bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Correlation of Hemoglobin A1c to Blood Glucose
Authors: Sikaris Ken 
Published: January 2014

The understanding that hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes. Even in making such a statement, we speak of “average blood glucose” as though “blood glucose” were itself a simple idea. When we consider all the blood glucose forms—arterial versus venous versus capillary, whole blood versus serum versus fluoride-preserved plasma, fasting versus nonfasting—we can start to see that this is not a simple issue. Nevertheless, it seems as though HbA1c correlates to any single glucose measurement. Having more than one measurement and taking those measurements in the preceding month improves the correlation further. In particular, by having glucose measurements that reflect both the relatively lower overnight glucose levels and measurements that reflect the postprandial peaks improves not only our ability to manage diabetes patients, but also our understanding of how HbA1c levels are determined. Modern continuous glucose monitoring (CGM) devices may take thousands of glucose results over a week. Several studies have shown that CGM glucose averages account for the vast proportion of the variation of HbA1c. The ability to relate HbA1c to average glucose may become a popular method for reporting HbA1c, eliminating current concerns regarding differences in HbA1c standardization. Hemoglobin A1c expressed as an average glucose may be more understandable to patients and improve not only their understanding, but also their ability to improve their diabetes management.
Noninvasive Ultrasonic Glucose Sensing with Large Pigs (∼200 Pounds) Using a Lightweight Cymbal Transducer Array and Biosensors
Authors: Park Eun-Joo , Werner Jacob , Beebe Joshua , Chan Samantha , Smith Nadine Barrie 
Published: January 2014

Background: To prevent complications in diabetes, the proper management of blood glucose levels is essential. Since conventional glucose meters require pricking fingers or other areas of the skin, a noninvasive method for monitoring blood glucose levels is desired. Using a lightweight cymbal transducer array, this study was conducted to noninvasively determine the glucose levels of pigs having a similar size to humans. Method: In vivo experiments using eight pigs (∼200 pounds) were performed in five groups. A cymbal array with four biosensors was attached to the axillary area of the pig. The array was operated at 20 kHz at special peak-temporal peak intensity (Isptp) equal to 50 or 100 mW/cm2 for 5, 10, or 20 minutes. After the ultrasound exposure, glucose concentrations of the interstitial fluid were determined using biosensors. For comparison, glucose levels of blood samples collected from the ear vein were measured by a commercial glucose meter. Result: In comparison, glucose levels determined by a cymbal array and biosensor system were close to those measured by a glucose meter. After a 20-minute ultrasound exposure at Isptp = 100 mW/cm2, the average glucose level determined by the ultrasound system was 175 ± 7 mg/dl, which is close to 166 ± 5 mg/dl measured by the glucose meter. Conclusion: Results indicate the feasibility of using a cymbal array for noninvasive glucose sensing on pigs having a similar size to humans. Further studies on the ultrasound conditions, such as frequency, intensity, and exposure time, will be continued for effective glucose sensing.
Closing the Circle of Care with New Firmware for Diabetes: MyDiaBase+RxChecker
Authors: Albisser A. Michael , Alejandro Rodolfo , Sperlich Marianne , Ricordi Camillo 
Published: January 2014

Background: Satisfactory glycemic control, meeting American Diabetes Association recommendations, is difficult to achieve. Technologically, this is most likely because the circle of care is incomplete. Many have suggested that the introduction of information technology may remedy the situation. However, previous attempts have not succeeded. Recognizing this, we evolved firmware that supports and links both the patient at home and their care providers in the clinic. Firmware Design and Methods: The device includes software and a database, all contained in a standard USB flash drive. At home, patients use the database portion of the device (MyDiaBase). It fully complements their diabetes education while capturing pertinent self-management information by tracking self-monitored blood glucose data, body weight, medication dosing, physical activity, diet, lifestyle, and stress. In the clinic, providers use the RxChecker program to perform prescription checks that are based on their patients' outcomes data, thereby effectively closing the circle of care.
Usefulness of Point-of-Care Testing in the Treatment of Diabetes in an Underserved Population
Authors: Leal Sandra , Soto-Rowen Marisa 
Published: January 2014

