bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Glucose Testing in the Hospital: Error Sources and Risk Management
Authors: Nichols James H.
Published: January 2014

Glucose testing in the hospital with point-of-care devices presents multiple opportunities for error. Any device can fail under the right conditions. For glucose monitoring in the hospital, with thousands of operators, hundreds of devices, and dozens of locations involved, there is ample opportunity for errors that can impact the quality of test results. Errors can occur in any phase of the testing process: Preanalytic, analytic, or postanalytic. Common sources of meter error include patient or methodology interferences, operator mistakes, environmental exposure, and device malfunction. Early models of glucose meters had few internal checks or capability to warn the operator of meter problems. The latest generation of glucose monitors has a number of internal checks and controls engineered into the testing process to prevent serious errors or warn the operator by suppressing test results. Some of these control processes are built into the software and data management system of the meters, others require the hospital to do something, such as regularly clean the meter or analyze control samples of known glucose concentration, to verify meter performance. Hospitals need to be aware of the potential for errors by understanding weaknesses in the testing process that could lead to erroneous results and take steps to prevent errors from occurring or to minimize the harm to patients when errors do occur. The reliability of a glucose result will depend on the balance of internal control features available from manufacturers in conjunction with the liquid control analysis and other control processes (operator training, device validation, and maintenance) utilized by the hospitals.
Integration of Remote Blood Glucose Meter Upload Technology into a Clinical Pharmacist Medication Therapy Management Service
Authors: Schenk Robert J. , Schenk Jenna
Published: January 2014

A pharmacist-delivered, outpatient-focused medication therapy management (MTM) program is using a remote blood glucose (BG) meter upload device to provide better care and to improve outcomes for its patients with diabetes. Sharing uploaded BG meter data, presented in easily comprehensible graphs and charts, enables patients, caregivers, and the medical team to better understand how the patients' diabetes care is progressing.

Pharmacists are becoming increasingly more active in helping to manage patients' complex medication regimens in an effort to help detect and avoid medication-related problems. Working together with patients and their physicians as part of an interdisciplinary health care team, pharmacists are helping to improve medication outcomes. This article focuses on two case studies highlighting the Diabetes Monitoring Program, one component of the Meridian Pharmacology Institute MTM service, and discusses the clinical application of a unique BG meter upload device.
Diabetes and Biomarkers
Authors: Caveney Erica J. , Cohen Oren J.
Published: January 2014

Biomarkers play an integral part in conducting clinical trials and treating patients. In most instances, they help medical practitioners, researchers, and regulatory officials make well-informed, scientifically sound decisions. However, in clinical studies, there is often uncertainty in how much weight to place on biomarker results versus clinical outcomes. This uncertainty emanates from opposing goals of the drug approval process. On one hand, the process must ensure that all therapeutics tested are safe and that the benefits outweigh the risks. On the other hand, the process should allow therapies to be accessible to patients as quickly as reasonably possible. Judicious use of biomarkers in the drug development process can bring these goals into alignment. More efficient discovery and use of biomarkers in the development of antidiabetes drugs will depend on advancing our understanding of the pathogenesis of diabetes and especially its macrovascular complications.
Behavioral Science in Video Games for Children's Diet and Physical Activity Change: Key Research Needs
Authors: Baranowski Tom , Baranowski Janice , Thompson Debbe , Buday Richard
Published: January 2014

Innovative intervention programs are needed to overcome the limitations in previous programs that promoted change in diabetes risk behaviors in children. Serious video games show promise of changing dietary and physical activity behaviors, but research is needed on the optimal design of behavior-change procedures in video games, the mechanisms that account for changes obtained, and the groups in which these interventions work best. Such research will permit the optimal design of serious video games for diabetes and obesity prevention in the future.
Learning in a Virtual Environment Using Haptic Systems for Movement Re-Education: Can This Medium Be Used for Remodeling other Behaviors and Actions?
Authors: Merians Alma S. , Fluet Gerard G. , Qiu Qinyin , Lafond Ian , Adamovich Sergei V.
Published: January 2014

Robotic systems that are interfaced with virtual reality gaming and task simulations are increasingly being developed to provide repetitive intensive practice to promote increased compliance and facilitate better outcomes in rehabilitation post-stroke. A major development in the use of virtual environments (VEs) has been to incorporate tactile information and interaction forces into what was previously an essentially visual experience. Robots of varying complexity are being interfaced with more traditional virtual presentations to provide haptic feedback that enriches the sensory experience and adds physical task parameters. This provides forces that produce biomechanical and neuromuscular interactions with the VE that approximate real-world movement more accurately than visual-only VEs, simulating the weight and force found in upper extremity tasks. The purpose of this article is to present an overview of several systems that are commercially available for ambulation training and for training movement of the upper extremity. We will also report on the system that we have developed (NJIT-RAVR system) that incorporates motivating and challenging haptic feedback effects into VE simulations to facilitate motor recovery of the upper extremity post-stroke. The NJIT-RAVR system trains both the upper arm and the hand. The robotic arm acts as an interface between the participants and the VEs, enabling multiplanar movements against gravity in a three-dimensional workspace. The ultimate question is whether this medium can provide a motivating, challenging, gaming experience with dramatically decreased physical difficulty levels, which would allow for participation by an obese person and facilitate greater adherence to exercise regimes.
New Directions in the Use of Virtual Reality for Food Shopping: Marketing and Education Perspectives
Authors: Ruppert Barb
Published: January 2014

