mg/dl. A relationship between the risk index ranges <10, 10–60, 60–120, and >120 and the probability of occurrence of mild and severe postprandial hyper- and hypoglycemia can be derived. Conclusions: When intrapatient variability and uncertainty in the CHO content of the meal are considered, a safer prediction of possible hyper- and hypoglycemia episodes induced by the tested insulin therapy can be calculated.
The Effect of Reduced Somatosensation on Standing Balance: A Systematic Review
Authors: Kars H. J. J. (Cojanne) , Hijmans Juha M. , Geertzen Jan H. B. , Zijlstra Wiebren 
Published: January 2014

The objective of this review is to identify and review publications describing the impact of reduced somatosensation on balance. Based on knowledge of the association between specific somatosensory loss and deterioration of balance, conclusions can be made about role of somatosensation in standing balance. A systematic literature review is presented in which publications from the years 1993 through 2007 were searched in Medline and Embase. Medical Subject Headings (MESH) terms and free text words (related to balance, somatosensory loss, and lower limb) were used to perform the searches. Fifteen articles were selected for detailed review based on predetermined inclusion criteria, and three of the included articles described the effect of experimentally reduced somatosensation on balance in healthy subjects. Ten of the articles described balance in diabetic neuropathy (DN). The last two included articles described balance in Charcot-Marie-Tooth (CMT) disease type 1A (CMT1A) or type 2 (CMT2). The literature indicates that the tactile sensation is reduced in DN, CMT1A, and CMT2 and when the plantar surface of the feet was hypothermically anesthetized. Joint motion sensation seems to be impaired in patients with DN, and passive joint position sensation appears to be reduced in healthy subjects with anesthesia of ankle and foot from prolonged ischemia. This reduced somatosensation seems to have a negative effect on balance in patients with DN and CMT2; however, this appeared not to be the case in patients with CMT1A and in healthy subjects.
Probabilistic Evolving Meal Detection and Estimation of Meal Total Glucose Appearance
Authors: Cameron Fraser , Niemeyer Günter , Buckingham Bruce A. 
Published: January 2014

Background: Automatic compensation of meals for type 1 diabetes patients will require meal detection from continuous glucose monitor (CGM) readings. This is challenged by the uncertainty and variability inherent to the digestion process and glucose dynamics as well as the lag and noise associated with CGM sensors. Thus any estimation of meal start time, size, and shape is fundamentally uncertain. This uncertainty can be reduced, but not eliminated, by estimating total glucose appearance and using new readings as they become available. Method: In this article, we propose a probabilistic, evolving method to detect the presence and estimate the shape and total glucose appearance of a meal. The method is unique in continually evolving its estimates and simultaneously providing uncertainty measures to monitor their convergence. The algorithm operates in three phases. First, it compares the CGM signal to no-meal predictions made by a simple insulin-glucose model. Second, it fits the residuals to potential, assumed meal shapes. Finally, it compares and combines these fits to detect any meals and estimate the meal total glucose appearance, shape, and total glucose appearance uncertainty. Results: We validate the performance of this meal detection and total glucose appearance estimation algorithm both separately and in cooperation with a controller on the Food and Drug Administration-approved University of Virginia/Padova Type I Diabetes Simulator. In cooperation with a controller, the algorithm reduced the mean blood glucose from 137 to 132 mg/dl over 1.5 days of control without any increased hypoglycemia. Conclusion: This novel, extensible meal detection and total glucose appearance estimation method shows the feasibility, relevance, and performance of evolving estimates with explicit uncertainty measures for use in closed-loop control of type 1 diabetes.
New Approaches to Display of Self-Monitoring of Blood Glucose Data
Authors: Rodbard David 
Published: January 2014

Background: There is a need for improved methods for display and analysis of self-monitoring of blood glucose (SMBG) data to facilitate identification of clinical problems, assist the clinician in the interpretation of daily patterns and longitudinal trends, serve as a guide to locating the most important segments of logbook data, and permit rapid analysis of the patient's pattern of glucose monitoring. Methods: We developed prototype software to display SMBG data in a two-dimensional color-coded array: Time of day is displayed on the horizontal axis; date or sequential day is displayed on the vertical axis. Each glucose value is shown by a color-coded symbol categorizing it as “very high,” “high,” “within target range,” “low,” or “very low.” The number of categories and their ranges can be defined by the user, and different target ranges and limits for the categories can be used for different times of day. Placing the cursor over any observation activates a “pop-up box” showing the date, day of week, time of day, glucose value, and ancillary information. Several options and variations are available. Results: This new type of display is compact, serves as a guide to assist the physician in locating the most important segments of the logbook, and permits display of glucose data from 90 or more days in a chart as small as 4 by 4 inches. This analysis permits rapid identification of measurements that are above or below the target range and facilitates rapid evaluation of patterns observed on different days or days of the week. Conclusion: These new approaches complement other popular graphical displays by conveying information efficiently and effectively to the physician, other health care providers, the patient, and family caregivers in a new and novel, concise, standardized yet flexible format.