bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of Electronic Diaries in Diabetes Clinical Trials Measured through Overall Satisfaction of Site Coordinators
Authors: Jhaveri Mehul , Lee Elizabeth
Published: January 2014

Background:

Clinical trials are increasingly being designed to collect data directly from patients through the use of paper diaries or electronic diaries (e-diaries). E-diaries can be advantageous over paper diaries, but actual benefits may depend on the particular features of a given e-diary. The objective of this study was to determine which e-diary system features are most important to consider when selecting such a tool.

Methods:

A 42-question survey was distributed to 295 site coordinators participating in four diabetes clinical trials, using e-diary systems provided by three different vendors. The survey gathered information about the site coordinators' experience with the e-diary system used. Analyses included a comparison of global satisfaction rating scores and individual survey item responses among the different e-diaries utilized and correlation of individual survey items with the global satisfaction rating for each system.

Results:

The survey was completed by 131 site coordinators (44% response rate). Mean global satisfaction rating scores varied from 3.4 to 7.2 ( p < 0.0001). Individual survey items such as technical problems that cannot be resolved easily, the ability of the help line to fully address problems, and organization and user-friendliness of the e-diary's data management Web site were most closely correlated with the global satisfaction rating. The site coordinators' prior e-diary experience and years of job experience did not significantly correlate with the global satisfaction rating.

Conclusions:

This survey highlights features of e-diaries for sponsors to consider in clinical trials, including the importance of minimizing technical problems, assessing vendors' help line capabilities, and choosing an e-diary system with an efficient and user-friendly data-management Web site.
Quantitation of Humalog Insulin by Reversed-Phase High-Performance Liquid Chromatography
Authors: Munsick Carey , Murray Robert , Dziubla Tom , Lowman Anthony M. , Joseph Jeffrey I. , Torjman Marc C.
Published: January 2014

Introduction:

The methodology for in vitro testing of insulin delivery systems for long-term infusion of lispro insulin requires insulin flow studies over time, with the measurement of lispro concentrations in wells or other laboratory fluid collection systems. We postulated that the efficiency of the insulin assay could be improved if the insulin collected in the wells could be measured without having to perform dilutions of insulin samples. The manufacturer's method for the identification of Humalog® insulin by high-performance liquid chromatography (HPLC) does not provide a detailed method for the quantitation of the clinical formulation. No reports could be found in the literature describing a method to quantitate lispro insulin's entire concentration range, nor could we find detailed information on pH effects. The purpose of this study was to investigate the use of a reversed-phase HPLC method to quantitate Humalog insulin at three levels of pH.

Methods:

Serial dilutions of Humalog insulin stock solution were prepared at pH levels of 2.6 and 7.4 (concentrations 0.20–100 IU/ml) to construct calibration curves. Samples were also prepared at lower concentrations (0.2315.0 IU/ml) at pH levels of 4.0 and 7.4. Areas under curve data were plotted against known concentrations, and the limit of quantitation and precision of the assay were determined.

Results:

Calibration curves for the 0.20–100 IU/ml concentration (pH 7.4 and 2.6) revealed no significant differences ( p < 0.01) between those curves. pH and concentration did not have an effect on the overall precision of the method. Linearity was not conserved past the 15-IU/ml concentration. Coefficient of variation (CV) values were generally <15% except at the lower concentrations where the largest CVs were observed. Mean known concentrations plotted on a logarithmic scale demonstrated linearity from 12.5 to 100 IU/ml.

Conclusions:

Humalog insulin clinical formulation can be quantitated over the entire concentration range by a reversed-phase HPLC method using nonlinear regression analysis. The method is reproducible at lower (<15 IU/ml) and higher insulin concentrations. Linear regression analysis may be used when the concentrations of interest are in the 0- to 15-IU range. Preparation of insulin solutions at pH 2.6, 4.0, and 7.4 did not significantly affect the reproducibility of the assay.
Putative Delays in Interstitial Fluid (ISF) Glucose Kinetics Can Be Attributed to the Glucose Sensing Systems Used to Measure Them Rather than the Delay in ISF Glucose Itself
Authors: Voskanyan Gayane , Keenan D. Barry , Mastrototaro John J. , Steil Garry M.
Published: January 2014

Background:

Since the advent of subcutaneous glucose sensors, there has been intense focus on characterizing the delay in the interstitial fluid (ISF) glucose response and the effect of insulin to alter the plasma-to-ISF glucose gradient. The Medtronic MiniMed continuous glucose monitoring system (CGMS) has often been used for this purpose; however, many of the studies have used experimental conditions that fall outside its intended use, for example, studies that have assessed the delay during rapid glucose excursions brought about by intravenous infusion of glucose or insulin. Under these conditions, it is possible that the rate of glucose change may exceed that allowed by CGMS filtering routines. If so, the estimated delay may be because of the filter rather than the ISF. Also, sensor characteristics, such as nonspecific offset current or stability, may have been inadvertently attributed to changes in the plasma-to-ISF gradient. The potential for these issues to have confounded the understanding of ISF glucose delay and gradient is investigated.