Virtual reality is used in marketing research to shape food selection and purchase decisions. Could it be used to counteract the marketing of less-nutritious foods and teach healthier food selection? This article presents interviews with Raymond Burke, Ph.D., of Indiana University Bloomington, and Rachel Jones, M.P.H., of the University of Utah College of Health. Topics covered include new marketing research technologies, including virtual reality simulations; retailing and shopper behavior; and the use of virtual grocery stores to help students explore quality of diet and food/nutrient relationships. The interviewees discuss how the technologies they have developed fit into research and behavior change related to obesity and diabetes.
Analysis: Accuracy Performance of the Medtronic NexSensor for 6 Days in an Inpatient Setting Using Abdomen and Buttocks Insertion Sites
Authors: Glandt Mariela , Raz Itamar
Published: January 2014

In an article in this issue of Journal of Diabetes Science and Technology, Peoples and colleagues address the issue that, while continuous glucose sensors have been shown to improve hemoglobin A1c, they are still fraught with concerns regarding accuracy and flexibility in sensor placement. Their study aimed to evaluate whether NexSensor, an improved version of the already commercially available Sof-Sensor, can be used for 6 days instead of the 3 days approved for Sof-Sensor in the United States. Also, the article aims to compare the accuracy of wearing the sensor in the abdomen versus the buttocks, given that this offers more flexibility than the approved labeling for Sof-Sensor, which is only in the abdomen. The study demonstrated that NexSensor is both safe and accurate for 6 days at both insertion sites. There was no statistically significant difference between the sites. As far as improved accuracy, the authors find evidence in favor of NexSensor as compared to Sof-Sensor, although this evidence is preliminary and is not backed by statistical significance measures.
Design of a Decision Support System to Help Clinicians Manage Glycemia in Patients with Type 2 Diabetes Mellitus
Authors: Rodbard David , Vigersky Robert A.
Published: January 2014

Objective:

We sought to develop a computerized clinical decision support for clinicians treating patients with type 2 diabetes mellitus (T2DM).

Methods:

We designed, developed, and tested a computer-assisted decision support (CADS) system using statistical analyses of self-monitoring of blood glucose data, laboratory data, medical and medication history, and individualized hemoglobin A1c goals. A rule-based expert system generated recommendations for changes in therapy and accompanying explanations.

Results:

A clinical decision support system (CADS) was developed that considers 9 classes of medications and 69 regimens with combinations of up to 4 therapeutic agents. The preferred sequences of regimens can be customized. The program is integrated with a “comprehensive diabetes management system,” electronic medical record systems, and a method for uploading data from memory glucose meters via telephone without use of a computer or the Internet. The software provides a report to the clinician regarding the overall quality of glycemic control and identifies problems, e.g., hypoglycemia, hyperglycemia, glycemic variability, and insufficient data. The program can recommend continuation of current therapy, adjustment of dosages of current medications, or change of regimen and can provide explanations for its recommendations. If the user rejects the recommendations, the program will recommend alternative approaches. The CADS also provides access to Food and Drug Administration-approved prescribing information, guidelines from professional organizations, and selections from the general medical literature. The system has been extensively tested with real and synthetic data and is ready for evaluation in multicenter clinical trials.

Conclusion:

A clinical decision support system to assist with the management of patients with T2DM was designed, developed, tested, and found to perform well.
Perioperative Hyperglycemia and Postoperative Infection after Lower Limb Arthroplasty
Authors: Mraovic Boris , Suh Donghun , Jacovides Christina , Parvizi Javad
Published: January 2014

Background:

One of the most serious complications after major orthopedic surgery is deep wound or periprosthetic joint infection. Various risk factors for infection after hip and knee replacement surgery have been reported, including patients' comorbidities and surgical technique factors. We investigated whether hyperglycemia and diabetes mellitus (DM) are associated with infection that requires surgical intervention after total hip and knee arthroplasty.

Methods:

We reviewed our computerized database for elective primary total hip and knee arthroplasty from 2000 to 2008. Demographic information, past medical history of patients, perioperative biochemistry, and postoperative complications were reviewed. Patients were divided into two groups: Infected group (101 patients who had surgical intervention for infection at our institution within 2 years after primary surgery) and noninfected group (1847 patients with no intervention with a minimum of one year follow-up. The data were analyzed using t, chi-squared, and Fisher's exact tests.

Results:

There were significantly more diabetes patients in the infected group compared with the noninfected group (22% versus 9%, p < .001). Infected patients had significantly higher perioperative blood glucose (BG) values: Preoperative BG (112 ± 36 versus 105 ± 31 mg/dl, p = .043) and postoperative day (POD) 1 BG (154 ± 37 versus 138 ± 31 mg/dl, p < .001). Postoperative morning hyperglycemia (BG >200 mg/dl) increased the risk for the infection more than two-fold. Non-DM patients were three times more likely to develop the infection if their morning BG was >140 mg/dl on POD 1, p = .001. Male gender, higher body mass index, knee arthroplasty, longer operative time and hospital stay, higher comorbidity index, history of myocardial infarction, congestive heart failure, and renal insufficiency were also associated with the infection.

