bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Olibra: A 12-Week Randomized Controlled Trial and a Review of Earlier Studies
Authors: Rebello Candida J. , Martin Corby K. , Johnson William D. , O'Neil Carol E. , Greenway Frank L.
Published: January 2014

Background:

Intervention strategies that harness the body's appetite and satiety regulating signals provide a means of countering excessive energy intake.

Methods:

Eighty-two subjects were enrolled (18–60 years, body mass index: 25–40 kg/m2) in a randomized, placebo-controlled, double-blind, parallel trial. During a 12-week period, the effects of Olibra™ fat emulsion (2.1 g twice daily) on food intake, appetite, satiety, weight, and body composition were compared with those of a twice daily administered placebo (1.95 g milk fat). On days −7, 0, and 28, Olibra or the placebo added to 200 g of yogurt was served at breakfast and lunch. Food intake, appetite, and satiety were assessed after lunch and dinner. Body weight was measured on days −7, 0, 14, 28, 56, and 84. Body fat, waist circumference, and waist-hip ratio were determined on days 0 and 84. The Eating Inventory was administered at screening and on day 28. Data relating to 71 subjects were analyzed using analysis of covariance.

Results:

At 12 weeks, body weight was reduced in the test group (2.17 ± 0.46 kg standard error of the mean, p < .0001) and the control group (1.68 ± 0.42 kg, p < .0001). Waist circumference decreased by 2.93 ± 0.85 cm in the test group ( p = .001) and by 1.78 ± 0.74 cm in the control group ( p = .02). differential weight and waist circumference reductions were not significant. Hunger scores (Eating Inventory) decreased more in the test group ( p = .0082). differential group effects were not significant for body fat, waist-hip ratio, food intake, appetite, and satiety.

Conclusions:

At this dose, Olibra did not exert a consistent effect on food intake, appetite regulation, body weight, or body composition.
Undeniable Need for Ultrafast-Acting Insulin: The Pediatric Perspective
Authors: Cengiz Eda
Published: January 2014

Insulin therapy in youth with type 1 diabetes mellitus (T1DM) poses a special challenge because childhood is an unsteady state with increasing weight, height, and caloric needs, leading to varying insulin requirements. The current rapid-acting insulin analogs are not as fast and short-acting as needed to meet these challenges. This review describes the unique characteristics of insulin action in youth with T1DM based on previously published euglycemic clamp studies. It also explains the rationale behind the need for ultrafast-acting insulins to advance open- and closed-loop insulin therapy for the pediatric population with diabetes. Lastly, it briefly summarizes ongoing and future projects to accelerate insulin action in youth with T1DM.
Video Games for Diabetes Self-Management: Examples and Design Strategies
Authors: Lieberman Debra A.
Published: January 2014

The July 2012 issue of the Journal of Diabetes Science and Technology includes a special symposium called “Serious Games for Diabetes, Obesity, and Healthy Lifestyle.” As part of the symposium, this article focuses on health behavior change video games that are designed to improve and support players' diabetes self-management. Other symposium articles include one that recommends theory-based approaches to the design of health games and identifies areas in which additional research is needed, followed by five research articles presenting studies of the design and effectiveness of games and game technologies that require physical activity in order to play.

This article briefly describes 14 diabetes self-management video games, and, when available, cites research findings on their effectiveness. The games were found by searching the Health Games Research online searchable database, three bibliographic databases (ACM Digital Library, PubMed, and Social Sciences Databases of CSA Illumina), and the Google search engine, using the search terms “diabetes” and “game.” Games were selected if they addressed diabetes self-management skills.
Two-Player Partnered Exergame for Obesity Prevention: Using Discrepancy in Players' Abilities as a Strategy to Motivate Physical Activity
Authors: Feltz Deborah L. , Irwin Brandon , Kerr Norbert
Published: January 2014

Background:

Physical inactivity is associated with obesity and type 2 diabetes. A key obstacle to physical activity is lack of motivation. Although some interactive exercise games (i.e., exergames—video games that require physical exertion in order to play) motivate players to exercise more, few games take advantage of group dynamics to motivate players' duration of exercise. In a test of the Kohler motivation gain effect, this study varied the ability level of a virtually presented partner in an interactive exergame that focused on abdominal strength to identify effects on a subject's (S') persistence with the task.

Method:

Male ( n = 63) and female ( n = 72) undergraduate students were randomly assigned to one of four conditions (individual control or low-, moderate-, or high- partner discrepancy) in a conditions x gender factorial design and tested on a series of isometric abdominal exercises using PlayStation 2 EyeToy: Kinetic software. They performed the first series of five exercises alone (trial block 1), and after a rest period, those in the partner conditions performed remaining trials (trial block 2) with a same-sex virtually presented partner whom they could observe during their performance, while those in the individual control condition performed the remaining trials alone. In the partner conditions, the partner's performance was manipulated to be always better than the S's, the exact difference depending on the discrepancy condition. The partnered tasks were conjunctive; that is, success in the game depended on the performance of the weaker team member. Persistence, the outcome measure for this study, consisted of the total number of seconds the S held the exercise position.

