bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fluorescent Responsive Hybrid Nanogel for Closed-Loop Control of Glucose
Authors: Wu Weitai , Chen Shoumin , Hu Yumei , Zhou Shuiqin
Published: January 2014

Background:

The concept of closed-loop control of glucose, in which continuous glucose sensing is coupled to a fully automated insulin delivery device, without human input, has been an attractive idea for diabetes management. This study presents a new class of hybrid nanogels that can integrate glucose sensing and glucose-responsive insulin release into a single nano-object.

Methods:

Zinc oxide@poly[N-isopropylacrylamide (NIPAM)-acrylamide (AAm)- 2-aminomethyl-5-fluorophenylboronic acid (FPBA)] hybrid nanogels were synthesized and investigated for size, morphology, volume phase transition, photoluminescence properties, and in vitro insulin release under different glucose concentrations. Glucose sensing was performed both in phosphate-buffered saline (PBS) and in blood samples. The insulin release in PBS of varying glucose levels, as well as a stepwise treatment between two glucose levels (126.0 and 270.0 mg/dl), was performed to test the glucose-responsive insulin release ability of the hybrid nanogels.

Results:

Zinc oxide@poly(NIPAM-AAm-FPBA) hybrid nanogels can sensitively and selectively detect glucose in highly reproducible fluorescent signals over the clinically relevant glucose concentration range of 18–540 mg/dl. The glucose-responsive volume phase transition of the nanogels can further regulate the release of the preloaded insulin. The insulin release from the nanogels exhibits the slowest rate (~5% released in 76 h) at a normal glucose level (108.0 mg/dl) but becomes quicker and quicker as the glucose increases to higher and higher levels.

Conclusions:

The rationally designed hybrid nanogel can optically signal the glucose level with high sensitivity and selectivity and simultaneously regulate the insulin release rate in response to the glucose reading, which shows a promising concept toward the development of a miniaturized closed-loop glycemic control system.
Analysis of Comparison of Patient Preference for Two Insulin Injection Pen Devices in Relation to Patient Dexterity Skills
Authors: Antinori-Lent Kellie J.
Published: January 2014

Insulin therapy is the cornerstone of medical treatment for many patients with diabetes. Self-administration of this life-saving medication is no longer limited to the traditional vial and syringe. Instead, more and more patients worldwide are using prefilled insulin pen devices. Ease of use, convenience, confidence in dosing accuracy, and improved quality of life are just a few of their advantages. As with any medical technology, safe and proper use is vital. Many studies have examined pen device preference and usability. Until now, no study has included patients with both visual and dexterity impairments. To ensure safe and simple self-administration of insulin for all patients, it is time for the special needs of patients with diabetes to be considered not only during product development, but during postmarketing studies as well.
Transitioning Insulin Pump Therapy from the Outpatient to the Inpatient Setting: A Review of 6 Years' Experience with 253 Cases
Authors: Cook Curtiss B. , Beer Karen A. , Seifert Karen M. , Boyle Mary E. , Mackey Patricia A. , Castro Janna C.
Published: January 2014

Background:

We reviewed the care of a large cohort of patients with diabetes mellitus on insulin pump therapy who required an inpatient stay.

Methods:

Records were reviewed of patients hospitalized between January 1, 2006, and December 31, 2011.

Results:

A total of 136 patients using insulin pumps had 253 hospitalizations. Mean (standard deviation) patient age was 55 (16) years, diabetes duration was 29 (15) years, and pump duration was 6 (5) years. Insulin pump therapy was continued in 164 (65%) hospitalizations. Adherence to core process measures improved over time: by 2011, 100% of cases had an endocrinology consultation, 100% had the required insulin pump order set completed, and 94% had documentation of the signed agreement specifying patient responsibilities for continued use of the technology while hospitalized. Documentation of the insulin pump flow sheet also increased but could still be located in only 64% of cases by the end of 2011. Mean glucose was not significantly different among patients who remained on insulin pump therapy compared to those for whom it was discontinued ( p > .1), but episodes of severe hyperglycemia (>300 mg/dl) and hypoglycemia (<40 mg/dl) were significantly less common among pump users. No pump site infections, mechanical pump failures, or episodes of diabetic ketoacidosis were observed among patients remaining on therapy.