Conclusions:

Diabetes mellitus and morning postoperative hyperglycemia were predictors for postoperative infection following total joint arthroplasty. Even patients without a diagnosis of DM who developed postoperative hyperglycemia had a significantly increased risk for the infection.
Food and Drug Administration Guidance: Supervisory Responsibilities of Investigators
Authors: Anderson Carl , Young Patti A. , Berenbaum Ann
Published: January 2014

Conducting clinical trials for diabetes can present researchers with a number of regulatory questions. The Food and Drug Administration (FDA) has increased regulatory enforcement at clinical sites, with an increased emphasis on oversight by principal investigators (PIs; referred to by the FDA as the clinical investigator). The FDA has issued a guidance document, “Guidance for Industry: Investigator Responsibilities— Protecting the Rights, Safety, and Welfare of Study Subjects” (2009), to assist investigators and sponsors. This guidance document breaks new ground regarding the FDA's expectations for investigator oversight of subinvestigators and study staff. The guidance document corresponds with a sharp increase in FDA warning letters to PIs for noncompliance with good clinical practice regulatory requirements. For the first time, an FDA guidance document discusses issues such as the delegation of authority, standard operating procedures, and training of study staff. The FDA provides specific examples with particular emphasis given to appropriate delegation of duties by the PI and ensuring that the clinical staff entrusted to carry out the trial has had adequate training and experience in order to allow them to perform the designated tasks.
The Association between Driving Distance and Glycemic Control in Rural Areas
Authors: Zgibor Janice C. , Gieraltowski Laura B. , Talbott Evelyn O. , Fabio Anthony , Sharma Ravi K. , Karimi Hassan
Published: January 2014

Background:

In order to optimize care and improve outcomes in people with diabetes, adequate access to health care facilities and resources for self-management is required.

Methods:

Data on 3369 individuals with type 2 diabetes who received education at 7 diabetes centers were collected prospectively between June 2005 and January 2007. The driving distances of subjects who were in good control [hemoglobin A1c (A1C) >7.0%] were compared with the driving distances of those who were not (A1C >7.0%). The association between A1C and improvement in A1C with travel burden was tested.

Results:

The mean distance subjects traveled to visit their center was 13.3 miles. The results indicated that residing more than 10 miles from the diabetes management center [odds ratio (OR) = 1.91, p < .0001], being younger (OR = 0.99, p = .00015), and having a longer duration of diabetes (OR = 1.03, p = .0007) were significant contributors to a A1C >7% adjusted for individual- and community-level factors. In addition, those who lived within 10 miles of their center were 2.5 times more likely to have improved their A1C values between their first and last Office visits.

Conclusion:

Health care providers should be aware of travel burden as a potential barrier to glycemic control. In the future, it may be useful to minimize driving distance for individuals with diabetes, perhaps by improved public transportation, more diabetes center locations in rural areas, telemedicine, or home visits.
Disease Registries on the Nationwide Health Information Network
Authors: Russler Daniel
Published: January 2014

Background:

Donation by individuals of their protected health information (PHI) for evidence-based research potentially benefits all individuals with disease through improved understandings of disease patterns. In the future, a better understanding of how disease features combine into unique patterns of disease will generate new disease classifications, supporting greater specificity in health management techniques. However, without large numbers of people who donate their PHI to disease registries designed for research, it is difficult for researchers to discover the existence of complex patterns or to create more specific evidence-based management techniques. In order to identify new opportunities in disease registry design, an analysis of the current stage of maturity of the newly created U.S. Nationwide Health Information Network (NwHIN) related to large-scale consumer donation of PHI is presented.

Methods:

Utilizing a use-case analysis methodology, the consumer-centric designs of the policies and technologies created for the NwHIN were examined for the potential to support consumer donations of PHI to research.

Results:

The NwHIN design has placed the enforcement point for the policy-based release of PHI over the Internet into a specialized gateway accessible to consumer authorization. However, current NwHIN policies leave the final decision regarding release of PHI for research to the health care providers rather than to the consumers themselves.

Conclusions:

Should disease registries designed for research be established on the NwHIN, consumers might then directly authorize the donation of their PHI to these disease registries. However, under current NwHIN policies, consumer authorization does not guarantee release of PHI by health providers.
Use of a Large Diabetes Electronic Medical Record System in India: Clinical and Research Applications
Authors: Pradeepa Rajendra , Prabu Anbalagan Viknesh , Jebarani Saravanan , Subhashini Sivasankaran , Mohan Viswanathan
Published: January 2014

Background:

The diabetes electronic medical record (DEMR) has emerged as an effective information management tool with the potential to improve diabetes care and research. This study reports on the usefulness of the DEMR system at Dr. Mohan's Diabetes Specialities Centre (DMDSC), Chennai, India, for clinical and research purposes.

Methods:

The DEMR, set up in 1996 at DMDSC, connects data of nine centers/clinics in different geographical areas in Southern India. The present data analysis is based on a total of 226,228 patients registered in the DEMR system at DMDSC between the years 1991 and 2010.