Results:

Using planned orthogonal contrasts on difference scores between blocks 1 and 2, results showed that persistence was significantly ( p < .001) greater in all experimental conditions with a virtually presented partner ( M = 33.59 s) than in the individual control condition ( M = −49.04 s). Subjects demonstrated more persistence in the moderate-discrepancy condition ( M = 51.36 s) than in the low-discrepancy condition ( M = 22.52 s) or the high-discrepancy condition ( M = 26.89 s). A significant quadratic trend confirmed the expected inverted-U function relating partner discrepancy and persistence ( p = .025). Although Ss persisted longer and had higher heart rate in partnered conditions, they did not perceive their exertion to be any higher than those in the individual condition.

Conclusions:

Virtually presented partners who are moderately more capable than participants are the most effective at improving persistence in exergame tasks.
Using an Alternate Reality Game to Increase Physical Activity and Decrease Obesity Risk of College Students
Authors: Johnston Jeanne D. , Massey Anne P. , Marker-Hoffman Rickie Lee
Published: January 2014

Background:

This quasi-experimental study investigated a game intervention—specifically, an alternate reality game (ARG)—as a means to influence college students' physical activity (PA). An ARG is an interactive narrative that takes place in the real world and uses multiple media to reveal a story.

Method:

Three sections of a college health course ( n = 115 freshman students) were assigned either to a game group that played the ARG or to a comparison group that learned how to use exercise equipment in weekly laboratory sessions. Pre- and post-intervention measures included weight, waist circumference, body mass index (BMI), percentage body fat (PBF), and self-reported moderate physical activity (MPA) and vigorous physical activity (VPA), and PA (steps/week).

Results:

A significant group x time interaction ( p = .001) was detected for PA, with a significant increase in PA for the game ( p < .001) versus a significant decrease ( p = .001) for the comparison group. Significant within-group increases for weight ( p = .001), BMI ( p = .001), and PBF ( p = .001) were detected. A significant group x time interaction ( p = .001) was detected when analyzing self-reported VPA, with both groups reporting decreases in VPA over time; however, the decrease was only significant for the comparison group ( p < .001). No significant group differences were found for MPA.

Conclusions:

It is important that any intervention meet the needs and interests of its target population. Here, the ARG was designed in light of the learning preferences of today's college students—collaborative and social, experiential and media-rich. Our results provide preliminary evidence that a game intervention can positively influence PA within the college student population.
Novel Approaches to Obesity Prevention: Effects of Game Enjoyment and Game Type on Energy Expenditure in Active Video Games
Authors: Lyons Elizabeth J. , Tate Deborah F. , Komoski Stephanie E. , Carr Philip M. , Ward Dianne S.
Published: January 2014

Background:

Some active video games have been found to promote physical activity adherence because of enjoyment. However, many active games are exercise themed, which may interfere with the distracting properties that make game-based exercise more enjoyable than traditional exercise. This study compared exercise-themed and game-themed active games to investigate differences in energy expenditure and enjoyment.

Method:

Young adults ( N = 100, 50 female, 55 overweight, aged 18–35 years) played two of four Wii Fit games (one aerobic game and one balance game per person) for 10 min each. Of the two aerobic games, one was exercise themed (jogging) and the other was game themed (hula hooping). Both balance games were game themed. Energy expenditure and enjoyment were measured.

Results:

After adjustment for gender and weight, aerobic games produced 2.70 kcal/kg−1/h−1 (95% confidence interval 2.41, 3.00) greater energy expenditure than balance games ( p < .001), but balance games were more enjoyable ( p < .001). In aerobic games, jogging produced greater energy expenditure than hula hooping in normal-weight and male participants ( p < .001); in overweight and female participants, no differences were found ( p > .17). Hula hooping was enjoyed more than jogging ( p = .008). Enjoyment predicted energy expenditure in aerobic games ( B = 0.767, p = .010).

Conclusions:

Aerobic games produced greater energy expenditure but lower enjoyment than balance games, and a game-themed aerobic game was found more enjoyable than an exercise-themed aerobic game. Integrating more strenuous activity into entertaining games instead of games that simply simulate exercise may be a fruitful avenue for active game development.
Increased Risk of Acute Hepatitis B among Adults with Diagnosed Diabetes Mellitus
Authors: Reilly Meredith L. , Schillie Sarah F. , Smith Emily , Poissant Tasha , Vonderwahl Candace W. , Gerard Kristin , Baumgartner Jennifer , Mercedes Lynne , Sweet Kristin , Muleta Daniel , Zaccaro Daniel J. , Klevens R. Monina , Murphy Trudy V.
Published: January 2014

Introduction:

The risk of acute hepatitis B among adults with diabetes mellitus is unknown. We investigated the association between diagnosed diabetes and acute hepatitis B.

Methods:

Confirmed acute hepatitis B cases were reported in 2009–2010 to eight Emerging Infections Program (EIP) sites; diagnosed diabetes status was determined. Behavioral Risk Factor Surveillance System respondents residing in EIP sites comprised the comparison group. Odds ratios (ORs) comparing acute hepatitis B among adults with diagnosed diabetes versus without diagnosed diabetes were determined by multivariate logistic regression, adjusting for age, sex, and race/ethnicity, and stratified by the presence or absence of risk behaviors for hepatitis B virus (HBV) infection.

Results:

During 2009–2010, EIP sites reported 865 eligible acute hepatitis B cases among persons aged ≥23 years; 95 (11.0%) had diagnosed diabetes. Comparison group diabetes prevalence was 9.1%. Among adults without hepatitis B risk behaviors and with reported diabetes status, the OR for acute hepatitis B comparing adults with and without diabetes was 1.9 (95% confidence interval [CI] = 1.4, 2.6); ORs for adults ages 23–59 and ≥60 years were 2.1 (95% CI = 1.6, 2.8) and 1.5 (95% = CI 0.9, 2.5), respectively.