Methods:

An in vitro preparation in which no delay or gradient exists between sensor and measurement solution was used to recreate a rapidly changing glucose profile from a previously published in vivo study. The CGMS system (N = 6 sensors) was then used to estimate any artifactual delay and gradient introduced by the system per se.

Results:

One-point calibration resulted in an apparent change in gradient as glucose was lowered from ∼100 to 50 mg/dl. After a two-point calibration, sensor glucose followed the glucose profile as it was decreased slowly from ∼100 to ∼60 mg/dl; however, when the glucose level was subsequently increased rapidly to ∼150 mg/dl, CGMS filtering routines limited the rate of change of sensor glucose and introduced a delay similar to that previously attributed to ISF glucose equilibration delay.

Conclusions:

Studies that have previously used the Medtronic MiniMed CGMS system to assess changes in the plasma-to-ISF glucose gradient may need to be reassessed to ensure that the offset current was estimated accurately. Studies that have used the system to assess ISF glucose delay during rapid, unphysiologic changes in glucose and did not remove the CGMS smoothing filters may have attributed CGMS filter delay to ISF glucose equilibration.
Comparison of Patient's Preference, Pain Perception, and Usability between Micro Fine plus® 31-Gauge Needle and Microtapered NanoPass® 33-Gauge Needle for Insulin Therapy
Authors: Miyakoshi Masashi , Kamoi Kyuzi , Iwanaga Midori , Hoshiyama Ayako , Yamada Ayako
Published: January 2014

Background:

How smoothly insulin is injected is one of the major concerns when patients commence insulin injection therapy. Improving its usability may be important in initiation therapy and adherence, resulting in clinical

Methods:

In a single-center, open-label and randomized two-period crossover trial, the effect of the tapered needle of NanoPass® (33 gauge, 5 mm) on usability in comparison with the standard needle of Micro Fine Plus® (31 gauge, 5 mm) was examined using a questionnaire. Patients with insulin-dependent diabetes ( n = 40, self-injecting insulin four times daily for more than 3 months) were randomized to use NanoPass or Micro Fine Plus needles for 1 week and then use the alternative for 1 week. Patients completed the questionnaire before and after each test week. Each evaluation was scored from −100 (worst) to +100 (best) by a visual analogue scale. A higher score indicated a more favorable outcome compared with the other needle.

Results:

The NanoPass needles. Meanwhile, the NanoPass needle, which had less resistance in insertion with a new lubricant coating P < 0.001) overall patient's satisfaction score, including less frightening use, less bleeding, and less dribbling of injected insulin in comparison with the former evaluation.

Conclusions:

For overall patient satisfaction in using an insulin needle, developing a thinner needle and improving other factors, such as lubricity coating the needle, are important.
Physical Activity Monitors: Do More Sensors Mean Better Precision?
Authors: Chen Kong Y. , Rothney Megan P. , Brychta Robert J.
Published: January 2014

Physical activity is essential to health. Accelerometry-based activity monitors are widely used in clinical and epidemiological research settings; however, only measuring body movement may prohibit accurate prediction of energy expenditure. Recent technological advancements allow synchronous measurements of heart rate, body temperature, acceleration, and other physiological responses and record them in detail (every minute or finer precision). Current multisensor devices are small, wireless, and capable of continuously recording data over several days or weeks, making them readily applicable in the free-living environment. Future studies should focus on developing strategies to optimize sensor data for accurate and robust predictions of clinically pertinent outcome parameters, such as total daily energy expenditure and physical activity energy expenditure. There is also a need for calibration instruments to allow users to standardize devices in their own laboratory or clinic. We also call for more transparency in publishing sensor properties and modeling algorithms, rather than proprietary or “black-box” prediction approaches.
Model Predictive Control of Type 1 Diabetes: An in Silico Trial
Authors: Magni Lalo , Raimondo Davide M. , Bossi Luca , Dalla Man Chiara , De Nicolao Giuseppe , Kovatchev Boris , Cobelli Claudio
Published: January 2014

Background:

The development of artificial pancreas has received a new impulse from recent technological advancements in subcutaneous continuous glucose monitoring and subcutaneous insulin pump delivery systems. However, the availability of innovative sensors and actuators, although essential, does not guarantee optimal glycemic regulation. Closed-loop control of blood glucose levels still poses technological challenges to the automatic control expert, most notable of which are the inevitable time delays between glucose sensing and insulin actuation.

Methods:

A new in silico model is exploited for both design and validation of a linear model predictive control (MPC) glucose control system. The starting point is a recently developed meal glucose-insulin model in health, which is modified to describe the metabolic dynamics of a person with type 1 diabetes mellitus. The population distribution of the model parameters originally obtained in healthy 204 patients is modified to describe diabetic patients. Individual models of virtual patients are extracted from this distribution. A discrete-time MPC is designed for all the virtual patients from a unique input-output-linearized approximation of the full model based on the average population values of the parameters. The in silico trial simulates 4 consecutive days, during which the patient receives breakfast, lunch, and dinner each day.