Results:

The DEMR included data of 139,906 male and 86,322 female patients, of whom 92.6% had type 2 diabetes mellitus (T2DM), 1.4% had type 1 diabetes mellitus (T1DM), and the rest had other types. Patients with T2DM had higher prevalence rates of neuropathy (33.1% vs 13.0%, p < .001), microalbuminuria (25.5% vs 20.0%, p < .001), coronary artery disease (17.5% vs 9.2%, p < .001) and peripheral vascular disease (3.9% vs 2.8%, p = .017) compared with T1DM patients, while prevalence of diabetic retinopathy was similar (37.9% vs 35.7%, p = .06). Prevalence of microvascular and macrovascular complications of diabetes increased with increasing glycated hemoglobin levels ( p for trend < .001) and increasing diabetes duration ( p for trend < .001).

Conclusions:

The DEMR helps track diabetes care and is a valuable tool for research.
Metabolic Biofouling of Glucose Sensors in Vivo: Role of Tissue Microhemorrhages
Authors: Klueh Ulrike , Liu Zenghe , Feldman Ben , Henning Timothy P. , Cho Brian , Ouyang Tianmei , Kreutzer Don
Published: January 2014

Objective:

Based on our in vitro study that demonstrated the adverse effects of blood clots on glucose sensor function, we hypothesized that in vivo local tissue hemorrhages, induced as a consequence of sensor implantation or sensor movement post-implantation, are responsible for unreliable readings or an unexplained loss of functionality shortly after implantation.

Research Design and Methods:

To investigate this issue, we utilized real-time continuous monitoring of blood glucose levels in a mouse model. Direct injection of blood at the tissue site of sensor implantation was utilized to mimic sensor-induced local tissue hemorrhages.

Results:

It was found that blood injections, proximal to the sensor, consistently caused lowered sensor glucose readings, designated temporary signal reduction, in vivo in our mouse model, while injections of plasma or saline did not have this effect.

Conclusion:

These results support our hypothesis that tissue hemorrhage and resulting blood clots near the sensor can result in lowered local blood glucose concentrations due to metabolism of glucose by the clot. The lowered local blood glucose concentration led to low glucose readings from the still functioning sensor that did not reflect the systemic glucose level.
Biomechanics of the Sensor-Tissue Interface—Effects of Motion, Pressure, and Design on Sensor Performance and Foreign Body Response—Part II: Examples and Application
Authors: Helton Kristen L. , Ratner Buddy D. , Wisniewski Natalie A.
Published: January 2014

This article is the second part of a two-part review in which we explore the biomechanics of the sensor-tissue interface as an important aspect of continuous glucose sensor biocompatibility. Part I, featured in this issue of Journal of Diabetes Science and Technology, describes a theoretical framework of how biomechanical factors such as motion and pressure (typically micromotion and micropressure) affect tissue physiology around a sensor and in turn, impact sensor performance. Here in Part II, a literature review is presented that summarizes examples of motion or pressure affecting sensor performance. Data are presented that show how both acute and chronic forces can impact continuous glucose monitor signals. Also presented are potential strategies for countering the ill effects of motion and pressure on glucose sensors. Improved engineering and optimized chemical biocompatibility have advanced sensor design and function, but we believe that mechanical biocompatibility, a rarely considered factor, must also be optimized in order to achieve an accurate, long-term, implantable sensor.
The Effect of Real-Time Continuous Glucose Monitoring on Glycemic Control in Patients with Type 2 Diabetes Mellitus
Authors: Ehrhardt Nicole M. , Chellappa Mary , Walker M. Susan , Fonda Stephanie J. , Vigersky Robert A.
Published: January 2014

Background:

Real-time continuous glucose monitoring (RT-CGM) improves hemoglobin A1c (A1C) and hypoglycemia in people with type 1 diabetes mellitus and those with type 2 diabetes mellitus (T2DM) on prandial insulin; however, it has not been tested in people with T2DM not taking prandial insulin. We evaluated the utility of RT-CGM in people with T2DM on a variety of treatment modalities except prandial insulin.

Methods:

We conducted a prospective, 52-week, two-arm, randomized trial comparing RT-CGM ( n = 50) versus self-monitoring of blood glucose (SMBG) ( n = 50) in people with T2DM not taking prandial insulin. Real-time continuous glucose monitoring was used for four 2-week cycles (2 weeks on/1 week off). All patients were managed by their usual provider. This article reports on changes in A1C 0–12 weeks.

Results:

Mean (±standard deviation) decline in A1C at 12 weeks was 1.0% (±1.1%) in the RT-CGM group and 0.5% (±0.8%) in the SMBG group ( p = .006). There were no group differences in the net change in number or dosage of hypoglycemic medications. Those who used the RT-CGM for ±48 days (per protocol) reduced their A1C by 1.2% (±1.1%) versus 0.6% (±1.1%) in those who used it <48 days ( p = .003). Multiple regression analyses statistically adjusting for baseline A1C, an indicator for usage, and known confounders confirmed the observed differences between treatment groups were robust ( p = .009). There was no improvement in weight or blood pressure.