Conclusions:

Diabetes was independently associated with an increased risk for acute hepatitis B among adults without HBV risk behaviors.
Effects of Simulated Altitude on Blood Glucose Meter Performance: Implications for In-Flight Blood Glucose Monitoring
Authors: Olateju Tolu , Begley Joseph , Flanagan Daniel , Kerr David
Published: January 2014

Background:

Most manufacturers of blood glucose monitoring equipment do not give advice regarding the use of their meters and strips onboard aircraft, and some airlines have blood glucose testing equipment in the aircraft cabin medical bag. Previous studies using older blood glucose meters (BGMs) have shown conflicting results on the performance of both glucose oxidase (GOX)- and glucose dehydrogenase (GDH)-based meters at high altitude. The aim of our study was to evaluate the performance of four new-generation BGMs at sea level and at a simulated altitude equivalent to that used in the cabin of commercial aircrafts.

Methodology/Principal Findings:

Blood glucose measurements obtained by two GDH and two GOX BGMs at sea level and simulated altitude of 8000 feet in a hypobaric chamber were compared with measurements obtained using a YSI 2300 blood glucose analyzer as a reference method. Spiked venous blood samples of three different glucose levels were used. The accuracy of each meter was determined by calculating percentage error of each meter compared with the YSI reference and was also assessed against standard International Organization for Standardization (ISO) criteria. Clinical accuracy was evaluated using the consensus error grid method. The percentage (standard deviation) error for GDH meters at sea level and altitude was 13.36% (8.83%; for meter 1) and 12.97% (8.03%; for meter 2) with p = .784, and for GOX meters was 5.88% (7.35%; for meter 3) and 7.38% (6.20%; for meter 4) with p = .187. There was variation in the number of time individual meters met the standard ISO criteria ranging from 72–100%. Results from all four meters at both sea level and simulated altitude fell within zones A and B of the consensus error grid, using YSI as the reference.

Conclusions:

Overall, at simulated altitude, no differences were observed between the performance of GDH and GOX meters. Overestimation of blood glucose concentration was seen among individual meters evaluated, but none of the results obtained would have resulted in dangerous failure to detect and treat blood glucose errors or in giving treatment that was actually contradictory to that required.
Determinants of the Accuracy of Continuous Glucose Monitoring in Non-Critically Ill Patients with Heart Failure or Severe Hyperglycemia
Authors: Dungan Kathleen M. , Han Wen , Miele Anthony , Zeidan Trisha , Weiland Karen
Published: January 2014

Background:

The accuracy of continuous glucose monitoring (CGM) in non-critically ill hospitalized patients with heart failure or severe hyperglycemia (SH) is unknown.

Methods:

Hospitalized patients with congestive heart failure (CHF) exacerbation (receiving IV or subcutaneous insulin) or SH requiring insulin infusion were compared to outpatients referred for retrospective CGM.

Results:

Forty-three patients with CHF, 15 patients with SH, and 88 outpatients yielded 470, 164, and 2150 meter–sensor pairs, respectively. Admission glucose differed (188 versus 509 mg/dl in CHF and SH, p < .001) but not the first sensor glucose ( p = .35). In continuous glucose error grid analysis, 67–78% of pairs during hypoglycemia were in zones A+B ( p = .63), compared with 98–100% in euglycemia ( p < .001) and 98%, 92%, and 99% ( p = .001) during hyperglycemia for the CHF, SH, and outpatient groups, respectively. Mean absolute relative difference (MARD) was lower in the CHF versus the SH group in glucose strata above 100 mg/dl, but there was no difference between the CHF and outpatient groups. Linear regression models showed that CHF versus outpatient, SH versus CHF, and coefficient of variation were significant predictors of higher MARD. Among subjects with CHF, MARD was not associated with brain natriuretic peptide or change in plasma volume, but it was significantly higher in subjects randomized to IV insulin ( p = .04).

Conclusions:

The results suggest that SH and glycemic variability are more important determinants of CGM accuracy than known CHF status alone in hospitalized patients.
Importance of Blood Glucose Meter and Carbohydrate Estimation Accuracy
Authors: Virdi Naunihal S. , Mahoney John J.
Published: January 2014

Background:

The clinical significance of blood glucose meter (BGM) error in the presence of increasing carbohydrate errors in diabetes patients who use both the BGM result and the carbohydrate estimation to dose insulin is unknown.

Methods:

This Monte Carlo simulation modeled diabetes patients who calculate insulin dosages based on BGM results and carbohydrate estimations. It evaluated the likelihood of on-target insulin dosing and clinically significant insulin dose errors based on data from five BGMs with different levels of performance (expressed as bias and imprecision [coefficient of variation (%CV)]) and increasing levels of carbohydrate estimation errors. The study was performed across three separate preprandial glucose (PPG) ranges (90–150, 150–270, and 270–450 mg/dl).

