bluuebunny/crossref_metadata_2025_split huggingface dataset:
Closed-Loop Insulin Delivery Utilizing Pole Placement to Compensate for Delays in Subcutaneous Insulin Delivery
Authors: Loutseiko Mikhail , Voskanyan Gayane , Keenan D. Barry , Steil Garry M. 
Published: January 2014

Background: We have previously used insulin feedback (IFB) as a component of a closed-loop algorithm emulating the β cell. This was based on the observation that insulin secretion is inhibited by insulin concentration. We show here that the effect of IFB is to make a closed-loop system behave as if delays in the insulin pharmacokinetic (PK)/ pharmacodynamic (PD) response are reduced. We examine whether the mechanism can be used to compensate for delays in the subcutaneous PK/PD insulin response. Method: Closed-loop insulin delivery was performed in seven diabetic dogs using a proportional-integral-derivative model of the β cell modified by model-predicted IFB. The level of IFB was set using pole placement. Meal responses were obtained on three occasions: Without IFB (NONE), reference IFB (REF), and 2xREF, with experiments performed in random order. The ability of the insulin model to predict insulin concentration was evaluated by correlation with the measured profile and results reported as R2. The ability of IFB to improve the meal response was evaluated by comparing peak and nadir postprandial glucose and area under the curve (AUC; repeated measures analysis of variance with post hoc test for linear trend). Results: Insulin concentration was well predicted by the model (median R2 = 0.87, 0.79, and 0.90 for NONE, REF, and 2xREF, respectively). Peak postprandial glucose (294 ± 15, 243 ± 21, and 247 ± 16 mg/dl) and AUC (518.2 ± 36.13, 353.5 ± 45.04, and 280.3 ± 39.37 mg/dl±min) decreased with increasing IFB ( p < .05, linear trend). Nadir glucose was not affected by IFB (76 ± 5.4, 68 ± 7.3, and 72 ± 4.3 mg/dl; p = .63). Conclusions: Insulin feedback provides an effective mechanism to compensate for delay in the insulin PK/PD profile.
Meta-Analysis of Overnight Closed-Loop Randomized Studies in Children and Adults with Type 1 Diabetes: The Cambridge Cohort
Authors: Kumareswaran Kavita , Elleri Daniela , Allen Janet M. , Harris Julie , Xing Dongyuan , Kollman Craig , Nodale Marianna , Murphy Helen R. , Amiel Stephanie A. , Heller Simon R. , Wilinska Malgorzata E. , Acerini Carlo L. , Evans Mark L. , Dunger David B. , Hovorka Roman 
Published: January 2014

Aim: We reviewed the safety and efficacy of overnight closed-loop insulin delivery compared with conventional continuous subcutaneous insulin infusion (CSII) in two distinct age groups with type 1 diabetes mellitus (T1DM), young people aged 5 to 18 years and adults, combining data of previously published randomized studies. Methods: We evaluated four randomized crossover studies in 17 children and adolescents [13.4 ± 3.6 years; mean ± standard deviation (SD)] and 24 adults (37.5 ± 9.1 years) on 45 closed-loop (intervention) and 45 CSII (control) visits. Each subject attended for two overnight study visits, using either closed-loop or conventional pump therapy, in random order. In each age group, studies were designed to mimic realistic likely scenarios. In the children and adolescent studies, closed loop was used following a standard evening meal and following 40 min of moderate-intensity exercise. In the adult studies, closed loop was commenced following a 60 g carbohydrate meal or a 100 g carbohydrate meal accompanied by alcohol. The primary outcome measure was time for which plasma glucose was within target range (3.91–8.0 mmol/liter). Results: Overnight closed loop increased the time in target plasma glucose in both young (from 40% to 60%, p = .002) and adults (from 50% to 76%, p < .001) compared with conventional CSII. Combined analysis showed an increase from 43% to 71% with closed loop ( p < .001). Additionally, closed loop reduced the time spent below 3.91 mmol/liter and above 8.0 mmol/liter, from 4.1% to 2.1% ( p = .01) and 33% to 20% ( p = .03), respectively. Glycemic variability, as measured by the SD of plasma glucose, was lower during closed loop compared with CSII (1.5 versus 2.1 mmol/liter, p = .007). Conclusions: Overnight closed loop may improve glycemic control and reduce nocturnal hypoglycemia in both young people and adults with T1DM.
Generic Safety Requirements for Developing Safe Insulin Pump Software
Authors: Zhang Yi , Jetley Raoul , Jones Paul L. , Ray Arnab 
Published: January 2014