Conclusions:

With appropriate patient selection and usage guidelines, most patients using insulin pumps can safely have their therapy transitioned to the inpatient setting. Further study is needed to determine whether this approach can be translated to other hospital settings.
Comparison of Insulin Pump Therapy (Continuous Subcutaneous Insulin Infusion) to Alternative Methods for Perioperative Glycemic Management in Patients with Planned Postoperative Admissions
Authors: Corney Sarah M. , Dukatz Tamra , Rosenblatt Solomon , Harrison Barbara , Murray Robert , Sakharova Alla , Balasubramaniam Mamtha
Published: January 2014

Background:

Patients with diabetes who use insulin pumps [continuous subcutaneous insulin infusion (CSII)] undergo surgeries that require postoperative hospital admission. There are no defined guidelines for CSII perioperative use.

Methods:

This retrospective single-institution study identified type 1 and type 2 diabetes subjects by electronically searching 2005–2010 anesthesia preoperative assessments for “pump.” Surgical cases ( n = 92) were grouped according to intraoperative insulin delivery method: (a) CSII continuation of basal rate with/without correctional insulin bolus(es) ( n = 53); (b) conversion to intravenous insulin infusion ( n = 20); and (c) CSII suspension with/without correctional insulin bolus(es) ( n = 19). These groups were compared on mean intraoperative blood glucose (BG) and category of most extreme intraoperative BG.

Results:

Differences were found on baseline characteristics of diabetes duration ( p = .010), anesthesia time ( p = .011), proportions receiving general anesthesia ( p = .013), and preoperative BG ( p = .033). The conversion group had the longest diabetes duration and anesthesia time; it had a higher proportion of general anesthesia recipients and a higher mean preoperative BG than the continuation group. There was no significant difference in mean BG/surgical case between continuation (163.5 ± 58.5 mg/dl), conversion (152.3 ± 28.9 mg/dl), and suspension groups (188.3 ± 44.9 mg/dl; p = .128). The suspension group experienced a greater percentage of cases (84.2%) with one or more intraoperative BG > 179 mg/dl than continuation (45.3%) and conversion (40%) groups Figure 1 groupings ( p = .034).

Conclusions:

In this limited sample, preliminary findings are consistent with similar intraoperative glycemic control between CSII continuation and CSII conversion to intravenous insulin infusions. Continuous subcutaneous insulin infusion suspension had a greater rate of hyperglycemia. Preoperative differences between insulin delivery groups complicate interpretations of fndings.
Cystic Fibrosis-Related Diabetes in Adults: Inpatient Management of 121 Patients during 410 Admissions
Authors: Rasouli Neda , Seggelke Stacey , Gibbs Joanna , Hawkins R. Matthew , Casciano Matthew L. , Cohlmia Elizabeth , Taylor-Cousar Jennifer , Wang Cecilia , Pereira Rocio , Hsia Elisa , Draznin Boris
Published: January 2014

Background:

With improved longevity, cystic fibrosis (CF)-related diabetes (CFRD) has emerged as the most common nonpulmonary complication of CF. Patients with CFRD are frequently admitted to the hospital with infections and deterioration of pulmonary function, during which time glycemic control might have an impact on pulmonary function, recovery from infection, and survival.

Methods and Results:

In an attempt to share our insight into inpatient management of CFRD, this article summarizes the experience of our inpatient glucose management team with hospital management of 121 adult CFRD patients who were hospitalized on 410 occasions at the University of Colorado Hospital between January 2009 and September 2011. This is a retrospective chart review descriptive study of inpatient management of CFRD in our center. Our cohort includes CFRD patients treated with basal and mealtime insulin through multiple daily injections or continuous subcutaneous insulin infusion (CSII), as well as patients receiving steroids or enteral nutrition, which adds complexity to the management of CFRD during hospitalization.

Conclusions:

Multiple hospitalizations and intensive inpatient management of CF are integral elements of treatment. Inpatient therapy for CFRD requires a customized approach that is uniquely different from that of type 1 or type 2 diabetes. Our experience highlights clinical circumstances such as irregular food intake, high dose steroid therapy, and supplemental tube feeding. For many patients, it is possible to continue CSII therapy during hospitalization through a combination of mutual trust between the patient and hospital staff and oversight provided by the glucose management team.
The Effect of Diabetes on Hospital Readmissions
Authors: Dungan Kathleen M.
Published: January 2014

