bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Efficacy of Closed-Loop Glucose Regulation via Control-Variability Grid Analysis
Authors: Magni Lalo , Raimondo Davide M. , Man Chiara Dalla , Breton Marc , Patek Stephen , De Nicolao Giuseppe , Cobelli Claudio , Kovatchev Boris P. 
Published: January 2014

Background: Advancements in subcutaneous continuous glucose monitoring and subcutaneous insulin delivery are stimulating the development of a minimally invasive artificial pancreas that facilitates optimal glycemic regulation in diabetes. The key component of such a system is the blood glucose controller for which different design strategies have been investigated in the literature. In order to evaluate and compare the efficacy of the various algorithms, several performance indices have been proposed. Methods: A new tool—control-variability grid analysis (CVGA)—for measuring the quality of closed-loop glucose control on a group of subjects is introduced. It is a method for visualization of the extreme glucose excursions caused by a control algorithm in a group of subjects, with each subject presented by one data point for any given observation period. A numeric assessment of the overall level of glucose regulation in the population is given by the summary outcome of the CVGA. Results: It has been shown that CVGA has multiple uses: Comparison of different patients over a given time period, of the same patient over different time periods, of different control laws, and of different tuning of the same controller on the same population. Conclusions: Control-variability grid analysis provides a summary of the quality of glycemic regulation for a population of subjects and is complementary to measures such as area under the curve or low/high blood glucose indices, which characterize a single glucose trajectory for a single subject.
Bariatric Surgery and Type 2 Diabetes Mellitus: Surgically Induced Remission
Authors: Tejirian Talar , Jensen Candice , Dutson Erik 
Published: January 2014

The relationship between obesity and type 2 diabetes mellitus (T2DM) is well known. Morbidly obese patients with T2DM who undergo bariatric surgery have improvement or remission of their diabetes. Different types of bariatric operations offer varying degrees of T2DM remission. These operations are classified as restrictive, malabsorptive, or a combination of both. The gold-standard operation, known as the Roux-en-Y gastric bypass, is a combination operation. Most often, improvement of the diabetes is seen within days of the operation. Various theories to explain this rapid change include calorie restriction and hormonal changes from exclusion of the upper gastrointestinal tract. Weight loss accounts for the sustained improvements in glucose control. The patients who benefit the most are those who are early in their disease course. Having a single treatment for both obesity and T2DM is ideal. As bariatric surgery has become a safe operation when performed by experienced surgeons, it should be considered a treatment for these diseases. The impact it can have on the lives of individual patients and society as a whole is tremendous.
Use of Continuous Subcutaneous Insulin Infusion (Insulin Pump) Therapy in the Hospital: A Review of One Institution's Experience
Authors: Leonhardi Brenda J. , Boyle Mary E. , Beer Karen A. , Seifert Karen M. , Bailey Marilyn , Miller-Cage Victoria , Castro Janna C. , Bourgeois Peggy B. , Cook Curtiss B. 
Published: January 2014

Background: This article reviews the performance of our hospital's inpatient insulin pump policy. Methods: Twenty-five hospital admissions of 21 unique patients receiving outpatient insulin pump therapy were reviewed. Results: Between November 1, 2005, and November 30, 2006, there were 25 hospital admissions involving 21 patients receiving outpatient insulin pump therapy. The average age and duration of diabetes among these 21 patients was 50 and 29 years, respectively; 67% were women, 90% had type 1 diabetes, and all were white. The mean length of hospital stay was 4 days, and the average reported length of insulin pump therapy was 4 years. Patients in 16 of the admissions were identified as candidates for continued use of the insulin pump during the hospital stay. Over 90% of patients remaining on the insulin pump had documentation by nursing of the presence of the pump at the time of admission; 100% of the patients had an admission glucose recorded; 88% had a record of signed patient consent; 81% had evidence of completed preprinted insulin pump orders; 75% received a required endocrine consultation; and 75% of cases had documentation of completed bedside flow sheet. A high frequency of both hypoglycemic and hyperglycemic events occurred in the patients; however, no adverse events were related directly to the insulin pump. Conclusions: Insulin pump therapy can be safely continued in the hospital setting. While staff compliance with required procedures was high, there was still room for improvement. More data are needed, however, on whether this method of insulin delivery is effective for controlling hyperglycemia in hospitalized patients.
Further Development of Artificial Pancreas: Blocked by Patents?
Authors: Erdin Nils , Robin Franck , Heinemann Lutz , Brandt Derek , Hovorka Roman 
Published: January 2014