Background: The authors previously introduced a highly abstract generic insulin infusion pump (GIIP) model that identified common features and hazards shared by most insulin pumps on the market. The aim of this article is to extend our previous work on the GIIP model by articulating safety requirements that address the identified GIIP hazards. These safety requirements can be validated by manufacturers, and may ultimately serve as a safety reference for insulin pump software. Together, these two publications can serve as a basis for discussing insulin pump safety in the diabetes community. Method: In our previous work, we established a generic insulin pump architecture that abstracts functions common to many insulin pumps currently on the market and near-future pump designs. We then carried out a preliminary hazard analysis based on this architecture that included consultations with many domain experts. Further consultation with domain experts resulted in the safety requirements used in the modeling work presented in this article. Results: Generic safety requirements for the GIIP model are presented, as appropriate, in parameterized format to accommodate clinical practices or specific insulin pump criteria important to safe device performance. Conclusion: We believe that there is considerable value in having the diabetes, academic, and manufacturing communities consider and discuss these generic safety requirements. We hope that the communities will extend and revise them, make them more representative and comprehensive, experiment with them, and use them as a means for assessing the safety of insulin pump software designs. One potential use of these requirements is to integrate them into model-based engineering (MBE) software development methods. We believe, based on our experiences, that implementing safety requirements using MBE methods holds promise in reducing design/implementation flaws in insulin pump development and evolutionary processes, therefore improving overall safety of insulin pump software.
Glucose Control in Mayo Clinic Intensive Care Units
Authors: Pattan Vishwanath , Parsaik Ajay , Brown Julie K. , Kudva Yogish C. , Vlahakis Nicholas , Basu Ananda 
Published: January 2014

Background: Safe and effective glucose control in the intensive care unit (ICU) continues to be actively pursued. Large clinical trials have examined the safety and efficacy of insulin infusion protocols in medical and surgical ICUs. We report experiences of a single-center standardized nurse-driven insulin infusion protocol in three ICUs in an observational quality-improvement study. Method: We analyzed the hourly point-of-care arterial blood glucose obtained during ICU insulin infusion protocol (protocol A) with a glucose target of 80–130 mg/dl in medical and surgical ICUs in February 2009. Following Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study results, the protocol was amended (protocol B) to achieve target glucose of 110–150 mg/dl. The performance of protocol B was assessed in the ICUs in May 2010 and compared with protocol A with respect to glucose concentrations and rates of severe (<40 mg/dl) and moderate (40–60 mg/dl) hypoglycemia. Results: With protocol A, in medical ( n = 44) and surgical ( n = 164) ICUs taken together, median glucose was 119 mg/dl, with severe and moderate hypoglycemia rates 1.4% (3/208) and 7.7% (16/208), respectively, which were significantly lower than those reported by the NICE-SUGAR and the Leuven studies. With protocol B, in medical ( n = 44) and surgical ( n = 167) ICUs taken together, median glucose was 132 mg/dl, with severe and moderate hypoglycemia of 0 % (0/211) and 0.5% (1/211), respectively. Conclusion: The current ICU insulin infusion protocol (protocol B) reduces severe and moderate hypoglycemia without compromising glucose control when compared with protocol A. This could potentially impact patient-important outcomes.
Activation of Polymorphonuclear Leukocytes by Candidate Biomaterials for an Implantable Glucose Sensor
Authors: Sokolov Andrey , Hellerud Bernt Christian , Lambris John D. , Johannessen Erik A. , Mollnes Tom Eirik 
Published: January 2014