Results:

Provided that the regulator undergoes some individual tuning, satisfactory results are obtained even if the control design relies solely on the average patient model. Only the weight on the glucose concentration error needs to be tuned in a quite straightforward and intuitive way. The ability of the MPC to take advantage of meal announcement information is demonstrated. Imperfect knowledge of the amount of ingested glucose causes only marginal deterioration of performance. In general, MPC results in better regulation than proportional integral derivative, limiting significantly the oscillation of glucose levels.

Conclusions:

The proposed in silico trial shows the potential of MPC for artificial pancreas design. The main features are a capability to consider meal announcement information, delay compensation, and simplicity of tuning and implementation.
Glucose Estimation and Prediction through Meal Responses Using Ambulatory Subject Data for Advisory Mode Model Predictive Control
Authors: Gillis Rachel , Palerm Cesar C. , Zisser Howard , Jovanovic Lois , Seborg Dale E. , Doyle Francis J.
Published: January 2014

Background:

A primary challenge for closed-loop glucose control in type 1 diabetes mellitus (T1DM) is the development of a control strategy that will be applicable during all daily activities, including meals, stress, and exercise. A model-based control algorithm requires a mathematical model that has the simplicity for online glucose prediction, yet retains the complexity necessary to cope with variations in insulin sensitivities and carbohydrate ingestion.

Methods:

A modified Bergman minimal model was linearized for Kalman filter (KF) state estimation on data from T1DM subjects, and multiple methods of parameter augmentation were developed for online adaptation. In addition, model deterioration for glucose prediction was assessed to determine an appropriate prediction horizon for model predictive control (MPC). Furthermore, MPC strategies were validated using advisory mode simulations.

Results:

Twenty days of continuous glucose data, which included 97 meals, were evaluated for three subjects. A constant parameter minimal model was used to predict glucose levels for normal days with meal announcement and with a maximum prediction horizon of approximately 45 minutes. In order to attain this prediction horizon in the absence of meal announcement, parameter adaptation was necessary to capture the glucose disturbance. Evaluation of advisory mode MPC permitted effective tuning for a moderately aggressive controller that responded well to meal disturbances.

Conclusions:

Estimation and prediction of glucose were accomplished using a KF based on a modified Bergman model. For a model with no meal announcement, parameter adaptation provided the means for closed-loop implementation. This state estimation and model validation scheme established the necessary framework for advisory mode MPC.
Blood-Induced Interference of Glucose Sensor Function in Vitro: Implications for in Vivo Sensor Function
Authors: Klueh Ulrike , Liu Zenghe , Ouyang Tianmei , Cho Brian , Feldman Ben , Henning Timothy P. , Kreutzer Don
Published: January 2014

Background:

Although tissue hemorrhages, with resulting blood clots, are associated with glucose sensor implantation, virtually nothing known is about the impact of red blood cells and red blood cell clots on sensor function in vitro or in vivo. In these studies, we tested the hypothesis that blood can directly interfere with glucose sensor function in vitro.

Methods:

To test this hypothesis, heparinized human whole blood (HWB) and nonheparinized human whole blood (WB) were obtained from normal individuals. Aliquots of HWB and WB samples were also fractionated into plasma, serum, and total leukocyte (TL) components. Resulting HWB, WB, and WB components were incubated in vitro with an amperometric glucose sensor for 24 hours at 37°C. During incubation, blood glucose levels were determined periodically using a glucose monitor, and glucose sensor function (GSF) was monitored continuously as nanoampere output.

Results:

Heparinized human whole blood had no significant effect on GSF in vitro, nor did TL, serum, or plasma-derived clots from WB. Sensors incubated with WB displayed a rapid signal loss associated with clot formation at 37°C. The half-life was 0.8 ± 0.2 hours (n = 16) for sensors incubated with WB compared to 3.2 ± 0.5 (n = 12) for sensors incubated with HWB with a blood glucose level of approximately 100 mg/dl.

Conclusion:

These studies demonstrated that human whole blood interfered with GSF in vitro. These studies further demonstrated that this interference was related to blood clot formation, as HWB, serum, plasma-derived clots, or TL did not interfere with GSF in vitro in the same way that WB did. These in vitro studies supported the concept that the formation of blood clots at sites of glucose sensor implantation could have a negative impact on GSF in vivo.
A1cNow® InView™: A New Simple Method for Office-Based Glycohemoglobin Measurement
Authors: Mattewal Amarbir , Aldasouqi Saleh , Solomon David , Gossain Ved , Koller Anthony
Published: January 2014

Background:

Glycohemoglobin A1c (HbAlc) is a universally accepted tool for glycemic control. Portable HbAlc devices for use in physicians' offices are desirable because they provide immediate results that physicians can share with their patients. This has been shown to enhance self-management in patients with diabetes. We undertook this study to evaluate the accuracy and precision of a recently introduced device, the AlcNow® InView™ capillary monitor.