Patent activity in the field of medical device technology and especially in the area of artificial pancreas development has surged in recent years. According to the search presented in this article, the number of granted U.S. patents in the area of closed-loop glucose control (CLGC) increased from 24 filed in 1991 to 247 filed in 2001. A company active in the area of diabetes technology development will likely need to understand a patent landscape consisting of hundreds of patents. Currently, both in the United States and in Europe, patentability requirements seem to be raised in order to ensure patent quality. However, the current patent landscape reflects the work of the patent offices in the past, as already granted patents are not affected by changes made to the patent grant procedure today. Regarding the increasing amount of patents and considering the complexity of CLGC systems, the attempt to develop a CLGC system will become more and more venturesome regarding the risk of infringement of already existing patents. The consequence of this situation can be that less innovation takes place. This article highlights some important general aspects of the patent system, briefly characterizes the current CLGC patent landscape, and illustrates by means of two exemplary patents what one angle of said patent landscape looks like. It is our opinion that, in order to support the rapid development of an artificial pancreas for patients with diabetes, adequate action to lower this hurdle should be undertaken by a consortium of all parties involved (industries, patient organizations, health-care professionals, and institutional payers).
Development of Novel Glucose Sensing Fluids with Potential Application to Microelectromechanical Systems-Based Continuous Glucose Monitoring
Authors: Li Siqi , Huang Xian , Davis Erin N. , Lin Qiao , Wang Qian 
Published: January 2014

Background: We have previously presented a microelectromechanical systems (MEMS) viscometric sensor for continuous glucose monitoring. The sensing fluid used therein was based on protein concanavalin A, which is known to have significant drawbacks, such as immunotoxicity and instability. To address this issue, a stable, biocompatible polymeric sensing fluid has been developed. Methods: In the polymeric sensing system, glucose reversibly formed strong ester bonds with the phenylboronic acid moiety on the poly(acrylamide- ran-3-acrylamidophenylboronic acid) (PAA- ran-PAAPBA) polymer backbone, resulting in cross-linking of the copolymers and an increase in the solution viscosity. The copolymers were synthesized via classic free radical copolymerization processes. The viscosity of the PAA- ran-PAAPBA, dissolved in phosphate-buffered saline buffer and in the presence of glucose at physiologically relevant concentrations, was measured by an Ubbelodhe viscometer and a prototype MEMS viscometric device. Results: Experimental results showed that the polymer molecular weight and composition depended on the solvent quantity, while the sensing fluid viscosity was determined by the polymer molecular weight and percentage composition of PAAPBA. The study of the temperature effect on viscosity showed that the polymer sensed glucose effectively under physiological conditions, although the high temperature lowered its sensitivity. Through proper adjustment of these parameters, a distinctive viscosity increase was observed when the glucose concentration increased from 0 to 450 mg/dl, which was detectable by our prototype MEMS device. Conclusions: We have successfully developed a stable, biocompatible polymeric system for the sensitive detection of glucose. MEMS experiments demonstrated that the sensing fluid was able to sense glucose at different concentrations. This sensing system can potentially enable highly reliable, continuous monitoring of glucose in interstitial fluid from subcutaneous tissue.
German-Translated Norfolk Quality of Life (QOL-DN) Identifies the Same Factors as the English Version of the Tool and Discriminates Different Levels of Neuropathy Severity
Authors: Vinik Etta J. , Paulson James F. , Ford-Molvik Stephanie L. , Vinik Aaron I. 
Published: January 2014

Background: The development and validation of Norfolk QOL-DN, a fiber-specific, quality-of-life tool for diabetic neuropathy, was published previously (Part 1). This study (Part 2) defines the psychometric properties of the German-translated Norfolk QOL-DN in a large multicenter (96 sites) population with neuropathy ranging from minimal to severe, comparing them with those in the origina51 English/American version in a 30-center European/North American population with mild neuropathy; determines the power of the German-translated version in a five-staged diabetic peripheral neuropathy (DPN) German population to discriminate different levels of neuropathy severity; and establishes factors having the greatest impact on QOL. Methods: One hundred eighty-six German patients were assessed: asymptomatic of DPN ( n = 40), symptomatic ( n = 46), DN with foot-ulcer history ( n = 32), DN with amputations ( n = 22), and DN amputation history ( n = 46). German-translated Norfolk QOL-DN was administered to 177 patients with staged DN complications. German-translated Norfolk QOL-DN data were compared with QOL-DN data from the European/American study of 379 mild neuropathy patients. Exploratory factor analysis assessed factor structure consistency in the translated instrument. Ordinal regression analysis (polytomous universal model) was used to evaluate the association between factor scores and complication stages. Results: The German translation identified the same five factors in more advanced neuropathy as in the English mild neuropathy population. Total QOL scores differed among each of the five neuropathy severity groups [analysis of variance p < 0.001, Tukey-Kramer post hoc, α = 0.05]. Two factors emerged as predictors of impaired QOL and disease severity: physical function/large fiber (Wald X2 = 6.188, p = 0.013) and activities of daily living (ADL)(Wald X2 = 9.098, p = 0.003). Conclusions: Norfolk QOL-DN discriminates levels of neuropathy within and between populations. Physical functioning and ADL are the most important determinants of QOL. Early occurrence of orthostasis suggests a redefinition of autonomic neuropathy to be more symptom inclusive.
Intensive Care Unit Insulin Delivery Algorithms: Why So Many? How to Choose?
Authors: Steil Garry M. , Deiss Dorothee , Shih Judy , Buckingham Bruce , Weinzimer Stuart , Agus Michael S.D. 
Published: January 2014