Hospital readmission is an important contributor to total medical expenditures and is an emerging indicator of quality of care. Diabetes, similar to other chronic medical conditions, is associated with increased risk of hospital readmission. Risk factors include previous hospitalization, extremes in age, and socioeconomic barriers. Preliminary studies suggest that acute and/or chronic glycemic control may be of importance when diabetes is the primary diagnosis or when it is a comorbidity. Very limited evidence from prospective randomized controlled trials aimed at improving glycemic control is available. However, whether one concludes that inpatient or outpatient glycemic control is partly responsible for reduced hospitalizations, attention to glycemic control in the hospital may facilitate sustained glycemic control post-discharge. Limited prospective and retrospective evidence suggest that the involvement of a diabetes specialist team may improve readmission rates, but attention to more generalized comprehensive approaches may also be worthwhile. Prospective interventional studies targeting interventions for improving glycemic control are needed to determine whether glycemic control impacts readmission rates.
Real-Time State Estimation and Long-Term Model Adaptation: A Two-Sided Approach toward Personalized Diagnosis of Glucose and Insulin Levels
Authors: Eberle Claudia , Ament Christoph
Published: January 2014

Background:

With continuous glucose sensors (CGSs), it is possible to obtain a dynamical signal of the patient's subcutaneous glucose concentration in real time. How could that information be exploited? We suggest a model-based diagnosis system with a twofold objective: real-time state estimation and long-term model parameter identification.

Methods:

To obtain a dynamical model, Bergman's nonlinear minimal model (considering plasma glucose G, insulin I, and interstitial insulin X) is extended by two states describing first and second insulin response. Furthermore, compartments for oral glucose and subcutaneous insulin inputs as well as for subcutaneous glucose measurement are added. The observability of states and external inputs as well as the identifiability of model parameters are assessed using the empirical observability Gramian. Signals are estimated for different nondiabetic and diabetic scenarios by unscented Kalman filter.

Results:

(1) Observability of different state subsets is evaluated, e.g., from CGSs, { G, I} or { G, X} can be observed and the set { G, I, X} cannot. (2) Model parameters are included, e.g., it is possible to estimate the second-phase insulin response gain kG2 additionally. This can be used for model adaptation and as a diagnostic parameter that is almost zero for diabetes patients. (3) External inputs are considered, e.g., oral glucose is theoretically observable for nondiabetic patients, but estimation scenarios show that the time delay of 1 h limits application.

Conclusions:

A real-time estimation of states (such as plasma insulin I) and parameters (such as kG2) is possible, which allows an improved real-time state prediction and a personalized model.
Interference Testing: Why following Standards is Not Always the Right Thing to Do
Authors: Krouwer Jan S.
Published: January 2014

Lucarelli and colleagues in this issue of Journal of Diabetes Science and Technology describe the results of interference testing for a continuous glucose monitoring system. The authors follow the Clinical Laboratory Standards Institute guideline EP7-A2, including their conclusions, in which the concepts of a statistically significant interfering substance and a clinically important interference have been combined in a way whereby information from the experiment has been lost and could be misleading. A better way to treat the data is presented, including a simulation method to evaluate the effects of interferences.
Use of a Computerized Tracking System to Monitor and Provide Feedback on Dietary Goals for Calorie-Restricted Diets: The POUNDS LOST Study
Authors: Anton Stephen D. , LeBlanc Eric , Allen H. Raymond , Karabetian Christy , Sacks Frank , Bray George , Williamson Donald A.
Published: January 2014

The use of self-monitoring as a tool to facilitate behavioral modification is common in many lifestyle-based weight loss interventions. Electronic tracking programs, including computer-based systems and smart phone applications, have been developed to allow individuals to self-monitor their behavior digitally. These programs offer an advantage over traditional self-report modalities in that they can provide users with direct feedback about dietary and/or physical activity adherence levels and thereby assist them in real-time decision making. This article describes the use of an Internet-based computerized tracking system (CTS) that was developed specifically for the POUNDS LOST study, a 2-year randomized controlled trial designed to test the efficacy of four macronutrient diets for weight and fat reduction in healthy, overweight men and women (body mass index range = 25.0–39.9 kg/m2). The CTS served many functions in this study, including data collection, dietary and exercise assessment and feedback, messaging system, and report generation. Across all groups, participants with high usage of the CTS during the initial 8 weeks lost greater amounts of weight than participants with low usage (8.7% versus 5.5% of initial body weight, respectively; p < .001) at week 32. Rates of CTS utilization were highest during the first year of this 2-year intervention, and utilization of the CTS declined steadily over time. The unique features of the CTS combined with technological developments, such as smart phone applications, offer significant potential to improve the user's self-monitoring experience and adherence to health promotion programs designed specifically for individuals with obesity and type 2 diabetes.
Fluorescence Lifetime Imaging Microscopy of Intracellular Glucose Dynamics
Authors: Veetil Jithesh V. , Jin Sha , Ye Kaiming
Published: January 2014

Background:

One of the major hurdles in studying diabetes pathophysiology is the lack of adequate methodology that allows for direct and real-time determination of glucose transport and metabolism in cells and tissues. In this article, we present a new methodology that adopts frequency-domain fluorescence lifetime imaging microscopy (FD-FLIM) to visualize and quantify the dynamics of intracellular glucose within living cells using a biosensor protein based on fluorescence resonance energy transfer (FRET).