Method:

Previously tested EDTA-preserved whole blood samples from our laboratory pool were preselected based on the results of HbAlc to cover a range from 4 to 13%. HbAlc was then measured using an AlcNow InView capillary monitor. Blinded aliquots of these samples were then sent to a National Glycohemoglobin Standardization Program (NGSP)-certified reference laboratory for comparison. One sample with a laboratory HbAlc result of 9.2% was measured with the InView device nine successive times to assess the device precision. The consistency between the measurement of HbAlc measured by the reference laboratory and the AlcNow InView device was analyzed via linear regression.

Results:

Thirty-five samples were tested. The correlation between HbAlc measured by the InView device and the reference laboratory, as well as our own laboratory, was 0.96. The coefficient of variation was 2.7l°%.

Conclusions:

Results of this study confirm the accuracy and precision of the InView capillary HbAlc monitor. However, the feasibility, reproducibility, and cost-effectiveness of this promising device in the real-life settings of physicians' offices must be verified by prospective clinical studies.
Diabetes Data Management in the Clinic
Authors: Bailey Timothy S.
Published: January 2014

Diabetes data management using a computer has not been widely adopted, even among diabetes-focused professionals. Barriers to adoption include incompatible devices and protocols, time and effort required, and lack of specific reimbursement. A simplified approach used at our clinic to review diabetes data is presented.
Parameters Affecting Postprandial Blood Glucose: Effects of Blood Glucose Measurement Errors
Authors: Koschinsky Theodor , Heckermann Sascha , Heinemann Lutz
Published: January 2014

Background:

The Diabetes Error Test Model (DETM) has been developed to characterize the clinical relevance of the large and varying margins of error of parameters affecting postprandial blood glucose (BG) levels, which increase the risk for hypo- or hyperglycemia.

Methods:

The DETM is based on a treatment concept aimed at normoglycemia after meals. The model includes as parameters (a) preprandial BG measurement by patient self-monitoring (SMBG), (b) patient estimate of carbohydrate amounts (CARB-P) in food, (c) effect of CARB-P on maximum BG increase, (d) effect of insulin on maximum BG decrease, and (e) insulin dosage. Covering the relevant range of preprandial BG (30–330 mg/dl), the DETM simulates the maximum effect of these parameters and their margins of error on postprandial BG values.

Results:

According to the DETM, a SMBG error of +20% results in normoglycemia (BG range: 60–160 mg/dl) as the postprandial outcome if preprandial BG values are in the range of 30–130 or 260–330 mg/dl, but can unexpectedly result in hypoglycemia if preprandial BG values are between 131 and 259 mg/dl. If the SMBG error of +20% is combined, e.g., with an error of CARB-P estimate in the food of +20%, hypoglycemia as the postprandial outcome is worsened. If one combines the effects of errors of more than two parameters, even with errors that are so small that they have no clinically relevant dysglycemic effect on postprandial BG per se (e.g., ±6%), this can result in postprandial hypo- or hyperglycemic values.

Conclusion:

The DETM simulates the effects of errors of parameters affecting postprandial BG within the clinically relevant BG range. The DETM offers the opportunity to evaluate the clinical relevance of these errors and their contribution to the increased risk of meal-related excessive glucose excursions during intensified insulin therapy.
Practical Experience with Continuous Subcutaneous Insulin Infusion Therapy in a Pediatric Diabetes Clinic
Authors: O'Connell Michele A. , Cameron Fergus J.
Published: January 2014

Continuous subcutaneous insulin infusion therapy (CSII) is an increasingly popular form of intensive insulin administration in pediatric patients. The use of CSII commenced at our large tertiary referral diabetes clinic as recently as 2002. In the intervening years, demand and enthusiasm from both patients and physicians alike have resulted in a steady ongoing increase in CSII use at our clinic. We currently have >200 active patients using insulin pump therapy. This article reviews our experience with CSII and outlines our current multidisciplinary approach to optimizing glycemic control and outcomes in this patient group.
Development of an Internet/Population-Based Weight Management Program for the U.S. Army
Authors: Stewart Tiffany , May Sandra , Allen H. Raymond , Bathalon Gaston P. , Lavergne Guy , Sigrist Lori , Ryan Donna , Williamson Donald A.
Published: January 2014

A significant number of Army soldiers are sufficiently overweight to exceed the maximum weight allowances defined by the Army weight control program (AR600–9). Also, the body weights of a substantial number of soldiers approach the maximum weight allowances. These soldiers should not gain additional weight if they are to meet Army weight allowances. The conventional approach to this overweight problem is assigning soldiers to remedial physical training and mandatory referral for nutrition counseling by a health care provider. An alternative to this conventional approach is to target the entire population of soldiers (population-based intervention) to promote weight loss in overweight soldiers and weight gain prevention in soldiers who are approaching overweight status. To accomplish this objective, the Healthy Eating, Activity, and Lifestyle Training Headquarters (H.E.A.L.T.H.) program was developed. This article describes the rationale for developing the program, the components of the program, and the utilization promotion strategies of the program. The H.E.A.L.T.H. program includes two primary components: (1) a Web site tailored to the standards established in Field Manual 21–20, Physical Fitness Training, Army physical fitness test, and AR600-9, the army weight control program, and (2) a health promotion program designed to promote awareness of the H.E.A.L.T.H. Web site and to facilitate use of the Web site by soldiers and their family members. The Web site is equipped with personalized planning tools and progress tracking over time related to fitness, caloric intake, and lifestyle behavior change goals. The health promotion program includes media advertisements and “ground roots” efforts to facilitate use by soldiers.
Novel Interactive Cell-Phone Technology for Health Enhancement
Authors: Katz David L. , Nordwall Bjorn
Published: January 2014