Background: The purpose of this article was to communicate our experience with point-of-care testing (POCT) using Bayer's A1CNow+® device to test glycated hemoglobin (A1C) in the management of diabetes and to share the observations of our quality control efforts. Methods: Forty-seven patients' POCT samples were compared with laboratory samples to determine the validity of the POCT sample being drawn. Data collected represent a 10-month time period that were drawn on-site with the following distribution: 36 samples were drawn the same day, 7 samples were drawn 1 day later, 3 samples were drawn within 3 days, and 1 sample was drawn 4 days later. Although all samples were collected on-site, some of the samples were sent to other local branches of nationally recognized laboratories for analysis. Results: The range of A1C results for the POCT group was 5.6 to >13%. The range of A1C results for the laboratory-drawn group was 5 to 12.6%. Twenty-four patients had laboratory results that read lower than the result obtained in the clinic, with an A1C range of 5 to 12.6%, and two patients had laboratory results that read exactly the same as the result obtained in the clinic when using POCT. These two individuals had A1C results of 9.1 and 12.6%. Analysis of data collected determined an r value of 0.918 demonstrating agreement between the POCT samples and the laboratory samples. Conclusions: POCT with the A1CNow+ is an effective, economical tool for use in a pharmacist-based diabetes clinic that serves a high-risk underserved population. POCT allows the pharmacist the ability to use on-site results to inform patients of their progress, modify their therapy immediately with an immediate face-to-face opportunity to assure understanding, and provide a self-management goal.
Gastric Electrical Stimulation with the TANTALUS® System in Obese Type 2 Diabetes Patients: Effect on Weight and Glycemic Control
Authors: Sanmiguel Claudia P. , Conklin Jeffrey L. , Cunneen Scott A. , Barnett Philip , Phillips Edward H. , Kipnes Mark , Pilcher John , Soffer Edy E. 
Published: January 2014

Background: The TANTALUS® System is an investigational device that consists of an implantable pulse generator connected to gastric electrodes. The system is designed to automatically detect when eating starts and only then deliver sessions of gastric electrical stimulation (GES) with electrical pulses that are synchronized to the intrinsic antral slow waves. We report the effect of this type of GES on weight loss and glucose control in overweight/obese subjects with type 2 diabetes mellitus (T2DM). This study was conducted under a Food and Drug Administration/Institutional Review Board-approved investigational device exemption. Method: Fourteen obese T2DM subjects on oral antidiabetes medication were enrolled and implanted laparoscopically with the TANTALUS System (body mass index 39 ± 1 kg/m2, hemoglobin A1c [HbA1c] 8.5 ± 0.2%). Gastric electrical stimulation was initiated four weeks after implantation. Weight, HbA1c, fasting blood glucose, blood pressure, and lipid levels were assessed during the study period. Results: Eleven subjects reached the 6-month treatment period endpoint. Gastric electrical stimulation was well tolerated by all subjects. In those patients completing 6 months of therapy, HbA1c was reduced significantly from 8.5 ± 0.7% to 7.6 ± 1%, p < .01. Weight was also significantly reduced from 107.7 ± 21.1 to 102.4 ± 20.5 kg, p < .01. The improvement in glucose control did not correlate with weight loss ( R2 = 0.05, p = .44). A significant improvement was noted in blood pressure, triglycerides, and cholesterol (low-density lipoprotein only). Conclusions: Short-term therapy with the TANTALUS System improves glucose control, induces weight loss, and improves blood pressure and lipids in obese T2DM subjects on oral antidiabetes therapy.
Closed-Loop Artificial Pancreas Using Subcutaneous Glucose Sensing and Insulin Delivery and a Model Predictive Control Algorithm: The Virginia Experience
Authors: Clarke William L. , Anderson Stacey , Breton Marc , Patek Stephen , Kashmer Laurissa , Kovatchev Boris 
Published: January 2014