Results:

When carbohydrate estimation is accurate (%CV = 0%), the likelihood for on-target insulin doses ranged 50.1–98.5%. The likelihood depended on BGM performance and PPG range. In the presence of carbohydrate estimation errors (%CV = 5–20%), the likelihood of on-target insulin dosages markedly decreased (range, 27.2–80.1%) for all BGMs, the likelihood of insulin underdosing (range, 0–12.8%) and overdosing (range, 0–32.3%) increased, and the influence of BGM error on insulin dosing accuracy was blunted. Even in the presence of carbohydrate error, the BGM with the best performance (bias 1.35% and %CV = 4.84) had the highest probability for on-target insulin dosages.

Conclusions:

Both BGM and carbohydrate estimation error contribute to insulin dosing inaccuracies. The BGM with the best performance was associated with the most on-target insulin dosages.
Integrated Self-Monitoring of Blood Glucose System: Handling Step Analysis
Authors: Freckmann Guido , Schmid Christina , Ruhland Katharina , Baumstark Annette , Haug Cornelia
Published: January 2014

Self-monitoring of blood glucose (SMBG) implicates a number of handling steps with the meter and the lancing device. Numerous user errors can occur during SMBG, and each step adds to the complexity of use. This report compares the required steps to perform SMBG of one fully integrated (the second generation of the Accu-Chek® Mobile), three partly integrated (Accu-Chek Compact Plus, Ascensia® Breeze®2, and Accu-Chek Aviva), and six conventional (Bayer Contour®, Bayer Contour USB, BGStar™, FreeStyle Lite®, OneTouch® Ultra® 2, and OneTouch Verio™Pro) systems. The results show that the fully integrated system reduces the number of steps to perform SMBG. The mean decrease is approximately 70% compared with the other systems. We assume that a reduction of handling steps also reduces the risk of potential user errors and improves the user-friendliness of the system.
Insulin Delivery Device Technology 2012: Where are We after 90 Years?
Authors: Fry Andrew
Published: January 2014

Since the first successful use of insulin in 1921 to treat diabetes at Toronto General Hospital, the major advances in development of the medication itself have taken place in parallel with equally significant developments in the means of delivery. Administration of insulin remains parenteral. This article reviews the main variants in prescription-available delivery technology: Vial and syringe, pen injector, needle-free injection, and continuous subcutaneous insulin infusion pumps. For each of these, the background and major milestones are covered briefly and followed by a discussion of the latest product innovations, technologies, and implementations, which are all considered in the context of the interaction with users. The article concludes by reflecting upon how the progress in the technology of diabetes management can best serve the patient. The spectacular technological advances in medication, monitoring, and delivery since 1922 have transformed the lives of millions. However, the fact that we can add sophisticated technology to delivery devices and accessories does not mean it is always the best thing for the patient. Electronic sophistication may be welcomed by a young, eager type 1 diabetes patient, while a senior citizen who discovers he has type 2 diabetes may yearn for simplicity. Technology continues to provide great solutions, but the type of solution delivered must be matched to the user if the maximum benefit is to be achieved for all.
Insulin Infusion Set: The Achilles Heel of Continuous Subcutaneous Insulin Infusion
Authors: Heinemann Lutz , Krinelke Lars
Published: January 2014

Continuous subcutaneous insulin infusion from an insulin pump depends on reliable transfer of the pumped insulin to the subcutaneous insulin depot by means of an insulin infusion set (IIS). Despite their widespread use, the published knowledge about IISs and related issues regarding the impact of placement and wear time on insulin absorption/insulin action is relatively small. We also have to acknowledge that our knowledge is limited with regard to how often patients encounter issues with IISs. Reading pump wearer blogs, for instance, suggests that these are a frequent source of trouble. There are no prospective clinical studies available on current IIS and insulin formulations that provide representative data on the type and frequency of issues with infusion sets. The introduction of new IISs and patch pumps may foster a reassessment of available products and of patient problems related to their use. The aim of this review is to summarize the current knowledge and recommendations about IISs and to highlight potential directions of IIS development in order to make insulin absorption safer and more efficient.
Pediatric Use of Insulin Pump Technology: A Retrospective Study of Adverse Events in Children Ages 1–12 Years
Authors: Cope Judith U. , Samuels-Reid Joy H. , Morrison Audrey E.
Published: January 2014

Background:

Growing technological improvements in insulin pump design have increased the use of these devices in young children. To better understand the types of infusion pump-related problems and associated adverse events in this age group, we performed a comprehensive evaluation of pump-related adverse event reports received by the U.S. Food and Drug Administration (FDA) for children ages 1–12 years.

Methods:

A query was conducted of FDA's Manufacturer and User Facility Device Experience database from January 1, 1996, through December 31, 2009, in children ages 1–12 years involving insulin pumps. Report narratives were individually reviewed for age, gender, and seriousness of outcomes. Device or patient problems and potential contributory factors were assessed.

Results:

Over the past 14 years, 1774 (7%) of all insulin pump adverse event reports were identified in children ages 1–12. Of these reports, 777 (43%) resulted in hospitalization. In hospitalized cases ( n = 614), diabetic ketoacidosis and/or hyperglycemia were the predominant patient problems, and in other cases ( n = 98), hypoglycemia was evident. There were 106 emergency room visits, 19 cases requiring paramedic attention, and five deaths. The majority of reports indicated that the devices were not returned to the manufacturer, and root causes were not always confirmed.