Method:

The biosensor protein was developed by fusing a FRET pair, an AcGFP1 donor and a mCherry acceptor to N- and C- termini of a mutant glucose-binding protein (GBP), respectively. The probe was expressed and biosynthesized inside the cells, offering continuous monitoring of glucose dynamics in real time through fluorescence lifetime imaging microscopy (FLIM) measurement.

Results:

We transfected the deoxyribonucleic acid of the AcGFP1-GBP-mCherry sensor into murine myoblast cells, C2C12, and continuously monitored the changes in intracellular glucose concentrations in response to the variation in extracellular glucose, from which we determined glucose uptake and clearance rates. The distribution of intracellular glucose concentration was also characterized. We detected a high glucose concentration in a region close to the cell membrane and a low glucose concentration in a region close to the nucleus. The monoexponential decay of AcGFP1 was distinguished using FD-FLIM.

Conclusions:

This work enables continuous glucose monitoring (CGM) within living cells using FD-FLIM and a biosensor protein. The sensor protein developed offers a new means for quantitatively analyzing glucose homeostasis at the cellular level. Data accumulated from these studies will help increase our understanding of the pathology of diabetes.
Fluorescence Resonance Energy Transfer Glucose Sensor from Site-Specific Dual Labeling of Glucose/Galactose Binding Protein Using Ligand Protection
Authors: Hsieh Helen V. , Sherman Douglas B. , Andaluz Sandra A. , Amiss Terry J. , Pitner J. Bruce
Published: January 2014

Background:

Site-selective modification of proteins at two separate locations using two different reagents is highly desirable for biosensor applications employing fluorescence resonance energy transfer (FRET), but few strategies are available for such modification. To address this challenge, sequential selective modification of two cysteines in glucose/galactose binding protein (GGBP) was demonstrated using a technique we call “ligand protection.”

Method:

In this technique, two cysteines were introduced in GGBP and one cysteine is rendered inaccessible by the presence of glucose, thus allowing sequential attachment of two different thiol-reactive reagents. The mutant E149C/A213C/L238S was first labeled at E149C in the presence of the ligand glucose. Following dialysis and removal of glucose, the protein was labeled with a second dye, either Texas Red (TR) C5 bromoacetamide or TR C2 maleimide, at the second site, A213C.

Results:

Changes in glucose-dependent fluorescence were observed that were consistent with FRET between the nitrobenzoxadiazole and TR fluorophores. Comparison of models and spectroscopic properties of the C2 and C5 TR FRET constructs suggests the greater rigidity of the C2 linker provides more efficient FRET.

Conclusions:

The ligand protection strategy provides a simple method for labeling GGBP with two different fluorophores to construct FRET-based glucose sensors with glucose affinity within the human physiological glucose range (1–30 mM). This general strategy may also have broad utility for other protein-labeling applications.
In-Vitro Performance of the Enlite Sensor in Various Glucose Concentrations during Hypobaric and Hyperbaric Conditions
Authors: Adolfsson Peter , Örnhagen Hans , Eriksson Bengt M. , Gautham Raghavendhar , Jendle Johan
Published: January 2014

Background:

There is a need for reliable methods of glucose measurement in different environmental conditions. The objective of this in vitro study was to evaluate the performance of the Enlite® Sensor when connected to either the iPro™ Continuous Glucose Monitor recording device or the Guardian® REAL-Time transmitting device, in hypobaric and hyperbaric conditions.

Methods:

Sixteen sensors connected to eight iPro devices and eight Guardian REAL-Time devices were immersed in three beakers containing separate glucose concentrations: 52, 88, and 207 mg/dl (2.9, 4.9, and 11.3 mmol/liter). Two different pressure tests were conducted: A hypobaric test, corresponding to maximum 18000 ft/5500 m height, and a hyperbaric test, corresponding to maximum 100 ft/30 m depth. The linearity of the sensor signals in the different conditions was evaluated.