Self-care is essential in chronic disease management; however, adherence to self-care plans is often far from optimal. Advances in technology can facilitate self-management of chronic disease through patient empowerment and timely feedback. The Confidant system is a novel wireless remote patient monitoring and response system, centered around mobile phone technology, that translates scientifically supported knowledge for chronic disease management into action by providing easily followed daily coaching using the patient's own data. Daily provision of interactive, informative messages removes the burdens of recall, record keeping, decision making, scheduling, and data analysis. A pilot-controlled clinical trial evaluated the feasibility and efficacy of the Confidant system in the management of type 2 diabetes in 15 patients utilizing the cell-phone technology and 15 individuals in a control group (standard type 2 diabetes care). The study demonstrated improved levels of glycosylated hemoglobin, positive changes in diabetes management self-efficacy, and diabetes self-care activities among intervention group patients. A larger trial is now in development to demonstrate the clinical benefit of using the Confidant system among type 2 diabetic patients. This article describes the novel technology and applications of the Confidant system.
Glucose Monitoring in Acute Care: Technologies on the Horizon
Authors: Torjman Marc C. , Dalal Niti , Goldberg Michael E.
Published: January 2014

Current glucose monitoring technology appears inadequate for the management of diabetic surgical and in critically ill patients requiring intensive insulin therapy. Subcutaneous sensors measure interstitial fluid glucose, and this technology has not yet been shown to provide the timely and accurate measurements necessary for intravenous insulin administration in surgical and critical care patients on intensive insulin therapy. Technologies under development that may be more suitable for surgical and intensive care unit patients are the automated intermittent type glucose monitors and central catheter glucose monitors. Improved accuracy, patient safety, incorporation of control algorithms, and alleviation of added nursing labor are important factors for consideration with future acute care glucose monitors. Hospital costs for these monitors are difficult to estimate but may be relatively low if their use can be related to better patient outcome, reduced labor costs, and increased job satisfaction for the nursing staff.
An Analysis: Hyperglycemic Intensive Care Patients Need Continuous Glucose Monitoring—Easier Said than Done
Authors: Fahy Brenda G. , Coursin Douglas B.
Published: January 2014

Experts and agencies increasingly advocate tight glycemic control (TGC) using intensive intravenous insulin therapy in critically ill patients. Questions remain about the “best” glucose goal, the universal benefit of TGC in the heterogeneous adult intensive care unit (ICU) population, and concerns about the underrecognized incidence of hypoglycemia and its neuropsychological sequelae. TGC is time-consuming for ICU staff, and pathophysiologic, technical, and personnel factors impact the accuracy of point-of-care glucose monitoring. TGC in the ICU requires safe, accurate, robust, rapid, and continuous glucose measurements (CGM) that lack interference from drugs or other substances. Establishment of reliable CGM may provide the foundation for a closed loop, microprocessed system resulting in an artificial islet cell. This commentary focuses on reports from two respected groups on the potential use of CGM devices in the critically ill. It emphasizes the challenges of applying this technology in the ICU and looks to future refinements to address them.
How Much Do Forgotten Insulin Injections Matter to Hemoglobin A1c in People with Diabetes? a Simulation Study
Authors: Randløv Jette , Poulsen Jens Ulrik
Published: January 2014

Background:

Forgotten or omitted insulin injections are an important contributing factor to poor glycemic control in people with type 1 diabetes. This study uses mathematical modeling and examines the impact on hemoglobin A1c (HbA1c) levels if insulin injections are forgotten. The simulation concerns people with type 1 diabetes on intensive insulin therapy.

Methods:

Five sets of blood glucose profiles with and without a forgotten injection were obtained. The difference to HbA1c was calculated using an HbA1c estimator on the profiles and was multiplied by the frequency of forgotten events. A frequency of 2.1 forgotten injections per week was found in the literature.

Results:

Calculations showed that forgetting 2.1 meal-related injections per week would lead to an increase in HbA1c of at least 0.3–0.4% points, and similarly 0.2–0.3% points related to forgotten injections of the long-acting insulin. In case of even more pronounced nonadherence (e.g., if 39% of all injections are forgotten) there is a possible increase of HbA1c of 1.8% points.