Background: Continuous monitoring of glucose by implantable microfabricated devices offers key advantages over current transcutaneous glucose sensors that limit usability due to their obtrusive nature and risk of infection. A successful sensory implant should be biocompatible and retain long-lasting function. Polymorphonuclear leukocytes (PMN) play a key role in the inflammatory system by releasing enzymes, cytokines, and reactive oxygen species, typically as a response to complement activation. The aim of this study was to perform an in vitro analysis of PMN activation as a marker for biocompatibility of materials and to evaluate the role of complement in the activation of PMN. Methods: Fifteen candidate materials of an implantable glucose sensor were incubated in lepirudin-anticoagulated whole blood. The cluster of differentiation molecule 11b (CD11b) expression on PMN was analyzed with flow cytometry and the myeloperoxidase (MPO) concentration in plasma was analyzed with enzyme-linked immunosorbent assay. Complement activation was prevented by the C3 inhibitor compstatin or the C5 inhibitor eculizumab. Results: Three of the biomaterials (cellulose ester, polyamide reverse osmosis membrane, and polyamide thin film membrane), all belonging to the membrane group, induced a substantial and significant increase in CD11b expression and MPO release. The changes were virtually identical for these two markers. Inhibition of complement with compstatin or eculizumab reduced the CD11b expression and MPO release dose dependently and in most cases back to baseline. The other 12 materials did not induce significant PMN activation. Conclusion: Three of the 15 candidate materials triggered PMN activation in a complement-dependent manner and should therefore be avoided for implementation in implantable microsensors.
Pancreatic Polypeptide Administration Enhances Insulin Sensitivity and Reduces the Insulin Requirement of Patients on Insulin Pump Therapy
Authors: Rabiee Atoosa , Galiatsatos Panagis , Salas-Carrillo Rocio , Thompson Michael J. , Andersen Dana K. , Elahi Dariush 
Published: January 2014

Introduction: The effects of pancreatic polypeptide (PP) infusion were examined in patients on insulin pump therapy to determine whether PP administration can reduce insulin requirements in patients with type 1 diabetes mellitus (T1DM) or type 3c diabetes mellitus (T3cDM; pancreatogenic). Methods: Ten subjects with long-standing T1DM ( n = 7)or T3cDM ( n = 3)on insulin pump treatment received a 72 h subcutaneous infusion of 2 pmol/kg/min bovine PP or saline by portable infusion pump in a single-blinded, randomized, crossover design. Results: Pancreatic polypeptide infusion raised plasma PP levels to 450–700 pmol/liter. Daily insulin infusion requirements (I) fell from 48 ± 6.9 to 40 ± 7.5 U on day 2 ( p < .05)and from 46 ± 7.7 to 37 ± 6.6 U on day 3 ( p < .05)of PP infusion compared with saline. Corrected for average blood glucose concentration (G), I/G fell in 10/10 subjects during the second 24 h period and in 7/10 subjects during the third 24 h period; sensitivity to insulin, calculated as 1/(I/G), increased 45% ± 12% on day 2 ( p < .01) and 34% ± 14% on day 3 ( p < .05) of PP infusion. Pancreatic polypeptide responses to a test meal were compared with the change in insulin infusion requirements in 5 subjects; The reduction in insulin requirements seen during PP infusion correlated with the degree of baseline PP deficiency ( p < .002). Conclusions: A concurrent subcutaneous infusion of PP enhances insulin sensitivity and reduces insulin requirements in patients with long-standing T1DM and T3cDM on insulin pump therapy. The benefit of PP infusion correlated with the degree of PP deficiency.
Consensus Report: The Current Role of Self-Monitoring of Blood Glucose in Non-Insulin-Treated Type 2 Diabetes
Authors: Klonoff David C. , Blonde Lawrence , Cembrowski George , Chacra Antonio Roberto , Charpentier Guillaume , Colagiuri Stephen , Dailey George , Gabbay Robert A. , Heinemann Lutz , Kerr David , Nicolucci Antonio , Polonsky William , Schnell Oliver , Vigersky Robert , Yale Jean-François 
Published: January 2014