Results:

The sensors worked continuously, and the sensor signals were collected without interruption at all pressures tested. When comparing the input signals for glucose (ISIGs) and the different glucose concentrations during altered pressure, linearity ( R2) of 0.98 was found. During the hypobaric test, significant differences ( p < .005) were seen when comparing the ISIGs during varying pressure at two of the glucose concentrations (52 and 207 mg/dl), whereas no difference was seen at the 88 mg/dl glucose concentration. During the hyperbaric test, no differences were found.

Conclusions:

The Enlite Sensors connected to either the iPro or the Guardian REAL-Time device provided values continuously. In hyperbaric conditions, no significant differences were seen during changes in ambient pressure; however, during hypobaric conditions, the ISIG was significantly different in the low and high glucose concentrations.
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: Danne Thomas , Forst Thomas , Deinhard Jürgen , Rose Ludger , Moennig Elisabeth , Haupt Axel
Published: January 2014

Background:

Injection compliance is a major problem in patients with type 1 diabetes. Increased compliance with mealtime insulin injections significantly improves metabolic control. Using an insulin pen with memory function might facilitate corrective dosing to avoid postprandial blood glucose peaks and therefore might improve overall glycemic control.

Methods:

This randomized, open-label, 24-week multicenter study evaluated if patients with inadequately controlled type 1 diabetes [hemoglobin A1c (HbA1c) ≥ 8%] who were randomized to use the HumaPen® Memoir™, an insulin pen device with memory function, for their mealtime insulin injections achieved superior glycemic control (HbA1c change from baseline) than patients who used the conventional device HumaPen Luxura™. Hemoglobin A1c, hypoglycemia, and pen acceptance were assessed at baseline and after 12 and 24 weeks.

Results:

of 263 patients randomized, 257 were eligible for analysis: HumaPen Memoir 129, HumaPen Luxura 128; mean [standard deviation (SD)] baseline HbA1c 9.09% (0.99%); mean (SD) age 39.8 (16.5) years; 87.9% ≥18 years old; and mean (SD) diabetes duration 16.0 (11.2) years. Least square mean (95% confidence interval) changes of HbA1c up to week 24 were not significantly different between the HumaPen Memoir [0.43% (-0.59%,-0.28%)] and the HumaPen Luxura group [0.48% (0.64%, 0.32%); p = .669]. The overall incidence of hypoglycemic episodes did not differ significantly between groups ( p = .982). Average satisfaction with insulin delivery was high in both groups.

Conclusions:

In this patient sample, usage of a memory function pen was not associated with superior glycemic control, suggesting that adherence to mealtime injection schedules was not improved in a relevant manner. The memory function might be helpful for specific patient populations only, e.g., children or forgetful patients.
Hyperglycemia Control of the Nil Per Os Patient in the Intensive Care Unit: Introduction of a Simple Subcutaneous Insulin Algorithm
Authors: Kim Sarah , Rushakoff Robert J. , Sullivan Mary , Windham Heidemarie
Published: January 2014

Background:

Diabetes patients in the intensive care unit (ICU) and either nil per os, on enteral feedings, or on total parenteral nutrition are often treated with sliding-scale insulin (despite lack of evidence showing benefit) or intravenous insulin (IVI) infusion, a nursing intensive procedure requiring hourly glucose measurements, and insulin rate adjustments. We introduced a subcutaneous insulin algorithm (SQIA) that would equal the glucose goals for IVI but have the simplicity of q4 hour adjustable sliding-scale insulin.

Methods:

As part of a quality improvement project, we developed a simple SQIA that titrates insulin to the requirements of the individual patient. Glucoses were monitored q4 h and SQ rapid-acting insulin administered based on both the previous insulin dose and current glucose level. Fourteen consecutive hyperglycemic patients admitted to ICU-A were placed on the SQIA. Glucose and insulin data were also obtained on 18 patients in an identical ICU-B who were treated with the usual IVI protocol, which is q1-2 h.

Results:

Duration on the SQIA was 4.5 ± 0.6 days (range 0.8–7) and on IVI 1.9 ± 0.6 days (range 0.25–9). Due to difference in length on protocols, only data for the first 3 days could be statistically compared. During this time, the mean ± standard error of glucoses for the SQ and IV groups were 157.3 ± 3.8 and 157.0 ± 2.2 (not significant). No differences were seen in hypoglycemia rates.