Conclusions:

Younger children with diabetes deserve careful consideration of the risk and benefit of insulin pump technology. Studies are needed to better understand pediatric safety issues and to identify the root cause of adverse events. Problems related to patient education, device misuse, and malfunctions were found, highlighting the need to strengthen user training for children and their caregivers.
Comparative Analysis of the Efficacy of Continuous Glucose Monitoring and Self-Monitoring of Blood Glucose in Type 1 Diabetes Mellitus
Authors: Floyd Baraka , Chandra Prakash , Hall Stephanie , Phillips Christopher , Alema-Mensah Ernest , Strayhorn Gregory , Ofili Elizabeth O. , Umpierrez Guillermo E.
Published: January 2014

Background:

Self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) have been proven effective in improving hemoglobin A1c (HbA1c) and in reducing hypoglycemia in patients with type 1 diabetes mellitus (T1DM). It is not clear, however, if CGM provides further efficacy and safety benefits beyond SMBG in the management of T1DM.

Methods:

MEDLINE (1966-November 2009), COCHRANE REGISTRY (all years), and EMBASE (1980-November 2009), and article bibliographies were searched for randomized controlled trials (RCTs) investigating the use of CGM in patients with T1DM, with clinical outcomes, including HbA1c and hypoglycemia and/or hyperglycemia.

Results:

Fourteen RCTs met eligibility criteria [ n = 1188 patients, 97.4% with T1DM, age 29.0 ± 14.3 years, diabetes duration 11.7 ± 7.0 years, and baseline HbA1c 8.3 ± 0.8% (mean ± standard deviation)]. Compared with SMBG, the use of CGM was associated with a greater reduction in HbA1c [−0.3% (confidence interval: 0.4, −0.2), p < .0001]. The number of hypoglycemic events was not significantly different between the CGM and SMBG groups (0.52 ± 0.52 versus 0.52 ± 0.63 events/day, p = .5), but duration of hypoglycemia was shorter for the CGM group (75 ± 39 versus 89 ± 19 min/day), with an incremental reduction of hypoglycemia duration of −15.2 min/day, p < .0001. Continuous glucose monitoring also resulted in a shorter duration of hyperglycemia than SMBG (172 ± 125 versus 217 ± 152 min/day, p = .04).

Conclusions:

The use of CGM is associated with improvement in metabolic control in T1DM, with significant short- and long-term reductions in HbA1c and reduction in the duration of periods of hypoglycemia and hyperglycemia versus SMBG.
Overview of Fluorescence Glucose Sensing: A Technology with a Bright Future
Authors: Klonoff David C.
Published: January 2014

Fluorescence represents a promising alternative technology to electrochemistry and spectroscopy for accurate analysis of glucose in diabetes; however, no implanted fluorescence glucose assay is currently commercially available. The method depends on the principle of fluorescence, which is the emission of light by a substance after absorbing light. A fluorophore is a molecule that will absorb energy of a specific wavelength and reemit energy at a different wavelength. A fluorescence glucose-sensing molecule can be constructed to increase or decrease in fluorescence from baseline according to the ambient concentration of glucose. A quantum dot is a semiconductor crystal that can serve as a sensor by fluorescing at a desired wavelength or color, depending on the crystal size and materials used. If receptor molecules for glucose can be adsorbed to single-wall carbon nanotubules, then the resulting binding of glucose to these receptors will alter the nanotubes' fluorescence. Fluorescence glucose sensors can provide a continuous glucose reading by being embedded into removable wire-shaped subcutaneous or intravenous catheters as well as other types of implanted structures, such as capsules, microcapsules, microbeads, nano-optodes, or capillary tubes.

Fluorescence glucose-sensing methods, which are under development, offer four potential advantages over commercially used continuous glucose monitoring technologies: (1) greater sensitivity to low concentrations of glucose, (2) the possibility of constructing sensors that operate most accurately in the hypoglycemic range by using binding proteins with disassociation constants in this range, (3) less need to recalibrate in response to local tissue reactions around the sensor, and (4) no need to implant either a transmitter or a power source for wireless communication of glucose data.

Fluorescence glucose sensors also have four significant disadvantages compared with commercially used continuous glucose monitoring technologies: (1) a damaging foreign body response; (2) a sensitivity to local pH and/or oxygen, which can affect the dye response; (3) potential toxicity of implanted dyes, especially if the implanted fluorophore cannot be fully removed; and (4) the necessity of always carrying a dedicated light source to interrogate the implanted sensor. Fluorescence sensing is a promising method for measuring glucose continuously, especially in the hypoglycemic range. If currently vexing technical and engineering and biocompatibility problems can be overcome, then this approach could lead to a new family of continuous glucose monitors.
Biofouling of Polymer Hydrogel Materials and its Effect on Diffusion and Enzyme-Based Luminescent Glucose Sensor Functional Characteristics
Authors: Roberts Jason R. , Park Jaebum , Helton Kristen , Wisniewski Natalie , McShane Michael J.
Published: January 2014

Background:

Continuous glucose monitoring is crucial to developing a successful artificial pancreas. However, biofouling and host response make in vivo sensor performance difficult to predict. We investigated changes in glucose diffusivity and sensor response of optical enzymatic glucose sensors due to biological exposure.

Method:

Three hydrogel materials, poly(2-hydroxyethyl methacrylate) (pHEMA), poly(acrylamide) (pAM), and poly(2-hydroxyethyl methacrylate)-co-poly(acrylamide) (p(HEMA-co-AM)), were tested for glucose diffusivity before and after exposure to serum or implantation in rats for 1 month. Luminescent sensors based on these materials were measured to compare the response to glucose before and after serum exposure.