Conclusions:

The magnitude of the possible improvement in HbA1c agrees well with other studies in the relation between adherence and HbA1c levels. The estimated numbers suggest that missing injections are an important reason for suboptimal treatment.
Analysis of the Use of Dried Blood Spot Measurements in Disease Screening
Authors: Lakshmy Ramakrishnan
Published: January 2014

The collection of dried blood spots on filter paper offers a powerful tool in screening programs and in large population-based surveys. The method has the advantage of being less invasive and relatively painless and is particularly suitable for collection in neonates and the elderly. Blood can be collected and transported economically without requiring a cold chain. The use of blood spots for the measurement of insulin, high sensitivity C-reactive protein, and triglycerides is reported. A good correlation between measurement of these analytes in dried blood and sera suggests that the method is valid and has the potential to be used for the screening of cardiometabolic risk factors. This method of blood collection is particularly suited for developing countries where cost cutting is important.
Combining Insulin Pumps and Continuous Glucose Monitors; Where Are We to Go from Here?
Authors: DeVries J. Hans
Published: January 2014

Insulin pump development started in 1978, with the first commercially available glucose sensor marketed in 1999. Combining these two instruments is a logical step toward the closed loop. This article discusses three questions: Is pump development complete? How can a pump and a sensor be combined? Can the delay problem associated with the subcutaneous-subcutaneous approach for the closed loop be overcome?
Utilization of Nerve Conduction Studies for the Diagnosis of Polyneuropathy in Patients with Diabetes: A Retrospective Analysis of a Large Patient Series
Authors: Kong Xuan , Lesser Eugene A. , Potts Frisso A. , Gozani Shai N.
Published: January 2014

Background:

Diabetic polyneuropathy (DPN) is a disabling complication of diabetes mellitus. A population-based analysis of physician utilization of nerve conduction studies (NCS) for the assessment of DPN was conducted.

Methods:

All electrodiagnostic encounters over a 30-month period using a computer-based neurodiagnostic instrument linked to a data registry were analyzed retrospectively. The DPN case definition was abnormal sural and peroneal nerve conduction.

Results:

The study cohort consisted of a total of 63,779 electrodiagnostic encounters performed by 3468 physician practices. Primary care and internal medicine physicians represented 80.1% of the practices and accounted for 65.7% of the encounters. Endocrinologists represented 4.6% of the practices and 20.1% of the encounters. The demographics of patients were 52.7% female; 63.4 ± 11.8 (mean ± standard deviation) years (age); 168.1 ± 10.9 cm (height); 92.2 ± 22.6 kg (weight); and 32.6 ± 7.2 kg/m2 (body mass index). The most common peroneal abnormality was F-wave latency (33.6%). The sural nerve response latency and amplitude parameters had similar abnormality rates (58.3 and 62.7%). DPN was identified in 52.6% of the encounters; in another 19.3% no neuropathy was found.

Conclusions:

For over 70% of the patients, the specific diagnostic question of the presence of DPN was addressed by NCS with evidence-based criteria. The demographic features were strongly associated with risk of diabetes and DPN, suggesting that NCS were applied to appropriate demographic subgroups. The rate of DPN was also comparable to levels seen by academic electromyography laboratories. In 32.6% of the encounters the NCS suggested a posttest diagnosis other than DPN. This rate was similar to the results of referral to traditional electromyography laboratories. This study demonstrated that NCS using computer-based electrodiagnostic equipment was a suitable tool for the diagnosis of DPN. Furthermore, this technology permits examination of DPN in large populations.
Improving Hyperglycemia in the Hospital: Outcomes of a Nursing In-Service to Evaluate Acceptance of a Web-Based Insulin Infusion Calculator
Authors: Hermayer Kathie L. , Hushion Timothy V. , Arnold Pamela C. , Wojciechowski Barbara
Published: January 2014

Background:

Many insulin infusion protocols are available for clinical use. We developed a Web-based, online intravenous insulin infusion calculator (IVIIC) for use in our intensive care and medical—surgical units.

Methods:

In September 2006, we implemented a quality improvement project: an online survey to evaluate the acceptance of this protocol by the nursing staff. Of the 103 registered nurses (RNs) who participated, there was no difference among experience levels of the RNs (≥ or <5 years) or among durations that RNs had been working within their unit (≥ or <2 years).

Results:

The nurses were surveyed regarding the use and interpretation of the protocol, their comfort with, confidence in, and experience in using the protocol. More than 80% of the RNs found the protocol easy to implement, easy to interpret, and successful in controlling the blood glucose levels. Approximately 71% (±9%) of the RNs were comfortable with the tight blood glucose levels of the protocol. The nurses' confidence with the protocol was 82% (±8%), likely because 70% (±9%) of the nurses believed the training to be adequate. Significantly less than 25% of the RNs (18 ± 7%) believed it was necessary to deviate from the protocol. More than 85% of the RNs appreciated the ability to make changes at their level of practice (92 ± 5%).

Conclusions:

In summary, the IVIIC is well accepted by RNs for care of hyperglycemia in a hospital setting.
Improvement in Glycemic Control and Outcome Corresponding to Intensive Insulin Therapy Protocol Development
Authors: Shulman Rob , Finney Simon J. , Shah Neelam , Ali Md Shawkat , Greene Russell , Glynne Paul A.
Published: January 2014

Background:

Intensive insulin therapy (IIT) has been shown to reduce mortality and morbidity in longer stay, critically ill patients. However, this has been demonstrated in a single site, whereas two multicentric studies have been terminated prematurely mainly due to hypoglycemia. Other difficulties with IIT include efficacy of glycemic control. This report describes how IIT can be improved by protocol simplification and removal of glucose supplementation.