Objective: Studies showing improved outcomes with tight glycemic control in the intensive care unit (ICU) have resulted in a substantial number of new insulin delivery algorithms being proposed. The present study highlights mechanisms used in the better-known approaches, examines what might be critical differences among them, and uses systems theory to characterize the conditions under which each can be expected to perform best. Methods: Algorithm dose (ΔI/ΔG) and step (response to a persistent elevation in glucose) response curves were calculated for written instruction algorithms, developed at the Providence Heart and Vascular Institute (Portland [P] protocol), the University of Washington (UW), and Yale University (Y), together with similar curves for the Glucommander (GM) and proportional integral derivative (PID) computer algorithms. From the simulated curves, different mechanisms used to adjust insulin delivery were identified. Results: All algorithms increased insulin delivery in response to persistent hyperglycemia, but the mechanism used altered the algorithm's sensitivity to glucose, or gain, in the GM, UW, and Y protocols, while leaving it unchanged for the P protocol and PID algorithm. Conclusions: The increase in insulin delivery in response to persistent hyperglycemia observed with all the algorithms can be expected to bring subjects who respond to insulin to targeted glucose ranges. However, because the PID and P protocols did not alter the insulin delivery response curves, these algorithms can be expected to take longer to achieve target glucose levels in individuals who are insulin resistant and/or are exposed to increased carbohydrate loads (e.g., glucose infusions). By contrast, the GM, UW, and Y algorithms can be expected to adapt to the insulin resistance such that the time to achieve target levels is unchanged if the time for insulin to act does not change. If the insulin resistance is accompanied by a longer time for insulin to act, the UW, Y, and GM algorithms may increase the risk of hypoglycemia. Under these conditions, the longer time required for the PID and P protocols to achieve a target glucose level may be a reasonable trade-off for no increase in the risk of hypoglycemia.
A Liquid Chromatography/Tandem Mass Spectrometry Method for Determination of 25-Hydroxy Vitamin D2 and 25-Hydroxy Vitamin D3 in Dried Blood Spots: A Potential Adjunct to Diabetes and Cardiometabolic Risk Screening
Authors: Newman Mark S. , Brandon Theodore R. , Groves Margaret N. , Gregory William L. , Kapur Sanjay , Zava David T. 
Published: January 2014

Background: Now emerging as an important risk factor for type 1 diabetes, vitamin D deficiency is also associated with obesity, metabolic syndrome, and type 2 diabetes and has been identified as a potential cardiometabolic risk factor. A simple, accurate screening test for 25-hydroxy vitamin D [25(OH)D] deficiency is needed. We developed a liquid chromatography/tandem mass spectrometry assay for 25-hydroxy vitamin D2 [25(OH)D2] and 25-hydroxy vitamin D3 [25(OH)D3] in dried blood spots. Method: Blood spots were collected by finger stick simultaneously with serum samples obtained by venipuncture from healthy volunteers. Disks punched from the dried blood spots were sonicated with an internal standard solution of deuterated 25(OH)D3 (26,26,26,27,27,27-d6). Methanol was added to precipitate proteins prior to extraction with hexane. The extracted samples were dried and reconstituted in 50:50 methanol:H2O before injection into a Varian 320-MS TQ mass spectrometer. Results: Blood spot assay precision was good over the reportable range: interassay coefficients of variation were 13, 13, and 11% at concentrations of 14, 26, and 81 ng/ml, respectively, for 25-hydroxy vitamin D3 and 12% at 23 ng/ml for 25(OH)D2. The 25(OH)D3 assay was linear from 3.5 to 75 ng/ml (R > 0.99). Blood spot and serum values showed excellent correlation for 25(OH)D2 ( R = 0.90, n = 54) and 25(OH)D3 ( R = 0.91, n = 83). Conclusions: This blood spot assay for 25(OH)D2 and 25(OH)D3 provides a convenient and cost-effective alternative to serum assays and can be automated. This may be valuable in large-scale screening for risk of type 1 diabetes, for cardiometabolic risk screening, and for monitoring vitamin D supplementation.
The Potential Use of Radio Frequency Identification Devices for Active Monitoring of Blood Glucose Levels
Authors: Moore Bert 
Published: January 2014