Results:

Glucose diffusivity through the pHEMA [(8.1 ± 0.38) × 10−8 cm2/s] slabs was much lower than diffusivity through pAM [(2.7 ± 0.15) × 10−6 cm2/s] and p(HEMA-co-AM) [(2.5 ± 0.08) × 10−6]. As expected from these differences, sensor response was highly dependent on material type. The pHEMA sensors had a maximum sensitivity of 2.5%/(mg/dl) and an analytical range of 4.2–356 mg/dl, while the p(HEMA-co-AM) sensors had a higher sensitivity [14.9%/(mg/dl)] and a narrower analytical range (17.6–70.5 mg/dl). After serum exposure, the pHEMA sensors were unaffected, whereas the p(HEMA-co-AM) sensors exhibited significantly decreased sensitivity and increased analytical range.

Conclusions:

Decreases in glucose diffusivity in the polymers resulting from in vitro serum exposure and residence in vivo were shown to be similar, suggesting that serum incubation was a reasonable approximation of in vivo fouling. While biofouling is expected to affect the response of flux-based sensors, we have shown that this depended on the type of sensor and matrix used. Therefore, proper design and materials selection may minimize response alterations occurring upon implantation.
Application of Adaptive Design Methodology in Development of a Long-Acting Glucagon-like Peptide-1 Analog (Dulaglutide): Statistical Design and Simulations
Authors: Skrivanek Zachary , Berry Scott , Berry Don , Chien Jenny , Geiger Mary Jane , Anderson James H. , Gaydos Brenda
Published: January 2014

Background:

Dulaglutide (dula, LY2189265), a long-acting glucagon-like peptide-1 analog, is being developed to treat type 2 diabetes mellitus.

Methods:

To foster the development of dula, we designed a two-stage adaptive, dose-finding, inferentially seamless phase 2/3 study. The Bayesian theoretical framework is used to adaptively randomize patients in stage 1 to 7 dula doses and, at the decision point, to either stop for futility or to select up to 2 dula doses for stage 2. After dose selection, patients continue to be randomized to the selected dula doses or comparator arms. Data from patients assigned the selected doses will be pooled across both stages and analyzed with an analysis of covariance model, using baseline hemoglobin A1c and country as covariates. The operating characteristics of the trial were assessed by extensive simulation studies.

Results:

Simulations demonstrated that the adaptive design would identify the correct doses 88% of the time, compared to as low as 6% for a fixed-dose design (the latter value based on frequentist decision rules analogous to the Bayesian decision rules for adaptive design).

Conclusions:

This article discusses the decision rules used to select the dula dose(s); the mathematical details of the adaptive algorithm—including a description of the clinical utility index used to mathematically quantify the desirability of a dose based on safety and efficacy measurements; and a description of the simulation process and results that quantify the operating characteristics of the design.
Prevention of Diabetes in Rural India with a Telemedicine Intervention
Authors: Mohan Viswanathan , Deepa Mohan , Pradeepa Rajendra , Prathiba Venkat , Datta Manjula , Ravikumar Sethuraman , Rakesh Hari , Sucharita Yarlagadda , Webster Premila , Allender Steven , Kapur Anil , Anjana Ranjit Mohan
Published: January 2014

Background:

Diabetes care is not presently available, accessible, or affordable to people living in rural areas in developing countries, such as India. The Chunampet Rural Diabetes Prevention Project (CRDPP) was conceived with the aim of implementing comprehensive diabetes screening, prevention, and treatment using a combination of telemedicine and personalized care in rural India.

Methods:

This project was undertaken in a cluster of 42 villages in and around the Chunampet village in the state of Tamil Nadu in southern India. A telemedicine van was used to screen for diabetes and its complications using retinal photography, Doppler imaging, biothesiometry, and electrocardiography using standardized techniques. A rural diabetes center was set up to provide basic diabetes care.

Results:

Of the total 27,014 adult population living in 42 villages, 23,380 (86.5%) were screened for diabetes, of which 1138 (4.9%) had diabetes and 3410 (14.6%) had prediabetes. A total of 1001 diabetes subjects were screened for complications (response rate of 88.0%). Diabetic retinopathy was detected in 18.2%, neuropathy in 30.9%, microalbuminuria in 24.3%, peripheral vascular disease in 7.3%, and coronary artery disease in 10.8%. The mean hemoglobin A1c levels among the diabetes subjects in the whole community decreased from 9.3 ± 2.6% to 8.5 ± 2.4% within 1 year. Less than 5% of patients needed referral for further management to the tertiary diabetes hospital in Chennai.

Conclusions:

The Chunampet Rural Diabetes Prevention Project is a successful model for screening and for delivery of diabetes health care and prevention to underserved rural areas in developing countries such as India.
Evaluation of a Continuous Blood Glucose Monitoring System Using Central Venous Microdialysis
Authors: Schierenbeck Fanny , Franco-Cereceda Anders , Liska Jan
Published: January 2014

Background:

Glycemic control in critically ill patients has been shown to be beneficial. In this prospective study, we evaluated the accuracy and technical feasibility of a continuous glucose monitoring system using intravascular microdialysis.