Conclusions:

Real-time continuous glucose monitoring significantly improves A1C compared with SMBG in patients with T2DM not taking prandial insulin. This technology might benefit a wider population of people with diabetes than previously thought.
Use of a Novel Fluorescent Glucose Sensor in Volunteer Subjects with Type 1 Diabetes Mellitus
Authors: Peyser Thomas , Zisser Howard , Khan Uzma , Jovanovic Lois , Bevier Wendy , Romey Matt , Suri Jeff , Strasma Paul , Tiaden Stephanie , Gamsey Soya
Published: January 2014

Background:

Stress hyperglycemia in the critically ill has been found to be associated with increased morbidity and mortality. Studies have found significant improvements in morbidity and mortality in postsurgical patients whose glucose levels were closely maintained in the euglycemic range. However, subsequent studies, in particular the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study, found no improvement in subjects with tight glycemic control. In addition to differences in protocol design, patients in the tight glycemic control arm of the NICE-SUGAR study experienced high rates of hypoglycemia compared with other studies. One interpretation of the NICE-SUGAR study results is that it is difficult to achieve normal glycemia in critically ill patients with existing glucose monitoring technology. The purpose of the study reported here was to evaluate the safety and performance of a continuous intravascular glucose sensor that could be used in the future in critically ill patients.

Methods:

A first-generation prototype of an intravascular continuous glucose sensor was evaluated in 29 volunteer subjects with type 1 diabetes mellitus. The sensor operates on the principle of quenched fluorescence. The fluorescent emission from the sensor chemistry is nonlinear, resulting in improved accuracy in the hypoglycemic range. The duration of each study was 8 hours. Sensor output was compared with temporally correlated reference measurements made from venous samples on a laboratory glucose analyzer.

Results:

Data were obtained from 18 of the 29 subjects in the study. Data were analyzed retrospectively using a factory calibration plus a one-point in vivo calibration. The mean absolute relative difference was 7.97%, and 95.1% of all the points were in zone A of the Clarke error grid.

Conclusions:

This pilot study was the first use in human subjects of a prototype of the GluCath Intravascular Continuous Glucose Monitoring System (GluCath System). The GluCath System is based on a novel fluorescent sensor chemistry. The study found the GluCath System had a high level of accuracy as compared with a laboratory reference analyzer.
Patient Understanding of Diabetes Self-Management: Participatory Decision-Making in Diabetes Care
Authors: Quinn Charlene C. , Royak-Schaler Renee , Lender Dan , Steinle Nanette , Gadalla Shahinaz , Zhan Min
Published: January 2014

Objective:

Our aim was to determine whether patient participation in decision-making about diabetes care is associated with understanding of diabetes self-management and subsequent self-care practices. We also identified issues that would impact messaging for use in mobile diabetes communication.

Research Design and Methods:

A cross-sectional observational study was conducted with type 2 diabetes patients ( n = 81) receiving their care at the University of Maryland Joslin Diabetes Center. A convenience sample of patients were eligible to participate if they were aged 25–85 years, had type 2 diabetes, spoke English, and visited their physician diabetes manager within the past 6 months. In-person patient interviews were conducted at the time of clinic visits to assess patient understanding of diabetes management, self-care practices, and perceptions of participation in decision-making about diabetes care.

Results:

African Americans reported fewer opportunities to participate in decision-making than Caucasians, after controlling for education [mean difference (MD) = −2.4, p = .02]. This association became insignificant After controlling for patient-physician race concordance (MD = −1.5, p = .21). Patient understanding of self-care was predicted by having greater than high school education (MD = 3.6, p = .001) and having physicians who involved them in decision-making about their care. For each unit increase in understanding of diabetes self-care, the mean patient self-care practice score increased by 0.16 ( p = .003), after adjustment for patient race and education.

Conclusions:

Patient participation in decision-making is associated with better understanding of care. Participation in decision-making plays a key role in patient understanding of diabetes self-management and subsequent self-care practices. Patients with limited education need specific instruction in foot care, food choices, and monitoring hemoglobin A1c.
Intensive Insulin Therapy in Critically Ill Hospitalized Patients: Making it Safe and Effective
Authors: Klonoff David C.
Published: January 2014

Intensive insulin therapy (IIT) for hyperglycemia in critically ill patients has become a standard practice. Target levels for glycemia have fluctuated since 2000, as evidence initially indicated that tight glycemic control to so-called normoglycemia (80–110 mg/dl) leads to the lowest morbidity and mortality without hypoglycemic complications. Subsequent studies have demonstrated minimal clinical benefit combined with greater hypoglycemic morbidity and mortality with tight glycemic control in this population. The consensus glycemic targets were then liberalized to the mid 100s (mg/dl).

Handheld POC blood glucose (BG) monitors have migrated from the outpatient setting to the hospital environment because they save time and money for managing critically ill patients who require IIT. These devices are less accurate than hospital-grade POC blood analyzers or central laboratory analyzers.

Three questions must be answered to understand the role of IIT for defined populations of critically ill patients: (1) How safe is IIT, with various glycemic targets, from the risk of hypoglycemia? (2) How tightly must BG be controlled for this approach to be effective? (3) What role does the accuracy of BG measurements play in affecting the safety of this method? For each state of impaired glucose regulation seen in the hospital, such as hyperglycemia, hypoglycemia, or glucose variability, the benefits, risks, and goals of treatment, including IIT, might differ.