Imagine a diabetes patient receiving a text message on his mobile phone warning him that his blood glucose level is too low or a patient's mobile phone calling an emergency number when the patient goes into diabetic shock. Both scenarios depend on automatic, continuous monitoring of blood glucose levels and transmission of that information to a phone. The development of advanced biological sensors and integration with passive radio frequency identification technologies are the key to this. These hold the promise of being able to free patients from finger stick sampling or externally worn devices while providing continuous blood glucose monitoring that allows patients to manage their health more actively. To achieve this promise, however, a number of technical issues need to be addressed.
Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations
Authors: Lehmann Eldon D. , Tarín Cristina , Bondia Jorge , Teufel Edgar , Deutsch Tibor 
Published: January 2014

Introduction: AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. Methods: This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. Discussion: The methodology to be adopted for implementing the generic absorption model within AIDA has been overviewed, and the first plasma insulin profiles based on this approach have been demonstrated. Ideas for future work and development are discussed. It is expected that an updated release of AIDA (v4.5), based on this collaborative approach, will become available for free—in due course—via the www.2aida.org Web site. Readers who wish to be informed when the new software is launched can join the very low volume AIDA announcement list by sending a blank email note to subscribe@2aida.org . Results: Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as well as for insulin doses up to 50 IU.
Improving Access to Eye Care: Teleophthalmology in Alberta, Canada
Authors: Ng ManCho , Nathoo Nawaaz , Rudnisky Chris J. , Tennant Matthew T. S. 
Published: January 2014

Background: Diabetic retinopathy in Alberta and throughout Canada is common, with a prevalence up to 40% in people with diabetes. Unfortunately, due to travel distance, time, and expense, a third of patients with diabetes do not receive annual dilated eye examinations by ophthalmologists, despite universal health care access. In an effort to improve access, a teleophthalmology program was developed to overcome barriers to eye care. Prior to clinical implementation, teleophthalmology technology was clinically validated for the identification of treatable levels of diabetic retinopathy. Method: Patients undergoing a teleophthalmology assessment underwent stereoscopic digital retinal photographs following pupillary dilation. Digital images were then packaged into an encrypted password-protected compressed file for uploading onto a secure server. Images were digitally unpackaged for review as a stereoscopic digital slide show and graded with a modified Early Treatment Diabetic Retinopathy Study algorithm. Reports were then generated automatically as a PDF file and sent back to the referring physician. Results: Teleophthalmology programs in Alberta have assessed more than 5500 patients (9016 visits) to date. Nine hundred thirty patients have been referred for additional testing or treatment. Approximately 2% of teleophthalmology assessments have required referral for in-person examination due to ungradable image sets, most commonly due to cataract, corneal drying, or asteroid hyalosis. Conclusions: In Alberta and throughout Canada, many patients with diabetes do not receive an annual dilated eye examination. Teleophthalmology is beneficial because patients can be assessed within their own communities. This decreases the time to treatment, allows treated patients to be followed remotely, and prevents unnecessary referrals. Health care costs may be reduced by the introduction of comprehensive teleophthalmology examinations by enabling testing and treatment to be planned prior to the patient's first visit.
Variation in the Frequency of Hemoglobin A1c (HbA1c) Testing: Population Studies Used to Assess Compliance with Clinical Practice Guidelines and Use of HbA1c to Screen for Diabetes
Authors: Lyon Andrew W. , Higgins Trefor , Wesenberg James C. , Tran David V. , Cembrowski George S. 
Published: January 2014

Background: The volume of hemoglobin A1c (HbA1c) testing has increased dramatically over the past decade and few studies have attempted to determine how the test is used. The goals of this study were to evaluate the frequency of HbA1c testing in regional populations to assess the extent of screening for diabetes and to determine if the HbA1c testing intervals of known diabetic patients were consistent with clinical practice guidelines. Methods: Two years of HbA1c results were extracted from laboratory information systems in four regions of the province of Alberta that represent urban, mixed urban-rural, and rural populations. HbA1c testing frequencies and the proportions of nondiabetic patients undergoing HbA1c tests were derived. Results: Approximately 60% of HbA1c tests in each region were done on patients who had only a single test during the 2-year interval. Testing of nondiabetic patients accounted for 24% of HbA1c tests and varied by region. While the cumulative frequency distributions of HbA1c test intervals resembled each other, detailed analyses of the frequency distributions depicted broad multimodal peaks and regional variations that suggest a great deal of heterogeneity among practices. The most common HbA1c testing interval was 3 months ± 3 weeks in each region and is consistent with the 3-month test interval target in a clinical practice guideline. Conclusions: HbA1c testing is being performed on a substantial proportion of nondiabetic patients. On average, patients with diabetes in Alberta receive 1.5 HbA1c tests per year. However, we observed regional differences in the frequency of testing and variation in compliance with clinical practice guidelines.