Method:

Fifty patients undergoing cardiac surgery were monitored using a 4 Fr intravenous microdialysis catheter (Eirus SLC™, Dipylon Medical AB, Solna, Sweden) percutaneously placed with the tip of the catheter positioned in the superior vena cava. The catheter was connected to the Eirus™ monitoring system, and the patients were monitored for up to 48 h postoperatively in the intensive care unit (ICU). As reference, arterial blood samples were taken every hour and analyzed in a blood gas analyzer.

Results:

Data were available from 48 patients. A total of 994 paired (arterial blood gas microdialysis) samples were obtained. Glucose correlation coefficient ( R2) was 0.85. Using Clarke error grid analysis, 100% of the paired samples were in region AB, and 99% were in region A. Mean glucose level was 8.3 mmol/liter (149 mg/dl), mean relative difference was 0.2%, and mean absolute relative difference was 5%. A total of 99.2% of the paired samples were correct according to International Organization for Standardization (ISO) criteria. Bland-Altman analysis showed that bias ± limits of agreement were 0.02 ± 1.1 mmol/liter (0.36 ± 20 mg/dl).

Conclusions:

Central venous microdialysis using the Eirus monitoring system is a highly accurate and reliable method for continuous blood glucose monitoring up to 48 h in ICU patients undergoing cardiac surgery. The system may thus be useful in critically ill ICU patients.
Analysis: Continuous Glucose Monitoring in the Intensive Care Unit
Authors: Ward W. Kenneth
Published: January 2014

Control of glycemia in hospitalized patients is important; hypoglycemia is associated with increased mortality, and hyperglycemia is associated with adverse outcomes. For these reasons, though no such device is currently available, continuous glucose monitoring (CGM) is an attractive option, especially in the critical care setting. Schierenbeck and coauthors, in this issue of Journal of Diabetes Science and Technology, report on the use of a specialized central catheter designed to monitor glucose continuously in post cardiac surgery patients. This catheter, which was indwelled within the great veins, was specially designed with a separate lumen and membrane that allowed continuous glucose microdialysis. Accuracy was quite good, better than has been reported with the use of commercially-available CGM devices. Ideally, further development of this quite promising catheter-based device would allow it to be used also to deliver fluids and drugs, thus avoiding the need for a second catheter elsewhere.
An Analysis of “No Effect of Insulin Pen with Memory Function on Glycemic Control in a Patient Cohort with Poorly Controlled Type 1 Diabetes: A Randomized Open-Label Study”
Authors: Ampudia-Blasco Francisco Javier
Published: January 2014

Missing meal bolus and nonadherence is an important barrier to achieving glycemic goals in type 1 diabetes (T1DM). In this issue of Journal of Diabetes Science and Technology, Danne and coauthors reported the results of a 24-week randomized-controlled study designed to evaluate if using an insulin pen with memory function, the HumaPen® Memoir™, might improve injection compliance and, therefore, overall glycemic control in T1DM. Patients treated with the pen device with memory function improved, albeit nonsignificantly, their mean HbA1c by 0.43%. Among the reasons to justify why this study was not positive, the most important is the high proportion of adult patients included in the study (87.9%)—children and adolescents being under-represented. I am convinced that pen devices with memory function might be helpful for forgetful patients (children, adolescents), as suggested in another recent study.
Use of a Food and Drug Administration-Approved Type 1 Diabetes Mellitus Simulator to Evaluate and Optimize a Proportional-Integral-Derivative Controller
Authors: Laxminarayan Srinivas , Reifman Jaques , Steil Garry M.
Published: January 2014

Background:

Clinical studies have shown that the Medtronic proportional-integral-derivative (PID) control with insulin feedback (IFB) provides stable 24 h glucose control, but with high postprandial glucose. We coupled this algorithm to a Food and Drug Administration-approved type 1 diabetes mellitus simulator to determine whether a proportional-derivative controller with preprogrammed basal rates (PDBASAL) would have better performance.

Methods:

We performed simulation studies on 10 adult subjects to (1) obtain the basal profiles for the PDBASAL controller; (2) define the pharmacokinetic/pharmacodynamic profile used to effect IFB, (3) optimize the PID and PDBASAL control parameters, (4) evaluate improvements obtained with IFB, and (5) develop a method to simulate changes in insulin sensitivity and assess the ability of each algorithm to respond to such changes.

Results:

PDBASAL control significantly reduced peak postprandial glucose [252 (standard error = 11) versus 279 (14) mg/dl; p < .001] and increased nadir glucose [102 (3) versus 92 (3) mg/dl; p < .001] compared with PID control (both implemented with IFB). However, with PDBASAL control, fasting glucose remained elevated following a 30% decrease in insulin sensitivity [156 (6) mg/dl; different from the target of 110 mg/dl; p < .001] and remained below target following a 30% increase in insulin sensitivity [84 (2) mg/dl; p < .001]. In both cases, PID control returned glucose levels to target.

Conclusions:

PDBASAL provides better postprandial glucose control than PID but is not appropriate for subjects whose basal requirements change with insulin sensitivity. Simulations used to compare different control strategies should assess this variability.
Improving the Computational Effort of Set-Inversion-Based Prandial Insulin Delivery for Its Integration in Insulin Pumps
Authors: León-Vargas Fabian , Calm Remei , Bondia Jorge , Vehí Josep
Published: January 2014

Objective:

Set-inversion-based prandial insulin delivery is a new model-based bolus advisor for postprandial glucose control in type 1 diabetes mellitus (T1DM). It automatically coordinates the values of basal-bolus insulin to be infused during the postprandial period so as to achieve some predefined control objectives. However, the method requires an excessive computation time to compute the solution set of feasible insulin profiles, which impedes its integration into an insulin pump. In this work, a new algorithm is presented, which reduces computation time significantly and enables the integration of this new bolus advisor into current processing features of smart insulin pumps.