Background: Recent progress in the development of clinically accurate continuous glucose monitors (CGMs), automated continuous insulin infusion pumps, and control algorithms for calculating insulin doses from CGM data have enabled the development of prototypes of subcutaneous closed-loop systems for controlling blood glucose (BG) levels in type 1 diabetes. The use of a new personalized model predictive control (MPC) algorithm to determine insulin doses to achieve and maintain BG levels between 70 and 140 mg/dl overnight and to control postprandial BG levels is presented. Methods: Eight adults with type 1 diabetes were studied twice, once using their personal open-loop systems to control BG overnight and for 4 h following a standardized meal and once using a closed-loop system that utilizes the MPC algorithm to control BG overnight and for 4 h following a standardized meal. Average BG levels, percentage of time within BG target of 70–140 mg/dl, number of hypoglycemia episodes, and postprandial BG excursions during both study periods were compared. Results: With closed-loop control, once BG levels achieved the target range (70–140 mg/dl), they remained within that range throughout the night in seven of the eight subjects. One subject developed a BG level of 65 mg/dl, which was signaled by the CGM trend analysis, and the MPC algorithm directed the discontinuance of the insulin infusion. The number of overnight hypoglycemic events was significantly reduced ( p = .011) with closed-loop control. Postprandial BG excursions were similar during closed-loop and open-loop control Conclusion: Model predictive closed-loop control of BG levels can be achieved overnight and following a standardized breakfast meal. This “artificial pancreas” controls BG levels as effectively as patient-directed open-loop control following a morning meal but is significantly superior to open-loop control in preventing overnight hypoglycemia.
Control to Range for Diabetes: Functionality and Modular Architecture
Authors: Kovatchev Boris , Patek Stephen , Dassau Eyal , Doyle Francis J. , Magni Lalo , De Nicolao Giuseppe , Cobelli Claudio ,   Juvenile Diabetes Research Foundation Artificial Pancreas Consortium
Published: January 2014

Background: Closed-loop control of type 1 diabetes is receiving increasing attention due to advancement in glucose sensor and insulin pump technology. Here the function and structure of a class of control algorithms designed to exert control to range, defined as insulin treatment optimizing glycemia within a predefined target range by preventing extreme glucose fluctuations, are studied. Methods: The main contribution of the article is definition of a modular architecture for control to range. Emphasis is on system specifications rather than algorithmic realization. The key system architecture elements are two interacting modules: range correction module, which assesses the risk for incipient hyper- or hypoglycemia and adjusts insulin rate accordingly, and safety supervision module, which assesses the risk for hypoglycemia and attenuates or discontinues insulin delivery when necessary. The novel engineering concept of range correction module is that algorithm action is relative to a nominal open-loop strategy—a predefined combination of basal rate and boluses believed to be optimal under nominal conditions. Results: A proof of concept of the feasibility of our control-to-range strategy is illustrated by using a prototypal implementation tested in silico on patient use cases. These functional and architectural distinctions provide several advantages, including (i) significant insulin delivery corrections are only made if relevant risks are detected; (ii) drawbacks of integral action are avoided, e.g., undershoots with consequent hypoglycemic risks; (iii) a simple linear model is sufficient and complex algorithmic constraints are replaced by safety supervision; and (iv) the nominal profile provides straightforward individualization for each patient. Conclusions: We believe that the modular control-to-range system is the best approach to incremental development, regulatory approval, industrial deployment, and clinical acceptance of closed-loop control for diabetes.
A Novel Adaptive Basal Therapy Based on the Value and Rate of Change of Blood Glucose
Authors: Wang Youqing , Percival Matthew W. , Dassau Eyal , Zisser Howard C. , Jovanovič Lois , Doyle Francis J. 
Published: January 2014