The Coalition for Clinical Research—Self-Monitoring of Blood Glucose Scientific Board convened a meeting in San Francisco, CA, July 20–21, 2011, to discuss the current practice of self-monitoring of blood glucose (SMBG) in non-insulin-treated (NIT) type 2 diabetes mellitus (T2DM). Twelve physician panel members from academia, practice, and government attended this meeting. These experts came from the United States, Brazil, Canada, France, Germany, Italy, and the United Kingdom. In addition, three consultants from Australia, Germany, and the United States contributed to the group's final report. This coalition was organized by Diabetes Technology Society. Self-monitoring of blood glucose was studied from eight perspectives related to patients with NIT T2DM: (1) epidemiological studies; (2) randomized controlled trials (RCT)s and meta-analyses; (3) targets, timing, and frequency of SMBG use; (4) incidence and role of SMBG in preventing hypoglycemia with single-drug regimens and combination regimens consisting of antihyperglycemic agents other than secretagogues and insulin; (5) comparison of SMBG with continuous glucose monitoring; (6) technological capabilities and limitations of SMBG; (7) barriers to appropriate use of SMBG; and (8) methods and end points for appropriate future clinical trials. The panel emphasized recent studies, which reflect the current approach for applying this intervention. Among the participants there was consensus that: SMBG is an established practice for patients with NIT T2DM, and to be most effective, it should be performed in a structured format where information obtained from this measurement is used to guide treatment; New, high-quality efficacy data from RCTs have demonstrated efficacy of SMBG in NIT T2DM in trials reported since 2008; Both patients and health care professionals require education on how to respond to the data for SMBG to be effective; and Additional well-defined studies are needed to assess the benefits and costs of SMBG with end points not limited to hemoglobin A1c.
A Review of the Security of Insulin Pump Infusion Systems
Authors: Paul Nathanael , Kohno Tadayoshi , Klonoff David C. 
Published: January 2014

Insulin therapy has enabled patients with diabetes to maintain blood glucose control to lead healthier lives. Today, rather than injecting insulin manually using syringes, a patient can use a device such as an insulin pump to deliver insulin programmatically. This allows for more granular insulin delivery while attaining blood glucose control. Insulin pump system features have increasingly benefited patients, but the complexity of the resulting system has grown in parallel. As a result, security breaches that can negatively affect patient health are now possible. Rather than focus on the security of a single device, we concentrate on protecting the security of the entire system. In this article, we describe the security issues as they pertain to an insulin pump system that includes an embedded system of components, which include the insulin pump, continuous glucose management system, blood glucose monitor, and other associated devices (e.g., a mobile phone or personal computer). We detail not only the growing wireless communication threat in each system component, but also describe additional threats to the system (e.g., availability and integrity). Our goal is to help create a trustworthy infusion pump system that will ultimately strengthen pump safety, and we describe mitigating solutions to address identified security issues.
Association of Hyperglycemia, Glucocorticoids, and Insulin Use with Morbidity and Mortality in the Pediatric Intensive Care Unit
Authors: Wintergerst Kupper A. , Foster Michael B. , Sullivan Janice E. , Woods Charles R. 
Published: January 2014

Background: Studies of pediatric intensive care unit (PICU) patients have shown a significant association of morbidity and mortality with hyperglycemia. We retrospectively evaluated the degree of hyperglycemia as well as its correlation with glucocorticoid and insulin use and assessed its association with hospital length of stay (LOS) and mortality. This study preceded the initiation of a standard glycemic control protocol. Methods: We examined medical records at Kosair Children's Hospital for all PICU admissions from 2008 of patients without diabetes mellitus. Critical illness hyperglycemia (CIH) was defined by having three or more peak glucose values greater than thresholds of 110, 140, 180, and 200 mg/dl. These patients were evaluated for glucocorticoid, insulin use, and outcome measures. Results: We evaluated the eligible 1173 admissions, where 10.5% of these patients reached the highest threshold (200 mg/dl) of CIH. Glucocorticoids were used in 43% of these patients, with dexamethasone being the most common (58%). There was a significant correlation between glucocorticoids and higher peak glucose values, where 81% of the patients who were above the 200 mg/dl cutoff level were treated with glucocorticoids. Only 36.8% in that group were also treated with insulin. Patients at the 200 mg/dl cutoff had the highest median PICU and total hospital length of stays (4 and 10 days, respectfully). Mortality was associated with increasing glucose levels, reaching 18.7% among patients above the 200 mg/dl cutoff. Conclusion: Hyperglycemia was prevalent in the PICU and was associated with increased morbidity, as characterized by increased LOS and increased mortality. Glucocorticoid use was prevalent among patients exhibiting hyperglycemia. Insulin use was uncommon.
Effect of Disinfectants on Glucose Monitors
Authors: Mahoney John J. , Lim Christine G. 
Published: January 2014