With improved accuracy of BG monitors, IIT might be rendered even more intensive than at present, because patients will be less likely to receive inadvertent overdosages of insulin. Greater doses of insulin, but with dosing based on more accurate glucose levels, might result in less hypoglycemia, less hyperglycemia, and less glycemic variability.
Innovations in Technology for the Treatment of Diabetes: Clinical Development of the Artificial Pancreas (an Autonomous System)
Authors: Klonoff David C. , Zimliki Charles L. , Stevens LCDR Alan , Beaston Patricia , Pinkos Arleen , Choe Sally Y. , Arreaza-Rubín Guillermo , Heetderks William
Published: January 2014

The Food and Drug Administration in collaboration with the National Institutes of Health presented a public workshop to facilitate medical device innovation in the development of the artificial pancreas (or autonomous system) for the treatment of diabetes mellitus on November 10, 2010 in Gaithersburg, Maryland.

The purpose of the workshop was to discuss four aspects of artificial pancreas research and development, including: (1) the current state of device systems for autonomous systems for the treatment of diabetes mellitus; (2) challenges in developing this expert device system using existing technology; (3) clinical expectations for these systems; and (4) development plans for the transition of this device system toward an outpatient setting.

The patients discussed how clinical science, system components, and regulatory policies will all need to harmonize in order to achieve the goal of seeing an AP product brought forward to the marketplace for patients to use.
Evaluation of a Novel Continuous Glucose Measurement Device in Patients with Diabetes Mellitus across the Glycemic Range
Authors: Morrow Linda , Hompesch Marcus , Tideman Ann M. , Matson Jennifer , Dunne Nancy , Pardo Scott , Parkes Joan L. , Schachner Holly C. , Simmons David A.
Published: January 2014

Background:

This glucose clamp study assessed the performance of an electrochemical continuous glucose monitoring (CGM) system for monitoring levels of interstitial glucose. This novel system does not require use of a trocar or needle for sensor insertion.

Method:

Continuous glucose monitoring sensors were inserted subcutaneously into the abdominal tissue of 14 adults with type 1 or type 2 diabetes. Subjects underwent an automated glucose clamp procedure with four consecutive post-steady-state glucose plateau periods (40 min each): (a) hypoglycemic (50 mg/dl) (b) hyperglycemic (250 mg/dl), (c) second hypoglycemic (50 mg/dl), and (d) euglycemic (90 mg/dl). Plasma glucose results obtained with YSI glucose analyzers were used for sensor calibration. Accuracy was assessed retrospectively for plateau periods and transition states, when glucose levels were changing rapidly (approximately 2 mg/dl/min).

Results:

Mean absolute percent difference (APD) was lowest during hypoglycemic plateaus (11.68%, 14.15%) and the euglycemic-to-hypoglycemic transition (14.21%). Mean APD during the hyperglycemic plateau was 17.11%; mean APDs were 18.12% and 19.25% during the hypoglycemic-to-hyperglycemic and hyperglycemic-to-hypoglycemic transitions, respectively. Parkes (consensus) error grid analysis (EGA) and rate EGA of the plateaus and transition periods, respectively, yielded 86.8% and 68.6% accurate results (zone A) and 12.1% and 20.0% benign errors (zone B). Continuous EGA yielded 88.5%, 75.4%, and 79.3% accurate results and 8.3%, 14.3%, and 2.4% benign errors for the euglycemic, hyperglycemic, and hypoglycemic transition periods, respectively. Adverse events were mild and unlikely to be device related.

Conclusion:

This novel CGM system was safe and accurate across the clinically relevant glucose range.
Real-Life Utilization of Real-Time Continuous Glucose Monitoring: The Complete Picture
Authors: Ramchandani Neesha , Arya Sandeep , Ten Svetlana , Bhandari Sonal
Published: January 2014

Background:

Very few studies to date have analyzed the reasons why some people do not use real-time continuous glucose monitoring (RT-CGM) continuously, especially given its positive glycemic outcomes, or choose not to wear it at all, even after learning about its benefits.

Methods:

A questionnaire was designed to assess real-life use of and issues surrounding RT-CGM. Hemoglobin A1c (HbA1c) and duration of sensor use were also obtained from the patients' charts.

Results:

Fifty-eight subjects with type 1 diabetes (T1DM), average age 15.0 ± 4.8 years, T1DM duration 5.7 ± 3.8 years, HbA1c 8.8 ± 2.1%, 50% with RT-CGM, were included in the analysis. Hemoglobin A1c was lower with increased RT-CGM use. Real-time continuous glucose monitoring was ordered to improve control. Users liked the continuous data. The most disliked part was pain and discomfort. Occasional users described RT-CGM as annoying, a hassle, and interfering with their lives. Reasons for discontinuing RT-CGM included problematic equipment and inaccuracy (64%), intrusion in life (36%), and insurance issues (29%). Twenty-one percent of nonusers reported RT-CGM to be inconvenient or a hassle or just did not want it. Fifty-two percent of subjects continue to use RT-CGM despite reported problems.