Background: Modern insulin pump therapy for type 1 diabetes mellitus offers the freedom to program several basal profiles that may accommodate diurnal variability in insulin sensitivity and activity level. However, these basal profiles do not change even if a pending hypoglycemic or hyperglycemic event is foreseen. New insulin pumps could receive a direct feed of glucose values from a continuous glucose monitoring (CGM) system and could enable dynamic basal adaptation to improve glycemic control. Method: The proposed method is a two-step procedure. After the design of an initial basal profile, an adaptation of the basal rate is suggested as a gain multiplier based on the current CGM glucose value and its rate of change (ROC). Taking the glucose value and its ROC as axes, a two-dimensional plane is divided into a nine-zone mosaic, where each zone is given a predefined basal multiplier; for example, a basal multiplier of zero indicates a recommendation to shut off the pump. Results: The proposed therapy was evaluated on 20 in silico subjects (ten adults and ten adolescents) in the Food and Drug Administration-approved UVa/Padova simulator. Compared with conventional basal therapy, the proposed basal adjustment improved the percentage of glucose levels that stayed in the range of 60–180 mg/dl for all 20 subjects. In addition, the adaptive basal therapy reduced the average blood glucose index values. Conclusions: The proposed therapy provides the flexibility to account for insulin sensitivity variations that may result from stress and/or physical activities. Because of its simplicity, the proposed method could be embedded in a chip in a future artificial pancreatic β cell or used in a “smart” insulin pump.
Serum Insulin Aspart Concentrations following High-Dose Insulin Aspart Administered Directly into the Duodenum of Healthy Subjects: An Open-Labeled, Single-Blinded, and Uncontrolled Exploratory Trial
Authors: Ihlo Charlotte A. , Aksglæde Karin Bak , Laursen Torben , Lauritzen Torsten , Christiansen Jens Sandahl 
Published: January 2014

Objective: The goal of this study was to determine the bioavailability of high-dose insulin aspart administered directly into the duodenum of healthy subjects. Methods: In a pilot study, four subjects each received four escalating doses of a 1-ml solution of insulin aspart (100, 300, 600, and 1000 IU, respectively) directly into the duodenum. In the following main study, eight subjects each received two identical doses of insulin aspart of 1000 IU, in 4- and 8-ml solutions, respectively, directly into the duodenum. Subjects in the main study also received an intravenous and a subcutaneous injection of 4 to 6 IU of insulin aspart. Results: A considerable number of samples and, in some cases, consecutive samples revealed significantly increased concentrations of serum insulin aspart. Despite the significant serum insulin aspart concentrations, no significant changes of plasma glucose were measured. Moreover, no significant suppression of endogenous insulin secretion was detected, as assessed by the levels of serum human insulin. Conclusions: Administration of high-dose insulin aspart directly into the duodenum of healthy subjects resulted in significantly increased serum insulin aspart concentrations in a high number of consecutive samples using a specific enzyme-linked immunosorbent assay. However, no significant changes in the levels of plasma glucose or serum human insulin were observed. Thus, the study did not provide any evidence of biological activity of the original insulin aspart molecule after high-dose administration directly into the duodenum.
A Semilogarithmic Scale for Glucose Provides a Balanced View of Hyperglycemia and Hypoglycemia
Authors: Rodbard David 
Published: January 2014