Conclusions:

A simple SQIA allows insulin doses to be adjusted to the individual patient's needs and meet current ICU goals for glycemic control. Its adoption may reduce the workload of nurses.
Effect of Dexamethasone-Loaded Poly(Lactic-Co-Glycolic Acid) Microsphere/Poly(Vinyl Alcohol) Hydrogel Composite Coatings on the Basic Characteristics of Implantable Glucose Sensors
Authors: Wang Yan , Vaddiraju Santhisagar , Qiang Liangliang , Xu Xiaoming , Papadimitrakopoulos Fotios , Burgess Diane J.
Published: January 2014

Background:

Hydrogels alone and in combination with microsphere drug delivery systems are being considered as biocompatible coatings for implantable glucose biosensors to prevent/minimize the foreign body response. Previously, our group has demonstrated that continuous release of dexamethasone from poly(lactic-co-glycolic acid) (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel composites can successfully prevent foreign body response at the implantation site. The objective of this study was to investigate the effect of this composite coating on sensor functionality.

Methods:

The PLGA microsphere/PVA hydrogel coatings were prepared and applied to glucose biosensors. The swelling properties of the composite coatings and their diffusivity to glucose were evaluated as a function of microsphere loading. Sensor linearity, response time, and sensitivity were also evaluated as a function of coating composition.

Results:

The PLGA microsphere/PVA hydrogel composite coating did not compromise sensor linearity (sensors were linear up to 30 mM), which is well beyond the physiological glucose range (2 to 22 mM). The sensor response time did increase in the presence of the coating (from 10 to 19 s); however, this response time was still less than the average reported values. Although the sensitivity of the sensors decreased from 73 to 62 nA/mM glucose when the PLGA microsphere loading in the PVA hydrogel changed from 0 to 100 mg/ml, this reduced sensitivity is acceptable for sensor functionality. The changes in sensor response time and sensitivity were due to changes in glucose permeability as a result of the coatings. The embedded PLGA microspheres reduced the fraction of bulk water present in the hydrogel matrix and consequently reduced glucose diffusion.

Conclusions:

This study demonstrates that the PLGA microsphere/PVA hydrogel composite coatings allow sufficient glucose diffusion and sensor functionality and therefore may be utilized as a smart coating for implantable glucose biosensors to enhance their in vivo functionality.
Detection of Trace Glucose on the Surface of a Semipermeable Membrane Using a Fluorescently Labeled Glucose-Binding Protein: A Promising Approach to Noninvasive Glucose Monitoring
Authors: Ge Xudong , Rao Govind , Kostov Yordan , Kanjananimmanont Sunsanee , Viscardi Rose M. , Woo Hyung , Tolosa Leah
Published: January 2014

Background:

Our motivation for this study was to develop a noninvasive glucose sensor for low birth weight neonates. We hypothesized that the underdeveloped skin of neonates will allow for the diffusion of glucose to the surface where it can be sampled noninvasively. On further study, we found that measurable amounts of glucose can also be collected on the skin of adults.

Method:

Cellulose acetate dialysis membrane was used as surrogate for preterm neonatal skin. Glucose on the surface was collected by saline-moistened swabs and analyzed with glucose-binding protein (GBP). The saline-moistened swab was also tested in the neonatal intensive care unit. Saline was directly applied on adult skin and collected for analysis with two methods: GBP and high-performance anion-exchange chromatography (HPAEC).

Results:

The amount of glucose on the membrane surface was found (1) to accumulate with time but gradually level off, (2) to be proportional to the swab dwell time, and (3) the concentration of the glucose solution on the opposite side of the membrane. The swab, however, failed to absorb glucose on neonatal skin. On direct application of saline onto adult skin, we were able to measure by HPAEC and GBP the amount of glucose collected on the surface. Blood glucose appears to track transdermal glucose levels.

Conclusions:

We were able to measure trace amounts of glucose on the skin surface that appear to follow blood glucose levels. The present results show modest correlation with blood glucose. Nonetheless, this method may present a noninvasive alternative to tracking glucose trends.
First Clinical Evaluation of a New Percutaneous Optical Fiber Glucose Sensor for Continuous Glucose Monitoring in Diabetes
Authors: Müller Achim Josef , Knuth Monika , Nikolaus Katharina Sibylle , Krivánek Roland , Küster Frank , Hasslacher Christoph
Published: January 2014

Background:

This article describes a new fiber-coupled, percutaneous fluorescent continuous glucose monitoring (CGM) system that has shown 14 days of functionality in a human clinical trial.