Background: Monitoring blood glucose levels is an integral part of routine diabetes management. To minimize the risk of transmission of bloodborne pathogens during monitoring, the Centers for Disease Control and Prevention (CDC) recommends that glucose meters be disinfected after each use whenever they are used to test multiple patients. The objective of this study is to assess the compatibility of some common disinfectants with certain blood glucose meter systems. Methods: We tested six disinfectants for adverse impact on meter performance or the exterior meter surfaces. The disinfectants tested were 0.525% sodium hypochlorite, 20% 2-propanol and 10% ethanol, 17.2% isopropanol, 55% isopropanol, 70% isopropanol, and hydrogen peroxide. To assess meter performance, we tested OneTouch® Ultra® blood glucose monitoring systems with control solution before and after application of either water or disinfectant. To assess the effect on exterior meter surfaces, we performed a soaking test to simulate long-term exposure to disinfectant. Results: Paired t-test results showed that the control solution data associated with disinfectant and with water application were not significantly different for each meter type. However, most of the meter types were adversely affected by hydrogen peroxide and/or by the higher concentrations of alcohol-based disinfectants. Conclusions: Although none of the six disinfectants affected meter performance, hydrogen peroxide and isopropanol >20% adversely affected the exterior surfaces of the tested meters. When complying with CDC instructions for meter disinfection, users should use caution and choose disinfectants that have been validated by the meter manufacturer.
Noninvasive Measurement of Plasma Triglycerides and Free Fatty Acids from Exhaled Breath
Authors: Minh Timothy Do Chau , Oliver Stacy R. , Flores Rebecca L. , Ngo Jerry , Meinardi Simone , Carlson Matthew K. , Midyett Jason , Rowland F. Sherwood , Blake Donald R. , Galassetti Pietro Renato 
Published: January 2014

Background: Although altered metabolism has long been known to affect human breath, generating clinically usable metabolic tests from exhaled compounds has proven challenging. If developed, a breath-based lipid test would greatly simplify management of diabetes and serious pathological conditions (e.g., obesity, familial hyperlipidemia, and coronary artery disease), in which systemic lipid levels are a critical risk factor for onset and development of future cardiovascular events. Methods: We, therefore, induced controlled fluctuations of plasma lipids (insulin-induced lipid suppression or intravenous infusion of Intralipid) during 4-h in vivo experiments on 23 healthy volunteers (12 males/11 females, 28.0 ± 0.3 years) to find correlations between exhaled volatile organic compounds and plasma lipids. In each subject, plasma triglycerides (TG) and free fatty acids (FFA) concentrations were both directly measured and calculated via individualized prediction equations based on the multiple linear regression analysis of a cluster of 4 gases. In the lipid infusion protocol, we also generated common prediction equations using a maximum of 10 gases. Results: This analysis yielded strong correlations between measured and predicted values during both lipid suppression ( r = 0.97 for TG; r = 0.90 for FFA) and lipid infusion ( r = 0.97 for TG; r = 0.94 for FFA) studies. In our most accurate common prediction model, measured and predicted TG and FFA values also displayed very strong statistical agreement ( r = 0.86 and r = 0.81, respectively). Conclusions: Our results demonstrate the feasibility of measuring plasma lipids through breath analysis. Optimization of this technology may ultimately lead to the development of portable breath analyzers for plasma lipids, replacing blood-based bioassays.