Methods:

A clinical information system established at each bedspace guided staff through the IIT algorithms. Time spent within predefined glycemic ranges was calculated assuming a linear trend between successive measurements. Three groups were investigated retrospectively: IIT1 protocol,1 an updated IIT2 version, and intuitive nurse dosing of conventional insulin therapy (CIT).

Results:

Fifty consecutive, critically ill patients were included in each study group. Patient characteristics were similar in each group. The frequency of CIT and IIT2 blood glucose measurements were 11.6 and 11.5 measurements per day, respectively, while the IIT1 measurements were more frequent (14.5 measurements per day). The mean proportion of time spent in the target glycemic range (4.4–6.1 mmol/liter) was highest in the IIT2 group (34.9%), as compared to the IIT1 (22.9%) and CIT groups (20.3%) ( p <.001). Survival at 28 days was 74.5% for IIT2 (highest), 68% for IIT1, and 48% for CIT ( p = .02). There were a similar number of those experiencing a severe hypoglycemic event in each group.

Conclusions:

IIT protocol optimization was associated with increased glycemic control and improved 28–day survival. The better optimized IIT2 protocol provided tighter control than either the IIT1 or CIT protocol, without increased sampling or incidence of hypoglycemia. The clinical effectiveness of the IIT algorithm appeared to be improved by simplifying the protocol to meet the needs of the critical care unit.
In Silico Testing—Impact on the Progress of the Closed Loop Insulin Infusion for Critically Ill Patients Project
Authors: Wilinska Malgorzata E. , Chassin Ludovic J. , Hovorka Roman
Published: January 2014

Background:

In silico testing was used extensively in the European Commission-funded Closed Loop Insulin Infusion for Critically Ill Patients (Clinicip) project, which aimed to develop prototype systems for closed loop glucose control in the critically ill. This article presents two examples of how the simulation environment was utilized in this project.

Methods:

The in silico simulation environment was used to simulate a 48-hour clinical trial in a surgical intensive care unit to achieve tight glycemic control. A set of 10 critically ill synthetic subjects was selected for two different studies. In the first study, two sets of clinical trials were simulated using two versions of a model predictive control (MPC)-based glucose control algorithm: MPC Version 0.1.5 with hourly glucose measurements and updated MPC Version 1.4.3 with variable 1- to 4-hour glucose sampling. In the second study, four sets of clinical trials were simulated with four levels of measurement error at 2, 5, 7, and 15% coefficient of variation corresponding to the measurement error of commercially available glucose measuring devices.

Results:

In the first study, more frequent glucose measurements associated with MPC Version 0.1.5 facilitated more efficacious and safer glucose control compared to that obtained with the prolonged and variable glucose sampling rate associated with MPC Version 1.4.3. In the second study, a marked deterioration in safety measures was observed in studies performed with a measurement error of 15%.

Conclusions:

The presented simulation studies highlighted two important uses of in silico simulation environment in the Clinicip project. The impressive progress and successful completion of the Clinicip project would not be possible without computer-based simulations.
Model-Based Insulin Sensitivity as a Sepsis Diagnostic in Critical Care
Authors: Blakemore Amy , Wang Sheng-Hui , Le Compte Aaron , Shaw Geoffrey M. , Wong Xing-Wei , Lin Jessica , Lotz Thomas , Hann Christopher E. , Chase J. Geoffrey
Published: January 2014

Background:

Timely diagnosis and treatment of sepsis in critical care require significant clinical effort, experience, and resources. Insulin sensitivity is known to decrease with worsening condition and could thus be used to aid diagnosis. Some glycemic control protocols are able to identify insulin sensitivity in real time.

Methods:

Receiver operating characteristic curves and cutoff insulin sensitivity values for diagnosing sepsis were calculated for model-based insulin sensitivity ( S I) and a simpler metric ( SS I) that was estimated from glycemic control data of 30 patients with sepsis and can be calculated in real time without use of a computer. Results were compared to the insulin sensitivity profiles of a general intensive care unit population of 113 patients without sepsis and 30 patients with sepsis, comprising a total of 26,453 patient hours. Patients with sepsis were identified as having sepsis based on a sepsis score ( ss) of 3 or higher ( ss = 0–4 for increasing severity). Patients with type I or type II diabetes were excluded. Ethics approval for this study was granted by the South Island Regional Ethics Committee.

Results:

Receiver operating characteristic cutoff values of S I = 8 × 10–5 liter mU−1 min−1 and SS I = 2.8 × 10−4 liter mU−1 min−1 were determined for ss ≥ 3. The model-based S I fell below this value in 15% of all patient hours. The S I test had a negative predictive value of 99.8%. The test sensitivity was 78% and specificity was 82%. However, the positive predictor value was 2.8%. Slightly lower sensitivity (68.8%) and specificity (81.7%), but equally good negative prediction (99.7%), were obtained for the estimated SS I.