Method:

The new optical CGM system (FiberSense) consists of a transdermal polymer optical fiber containing a biochemical glucose sensor and a small fluorescence photometer optically coupled to the fiber. The glucose-sensitive optical fiber was implanted in abdominal and upper-arm subcutaneous tissue of six diabetes patients and remained there for up to 14 days. The performance of the system was monitored during six visits to the study center during the trial. Blood glucose changes were induced by oral carbohydrate intake and insulin injections, and capillary blood glucose samples were obtained from the finger tip. The data were analyzed using linear regression and the consensus error grid analysis.

Results:

The FiberSense worn at the upper arm exhibited excellent results during 14 wearing days, with an overall mean absolute relative difference (MARD) of 8.3% and 94.6% of the data in zone A of the consensus error grid. At the abdominal application site, FiberSense resulted in a MARD of 11.4 %, with 93.8% of the data in zone A.

Conclusions:

The FiberSense CGM system provided consistent, reliable measurements of subcutaneous glucose levels in human clinical trial patients with diabetes for up to 14 days.
Single-Walled Carbon Nanotube-Based Near-Infrared Optical Glucose Sensors toward In Vivo Continuous Glucose Monitoring
Authors: Yum Kyungsuk , McNicholas Thomas P. , Mu Bin , Strano Michael S.
Published: January 2014

This article reviews research efforts on developing single-walled carbon nanotube (SWNT)-based near-infrared (NIR) optical glucose sensors toward long-term in vivo continuous glucose monitoring (CGM). We first discuss the unique optical properties of SWNTs and compare SWNTs with traditional organic and nanoparticle fluorophores regarding in vivo glucose-sensing applications. We then present our development of SWNT-based glucose sensors that use glucose-binding proteins and boronic acids as a high-affinity molecular receptor for glucose and transduce binding events on the receptors to modulate SWNT fluorescence. Finally, we discuss opportunities and challenges in translating the emerging technology of SWNT-based NIR optical glucose sensors into in vivo CGM for practical clinical use.
Hypoglycemia-Associated Electroencephalogram and Electrocardiogram Changes Appear Simultaneously
Authors: Larsen Anine , Højlund Kurt , Poulsen Mikael Kjær , Madsen Rasmus Elsborg , Juhl Claus B.
Published: January 2014

Background:

Tight glycemic control in type 1 diabetes mellitus (T1DM) may be accomplished only if severe hypoglycemia can be prevented. Biosensor alarms based on the body's reactions to hypoglycemia have been suggested. In the present study, we analyzed three lead electrocardiogram (ECG) and single-channel electroencephalogram (EEG) in T1DM patients during hypoglycemia.

Materials and Methods:

Electrocardiogram and EEG recordings during insulin-induced hypoglycemia in nine patients were used to assess the presence of ECG changes by heart rate, and estimates of QT interval (QTc) and time from top of T wave to end of T wave corrected for heartbeat interval and EEG changes by extraction of the power of the signal in the delta, theta, and alpha bands. These six features were assessed continuously to determine the time between changes and severe hypoglycemia.

Results:

QT interval changes and EEG theta power changes were detected in six and eight out of nine subjects, respectively. Rate of false positive calculations was one out of nine subjects for QTc and none for EEG theta power. Detection time medians (i.e., time from significant changes to termination of experiments) was 13 and 8 min for the EEG theta power and QTc feature, respectively, with no significant difference (p = .25).

Conclusions:

Severe hypoglycemia is preceded by changes in both ECG and EEG features in most cases. Electroencephalogram theta power may be superior with respect to timing, sensitivity, and specificity of severe hypoglycemia detection. A multiparameter algorithm that combines data from different biosensors might be considered.
Professional Continuous Glucose Monitoring in Subjects with Type 1 Diabetes: Retrospective Hypoglycemia Detection
Authors: Jensen Morten Hasselstrøm , Christensen Toke Folke , Tarnow Lise , Mahmoudi Zeinab , Johansen Mette Dencker , Hejlesen Ole Kristian
Published: January 2014

Background:

An important task in diabetes management is detection of hypoglycemia. Professional continuous glucose monitoring (CGM), which produces a glucose reading every 5 min, is a powerful tool for retrospective identification of unrecognized hypoglycemia. Unfortunately, CGM devices tend to be inaccurate, especially in the hypoglycemic range, which limits their applicability for hypoglycemia detection. The objective of this study was to develop an automated pattern recognition algorithm to detect hypoglycemic events in retrospective, professional CGM.

Method:

Continuous glucose monitoring and plasma glucose (PG) readings were obtained from 17 data sets of 10 type 1 diabetes patients undergoing insulin-induced hypoglycemia. The CGM readings were automatically classified into a hypoglycemic group and a nonhypoglycemic group on the basis of different features from CGM readings and insulin injection. The classification was evaluated by comparing the automated classification with PG using sample-based and event-based sensitivity and specificity measures.