Conclusion:

Real-time continuous glucose monitoring is a beneficial tool for improving glycemic control, and many use it despite reported problems and hassles with current devices. However, this technology has not been wholeheartedly embraced by many individuals with T1DM, especially in youngsters, because of issues mentioned here. Based on the findings of this study, it is hoped that improvements will be made to RT-CGM technology so that more people with diabetes will embrace this beneficial tool.
A 16-Week Open-Label, Multicenter Pilot Study Assessing Insulin Pump Therapy in Patients with Type 2 Diabetes Suboptimally Controlled with Multiple Daily Injections
Authors: Frias Juan P. , Bode Bruce W. , Bailey Timothy S. , Kipnes Mark S. , Brunelle Rocco , Edelman Steven V.
Published: January 2014

Background:

We assessed the efficacy, safety, and patient-reported outcomes (PROs) of insulin pump therapy in patients with type 2 diabetes mellitus (T2DM) who were suboptimally controlled with a multiple daily injection (MDI) regimen.

Methods:

In this subanalysis of a 16-week multicenter study, 21 insulin-pump-naïve patients [age 57 ± 13 years, hemoglobin A1c (A1C) 8.4 ± 1.0%, body weight 98 ± 20 kg, total daily insulin dose 99 ± 65 U, mean ± standard deviation] treated at baseline with MDI therapy with or without oral antidiabetic agents discontinued all diabetes medications except metformin and initiated insulin pump therapy. Insulin was titrated to achieve the best possible glycemic control with the simplest possible dosing regimen. Outcome measures included A1C, fasting and postprandial glucose, body weight, incidence of hypoglycemia, and PROs.

Results:

Glycemic control improved significantly after 16 weeks: A1C 7.3 ± 1.0% (−1.1 ± 1.2%, p < .001), fasting glucose 133 ± 33mg/dl (−32 ± 74 mg/dl, p < .005), and postprandial glucose 153 ± 35 mg/dl (−38 ± 46 mg/dl, p < .001). At week 16, the mean daily basal, bolus, and total insulin doses were 66 ± 36, 56 ± 40, and 122 ± 72 U (1.2 U/kg), respectively, and 90% of patients were treated with two or fewer daily basal rates. Body weight increased by 2.8 ± 2.6 kg ( p < .001). Mild hypoglycemia was experienced by 81% of patients at least once during the course of the study with no episodes of severe hypoglycemia. There were significant improvements in PRO measures.

Conclusions:

Insulin pump therapy using a relatively simple dosing regimen safely improved glucose control and PROs in patients with T2DM who were unable to achieve glycemic targets with MDI therapy. Controlled trials are needed to further assess the clinical benefits and cost-effectiveness of insulin pumps in this patient population.
A Stepwise Approach toward Closed-Loop Blood Glucose Control for Intensive Care Unit Patients: Results from a Feasibility Study in Type 1 Diabetic Subjects Using Vascular Microdialysis with Infrared Spectrometry and a Model Predictive Control Algorithm
Authors: Feichtner Franz , Mader Julia K. , Schaller Roland , Schaupp Lukas , Ellmerer Martin , Korsatko Stefan , Kondepati Venkata R. , Heise H. Michael , Wilinska Malgorzata E. , Hovorka Roman , Pieber Thomas R.
Published: January 2014

Background:

Glycemic control can reduce the mortality and morbidity of intensive care patients. The CLINICIP (closed-loop insulin infusion for critically ill patients) project aimed to develop a closed-loop control system for this patient group. Following a stepwise approach, we combined three independently tested subparts to form a semiautomatic closed-loop system and evaluated it with respect to safety and performance aspects by testing it in subjects with type 1 diabetes mellitus (T1DM) in a first feasibility trial.

Methods:

Vascular microdialysis, a multianalyte infrared spectroscopic glucose sensor, and a standard insulin infusion pump controlled by an adaptive model predictive control (MPC) algorithm were combined to form a closed-loop device, which was evaluated in four T1DM subjects during 30-hour feasibility studies. The aim was to maintain blood glucose concentration in the target range between 80 and 110 mg/dl.

Results:

Mean plasma glucose concentration was 110.5 ± 29.7 mg/dl. The MPC managed to establish normoglycemia within 105 ± 78 minutes after trial start and managed to maintain glucose concentration within the target range for 47% of the time. The hyperglycemic index averaged to 11.9 ± 5.3 mg/dl.

Conclusion:

Data of the feasibility trial illustrate the device being effective in controlling glycemia in T1DM subjects. However, the monitoring part of the loop must be improved with respect to accuracy and precision before testing the system in the target population.
Convergence of Prevalence Rates of Diabetes and Cardiometabolic Risk Factors in Middle and Low Income Groups in Urban India: 10-Year Follow-Up of the Chennai Urban Population Study
Authors: Deepa Mohan , Anjana Ranjit Mohan , Manjula Datta , Narayan K.M. Venkat , Mohan Viswanathan
Published: January 2014

Aim:

The aim of this study was to look for temporal changes in the prevalence of diabetes and cardiometabolic risk factors in two residential colonies in Chennai.

Methods:

Chennai Urban Population Study (CUPS) was carried out between 1996–1998 in Chennai in two residential colonies representing the middle income group (MIG) and lower income group (LIG), respectively. The MIG had twice the prevalence rate of diabetes as the LIG and higher prevalence rates of hypertension, obesity, and dyslipidemia. They were motivated to increase their physical activity, which led to the building of a park. The LIG was given standard lifestyle advice. Follow-up surveys of both colonies were performed after a period of 10 years.