Conclusions:

Insulin sensitivity provides a negative predictive diagnostic for sepsis. High insulin sensitivity rules out sepsis for the majority of patient hours and may be determined noninvasively in real time from glycemic control protocol data. Low insulin sensitivity is not an effective diagnostic, as it can equally mark the presence of sepsis or other conditions.
Continuous Glucose Monitoring Awaits Its “Killer App”
Authors: Russell Steven J.
Published: January 2014

Continuous glucose monitoring (CGM) could drive a paradigm shift in diabetes care, but realization of this promise awaits a complementary shift in the way CGM data is used. The most exciting use for CGM is as the input for automated, closed-loop glucose control. Although first generation CGM devices leave much room for improvement, closed-loop control does not have to wait. Algorithms should target blood glucose levels above the normal range for safety in the setting of imperfect CGM measurements. If the mean glucose under closed-loop control is sufficiently close to the chosen target, hemoglobin A1c goals could be met while minimizing risk of hypoglycemia. CGM may also improve the care of intensive care unit patients treated with intensive insulin therapy and the large numbers of diabetic patients in general hospital wards.
Diabetes Self-Management Care via Cell Phone: A Systematic Review
Authors: Krishna Santosh , Boren Suzanne Austin
Published: January 2014

Background:

The objective of this study was to evaluate the evidence on the impact of cell phone interventions for persons with diabetes and/or obesity in improving health outcomes and/or processes of care for persons with diabetes and/or obesity.

Methods:

We searched Medline (1966–2007) and reviewed reference lists from included studies and relevant reviews to identify additional studies. We extracted descriptions of the study design, sample size, patient age, duration of study, technology, educational content and delivery environment, intervention and control groups, process and outcome measures, and statistical significance.

Results:

In this review, we included 20 articles, representing 18 studies, evaluating the use of a cell phone for health information for persons with diabetes or obesity. Thirteen of 18 studies measured health outcomes and the remaining 5 studies evaluated processes of care. Outcomes were grouped into learning, behavior change, clinical improvement, and improved health status. Nine out of 10 studies that measured hemoglobin A1c reported significant improvement among those receiving education and care support. Cell phone and text message interventions increased patient—provider and parent—child communication and satisfaction with care.

Conclusions:

Providing care and support with cell phones and text message interventions can improve clinically relevant diabetes-related health outcomes by increasing knowledge and self-efficacy to carry out self-management behaviors.
Skin Advanced Glycation End Product Accumulation is Poorly Reflected by Glycemic Control in Type 2 Diabetic Patients (ZODIAC-9)
Authors: Gerrits Esther G. , Lutgers Helen L. , Kleefstra Nanne , Groenier Klaas H. , Smit Andries J. , Gans Rijk O. B. , Bilo Henk J. G.
Published: January 2014

Background:

Glycemic memory can be reflected by tissue accumulation of advanced glycation end products (AGEs). In type 1 diabetes mellitus (T1DM) patients, hemoglobin A1c (HbA1c) levels over various time periods poorly predicted the accumulation of different AGEs in skin biopsies. Our aim was to investigate whether HbA1c assessments can predict the change in skin AGEs during time in type 2 diabetes mellitus (T2DM).

Methods:

We included 452 T2DM patients participating in a shared-care setting, who are screened annually for HbA1c and diabetic complications. Baseline and follow-up levels of skin AGEs were assessed with a validated noninvasive autofluorescence (AF) method, which is based on the fluorescence characteristics of certain AGEs.

Results:

Our study population had a mean age of 65 years and 54% were female. After a mean follow-up duration of 3.3 years, linear regression analyses showed weak relationships among different assessments of HbA1c (baseline, maximum, mean, and variance of HbA1c) and skin AF at follow-up. Baseline skin AF and age were predictors of skin AF at follow-up, but diabetes duration, smoking, and creatinine were of less or no predictive value for skin AF at follow-up.

Conclusions:

In our T2DM population, integrated HbA1c assessments over years poorly predict the change in skin AGE level measured by skin AF. These findings agree with results in patients with T1DM. This suggests either the need for longer exposure to glucose disturbances to change tissue AGEs or other mechanisms, such as oxidative stress, leading to AGE accumulation.
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.
A Look at the Current Reimbursement Environment for Continuous Glucose Monitoring (CGM): Understanding the Fundamentals
Authors: Telgener Patty Curoe , Lowe Serena
Published: January 2014

As reimbursement continues to decline for diabetes management technologies and practice overhead continues to rise, it is becoming increasingly important to understand the current reimbursement environment for new technological innovations in diabetes care. The current environment demands a strong partnership among providers, key stakeholder groups, and industry to advocate for favorable coding, coverage, and payment of these new advancements, in order to improve accessibility to the patient. This article describes trends in the current reimbursement environment for continuous glucose monitoring and provides recommendations on how to maneuver through the intricacies of coding and coverage related to this emerging category of glucose monitoring.