Methods:

A new strategy was implemented that focused on finding the combined basal-bolus solution of interest rather than an extensive search of the feasible set of solutions. Analysis of interval simulations, inclusion of physiological assumptions, and search domain contractions were used. Data from six real patients with T1DM were used to compare the performance between the optimized and the conventional computations.

Results:

In all cases, the optimized version yielded the basal-bolus combination recommended by the conventional method and in only 0.032% of the computation time. Simulations show that the mean number of iterations for the optimized computation requires approximately 3.59 s at 20 MHz processing power, in line with current features of smart pumps.

Conclusions:

A computationally efficient method for basal-bolus coordination in postprandial glucose control has been presented and tested. The results indicate that an embedded algorithm within smart insulin pumps is now feasible. Nonetheless, we acknowledge that a clinical trial will be needed in order to justify this claim.
Continuous Monitoring of Glucose in Subcutaneous Tissue Using Microfabricated Differential Affinity Sensors
Authors: Huang Xian , Leduc Charles , Ravussin Yann , Li Siqi , Davis Erin , Song Bing , Wang Qian , Accili Domenico , Leibel Rudolph , Lin Qiao
Published: January 2014

Objective:

We describe miniaturized differential glucose sensors based on affinity binding between glucose and a synthetic polymer. The sensors possess excellent resistance to environmental disturbances and can potentially allow wireless measurements of glucose concentrations within interstitial fluid in subcutaneous tissue for long-term, stable continuous glucose monitoring (CGM).

Methods:

The sensors are constructed using microelectromechanical systems (MEMS) technology and exploit poly(N-hydroxy-ethyl acrylamide- ran-3-acrylamidophenylboronic acid) (PHEAA- ran-PAAPBA), a glucose-binding polymer with excellent specificity, reversibility, and stability. Two sensing approaches have been investigated, which respectively, use a pair of magnetically actuated diaphragms and perforated electrodes to differentially measure the glucose-binding-induced changes in the viscosity and permittivity of the PHEAA- ran-PAAPBA solution with respect to a reference, glucose-unresponsive polymer solution.

Results:

In vivo characterization of the MEMS affinity sensors were performed by controlling blood glucose concentrations of laboratory mice by exogenous glucose and insulin administration. The sensors experienced an 8–30 min initialization period after implantation and then closely tracked commercial capillary glucose meter readings with time lags ranging from 0–15 min during rapid glucose concentration changes. Clarke error grid plots obtained from sensor calibration suggest that, for the viscometric and dielectric sensors, respectively, approximately 95% (in the hyperglycemic range) and 84% (ranging from hypoglycemic to hyperglycemic glucose concentrations) of measurement points were clinically accurate, while 5% and 16% of the points were clinically acceptable.

Conclusions:

The miniaturized MEMS sensors explore differential measurements of affinity glucose recognition. In vivo testing demonstrated excellent accuracy and stability, suggesting that the devices hold the potential to enable long-term and reliable CGM in clinical applications.
Continuous Glucose Monitoring in Pregnancy: New Frontiers in Clinical Applications and Research
Authors: Sung Joyce F. , Taslimi Masoud Mark , Faig Jeffrey C.
Published: January 2014

Current treatment of diabetes in pregnancy relies on intermittent self-monitoring of blood glucoses using finger sticks to monitor capillary blood glucoses. Continuous glucose monitoring (CGM) systems are an emerging technology that allow frequent glucose measurements (every 5 min) and the ability to monitor glucose trends in real time. Although these devices are currently expensive and mildly invasive to use, there is huge potential for their use in both the research and clinical realms. From a research perspective, there is the potential to better understand glucose metabolism in pregnancy, both in patients with and without diabetes. For the treating clinician, CGM has the potential to improve detection of hyperglycemic excursions as well as asymptomatic hypoglycemia and the data to improve management of glucose levels in diabetes patients. In this article, we review current literature examining use of CGM in both research and clinical applications.
Reimbursement for Continuous Glucose Monitoring: A European View
Authors: Heinemann Lutz , Franc Sylvia , Phillip Moshe , Battelino Tadej , Ampudia-Blasco Francisco Javier , Bolinder Jan , Diem Peter , Pickup John , DeVries J. Hans
Published: January 2014

Different systems for continuous glucose monitoring (CGM) are available on the European market. There is no unlimited reimbursement for CGM use in any European country, but in some countries, reimbursement exists for certain clinical indications. The aim of this commentary is to describe the different reimbursement situations across Europe for this innovative but costly technology, as a prelude to establishing more uniform use. From the perspective of many scientists and clinicians, a number of randomized controlled trials have demonstrated the efficacy of real-time CGM versus self-monitoring of blood glucose, at least for hemoglobin A1c reduction. Nevertheless, according to many health care professionals and potential CGM users, national health services and health insurance organizations are reluctant to reimburse CGM. Imminent technological and manufacturing developments are expected to reduce the day-to-day costs of CGM.