Results:

In the MIG, the prevalence of diabetes increased from 12.4 to 15.4% (24% increase), while in the LIG, it increased from 6.5 to 15.3% (135% increase, p < .001). In the LIG, the prevalence rates of central obesity (baseline vs follow-up, male: 30.8 vs 50.9%, p < .001; female: 16.9 vs 49.8%, p < .001), hypertension (8.4 vs 20.1%, p < .001), hypercholesterolemia (14.2 vs. 20.4%, p < .05), and hypertriglyceridemia (8.0 vs 23.5%, p < .001) significantly increased and became similar to that seen in the MIG.

Conclusion:

There is a rapid reversal of socioeconomic gradient for diabetes and cardiometabolic risk factors in urban India with a convergence of prevalence rates among people in the MIG and LIG. This could have a serious economic impact on poor people in developing countries such as India.
Diabetes and Technology for Increased Activity (DaTA) Study: Results of a Remote Monitoring Intervention for Prevention of Metabolic Syndrome
Authors: Stuckey Melanie , Russell-Minda Elizabeth , Read Emily , Munoz Claudio , Shoemaker Kevin , Kleinstiver Peter , Petrella Robert
Published: January 2014

Objective:

An increasingly aged, overweight, and sedentary population has resulted in elevated risk of cardiovascular disease (CVD). The escalating incidence of diabetes and other chronic illnesses, deficits in health care budgets, and physician shortages, especially in rural communities, have prompted investigations of feasible solutions. The Diabetes and Technology for Increased Activity (DaTA) study was designed to test the effectiveness of a lifestyle intervention driven by self-monitoring of blood glucose (BG), blood pressure (BP), physical activity (PA), and weight to positively impact CVD risk factors in a medically underserviced rural population with a high incidence of metabolic syndrome (MS).

Research Design and Methods:

Conducted in a community-based research setting, this single-center open feasibility study used smart phones to transmit BP, BG, pedometer, weight, heart rate, and activity measurements to a database. Technology allowed participants to interface with the clinical team and self-monitor their personal health indicators.

Results:

Twenty-four participants aged 30 to 71 years completed the 8-week intervention. Participants had significant improvement in clinic ( p = .046) and self-monitored diastolic BP ( p = .001), body mass index ( p = .002), and total cholesterol ( p = .009), and steps per day. Daily PA increased as well as participants' interest in and willingness to make lifestyle changes that impact health outcomes.

Conclusions:

The DaTA study demonstrated that self-monitoring of the risk factors for MS and increased PA improved the participant's CVD risk profile. Considering the 8-week time period of this intervention, results are encouraging. This lifestyle intervention, which uses education and technology as tools, confirms the utility of remote health monitoring.
Effect of Pioglitazone and Ramipril on Biomarkers of Low-Grade Inflammation and Vascular Function in Nondiabetic Patients with Increased Cardiovascular Risk and an Activated Inflammation: Results from the PIOace Study
Authors: Pfützner Andreas , Hanefeld Markolf , Dekordi Lida A. , Müller Jürgen , Kleine Iris , Fuchs Winfried , Forst Thomas
Published: January 2014

Aims:

This study investigated the effects of pioglitazone (PIO), ramipril (RAM), or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive patients with increased cardiovascular risk.

Methods and Results:

Patients enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72 male, 77 female, aged 60 ± 9 years, body mass index 30.4 ± 4.7 kg/m2, duration of hypertension 9 ± 8 years) were treated with either 30/45 mg PIO (dose titration), 2.5/5 mg RAM, or their combination for 12 weeks. A reduction in high-sensitivity C-reactive protein was observed with PIO (−0.89 ± 1.98 mg/liter; −25%) and PIRA (−0.49 ± 2.11 mg/liter; −16%), while an increase was seen with RAM (0.58 ± 2.13 mg/liter; +20%, p < .05 vs PIO and PIRA). The 24-hour blood pressure profile showed a small increase with both monotherapies but a decrease with PIRA ( p < .05 vs PIO). Improvements in biomarkers of chronic systemic inflammation and insulin resistance (IR) were observed in the PIO and PIRA arms only [PIO/RAM/PIRA: homeostasis model of assessment of IR: −0.78 ± 1.39 (−29%)/0.15 ± 1.03 (+5%)/ −1.44 ± 2.83 (−40%); adiponectin: 8.51 ± 5.91 (+104%)/ 0.09 ± 2.63 (+1%)/ 8.86 ± 6.37 mg/liter (+107%); matrix metalloproteinase-9: −48 ± 127 (−12%)/−1 ± 224 (0%)/−60 ± 210 ng/ml (−13%), p < .05 for RAM vs PIO or PIRA in all cases].

Conclusions:

Our 3-month study in nondiabetic hypertensive patients showed a decrease in biomarkers of IR and chronic systemic inflammation with the PIO monotherapy and the PIRA combination only, which may help to explain some findings in other cardiovascular outcome trials.
Preanalytic and Analytic Accuracy: Toward More Realistic and Meaningful Self-Monitoring of Blood Glucose Submissions for Regulatory Approval
Authors: Cembrowski George S.
Published: January 2014

Dr. Cembrowski provides an analysis of an article by Harrison and colleagues in this issue of Journal of Diabetes Science and Technology in which the authors describe the evaluation of a new device for self-monitoring of blood glucose, the Bayer CONTOUR® blood glucose monitoring system.