Objective: It would be desirable to improve the ability of physicians and patients to identify hypoglycemic episodes when viewing displays of glucose by date, time of day, or day of the week. Research Design and Methods: A logarithmic scale is utilized for display of glucose versus date and time of day using a range of 40 to 400 mg/dl. Several plausible alternatives are considered for transformation of the glucose data. Result: Use of a semilogarithmic plot triples the percentage of the vertical axis allocated to hypoglycemia (e.g., 40–80 mg/dl) from 10% to 30.1% while compressing the hyperglycemic region. The log scale improves the symmetry of the glucose distribution. Transformations were evaluated corresponding to the Schlichtkrull M100 value, the high blood glucose index/low blood glucose index of Kovatchev and associates, an index of glycemic control developed by the present author, and the GRADE score of Hill and coworkers. Results are similar for all four transformations. This approach is applicable both to self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM). Based on preliminary results, it is proposed that the log transform could potentially facilitate analysis of glucose patterns and may facilitate rapid and consistent detection and appreciation of the severity and consistency of hypoglycemic episodes, even in the presence of complex overlapping patterns commonly observed in both SMBG and CGM glucose profiles. Conclusion: Display of glucose on a logarithmic scale can potentially improve the accuracy of analysis and interpretation of popular methods for graphic display of glucose values. Device manufacturers should consider including options for semilogarithmic display of glucose on SMBG meters, CGM sensors, and software for retrospective analyses of glucose data.
Plasma-Generating Glucose Monitor Accuracy Demonstrated in an Animal Model
Authors: Magarian Peggy , Sterling Bernhard 
Published: January 2014

Introduction: Four randomized controlled trials have compared mortality and morbidity of tight glycemic control versus conventional glucose for intensive care unit (ICU) patients. Two trials showed a positive outcome. However, one single-center trial and a large multicenter trial had negative results. The positive trials used accurate portable lab analyzers. The negative trial allowed the use of meters. The portable analyzer measures in filtered plasma, minimizing the interference effects. OptiScan Biomedical Corporation is developing a continuous glucose monitor using centrifuged plasma and mid-infrared spectroscopy for use in ICU medicine. The OptiScanner draws approximately 0.1 ml of blood every 15 min and creates a centrifuged plasma sample. Internal quality control minimizes sample preparation error. Interference adjustment using this technique has been presented at the Society of Critical Care Medicine in separate studies since 2006. Method: A good laboratory practice study was conducted on three Yorkshire pigs using a central venous catheter over 6 h while performing a glucose challenge. Matching Yellow Springs Instrument glucose readings were obtained. Results: Some 95.7% of the predicted values were in the Clarke Error Grid A zone and 4.3% in the B zone. Of those in the B zone, all were within 3.3% of the A zone boundaries. The coefficient of determination ( R2) was 0.993. The coefficient of variance was 5.02%. Animal necropsy and blood panels demonstrated safety. Conclusion: The OptiScanner investigational device performed safely and accurately in an animal model. Human studies using the device will begin soon.
Health Technologies for Monitoring and Managing Diabetes: A Systematic Review
Authors: Russell-Minda Elizabeth , Jutai Jeffrey , Speechley Mark , Bradley Kaitlin , Chudyk Anna , Petrella Robert 
Published: January 2014

Background: The primary objective of this review was to determine the strength of evidence for the effectiveness of self-monitoring devices and technologies for individuals with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) based on specific health-related outcome measures. Self-monitoring devices included those that assist patients with managing diabetes and preventing cardiovascular complications (CVCs). A secondary objective was to explore issues of feasibility, usability, and compliance among patients and providers. Methods: Study criteria included individuals ≥14 years and youth (7–14 years) with T1DM or T2DM, intervention with a self-monitoring device, assessment of clinical outcomes with the device, literature in English, and ≥10 participants. Relevant published literature was searched from 1985 to 2008. Randomized controlled trials and observational studies were included. Data were extracted for clinical outcomes, feasibility and compliance methods, and results. Selected studies were independently evaluated with a validated instrument for assessing methodological quality. Results: Eighteen trials were selected. Predominant types of device interventions included self-monitoring of blood glucose, pedometers, and cell phone or wireless technologies. Feasibility and compliance were measured in the majority of studies. Conclusions: Self-monitoring of blood glucose continues to be an effective tool for the management of diabetes. Wireless technologies can improve diabetes self-care, and pedometers are effective lifestyle modification tools. The results of this review indicate a need for additional controlled trial research on existing and novel technologies for diabetes self-monitoring, on health outcomes associated with diabetes and CVCs, and device feasibility and compliance.