Results:

With an event-based sensitivity of 100%, the algorithm produced only one false hypoglycemia detection. The sample-based sensitivity and specificity levels were 78% and 96%, respectively.

Conclusions:

The automated pattern recognition algorithm provides a new approach for detecting unrecognized hypoglycemic events in professional CGM data. The tool may assist physicians and diabetologists in conducting a more thorough evaluation of the diabetes patient's glycemic control and in initiating necessary measures for improving glycemic control.
Automated Glycemic Pattern Analysis: Overcoming Diabetes Clinical Inertia
Authors: Schwartz Frank L. , Marling Cynthia R. , Shubrook Jay
Published: January 2014

The OneTouch® Verio™ IQ Meter with PatternAlert™ Technology has been approved by the U.S. Food and Drug Administration as the first self-glucose monitor that can automatically determine glycemic patterns [high and low pre-meal blood glucose (BG)] for health care providers (HCPs) and patients. In this issue of Journal of Diabetes Science and Technology, Katz and coauthors demonstrate that this device was more accurate and quicker in detecting abnormal glucose patterns than the review by HCPs of 30-day handwritten BG logs and that its interpretations were positively accepted by the HCPs. Continued development of automated pattern analysis and decision-support software to overcome the “data-overload” associated with intensive glucose monitoring and diabetes management will reduce clinical inertia and could dramatically improve diabetes outcomes.
Hypoglycemia Early Alarm Systems Based on Recursive Autoregressive Partial Least Squares Models
Authors: Bayrak Elif Seyma , Turksoy Kamuran , Cinar Ali , Quinn Lauretta , Littlejohn Elizabeth , Rollins Derrick
Published: January 2014

Background:

Hypoglycemia caused by intensive insulin therapy is a major challenge for artificial pancreas systems. Early detection and prevention of potential hypoglycemia are essential for the acceptance of fully automated artificial pancreas systems. Many of the proposed alarm systems are based on interpretation of recent values or trends in glucose values. In the present study, subject-specific linear models are introduced to capture glucose variations and predict future blood glucose concentrations. These models can be used in early alarm systems of potential hypoglycemia.

Method:

A recursive autoregressive partial least squares (RARPLS) algorithm is used to model the continuous glucose monitoring sensor data and predict future glucose concentrations for use in hypoglycemia alarm systems. The partial least squares models constructed are updated recursively at each sampling step with a moving window. An early hypoglycemia alarm algorithm using these models is proposed and evaluated.

Results:

Glucose prediction models based on real-time filtered data has a root mean squared error of 7.79 and a sum of squares of glucose prediction error of 7.35% for six-step-ahead (30 min) glucose predictions. The early alarm systems based on RARPLS shows good performance. A sensitivity of 86% and a false alarm rate of 0.42 false positive/day are obtained for the early alarm system based on six-step-ahead predicted glucose values with an average early detection time of 25.25 min.

Conclusions:

The RARPLS models developed provide satisfactory glucose prediction with relatively smaller error than other proposed algorithms and are good candidates to forecast and warn about potential hypoglycemia unless preventive action is taken far in advance.
Food and Drug Administration Regulation of Diabetes-Related mHealth Technologies
Authors: Brooke M. Jason , Thompson Bradley Merrill
Published: January 2014

mHealth smartphone applications (apps) offer great promise for managing people with diabetes, as well as those with prediabetes. But to realize that potential, industry needs to get clarity from the U.S. Food and Drug Administration (FDA) regarding the scope of its regulatory oversight. Certain smartphone apps, when properly understood, simply help people live healthier lives, assisting with dietary choices, monitoring exercise, and recording other factors important to overall health. The manufacturers of such apps, in an effort to promote their products but also to educate customers, might wish to explain how using the app can help reduce the risk of developing diabetes. Right now, though, the mere mention of the disease “diabetes” would cause the app to be regulated by the FDA. Such regulation, we submit, discourages the kind of education and motivational messages that our country needs to stem the tide of this disease. Further, should the app simply receive data from a blood glucose meter and graph that data for easier comprehension by the patient, the app would become a class II medical device that requires FDA clearance. Again, we submit that such simple software functionality should not be so discouraged. In this article, we identify the issues that we believe need to be clarified by the FDA in order to unleash the potential of mHealth technology in the diabetes space.
Patenting Carboxyformin in the United States: How Does it Work and What Does it Mean?
Authors: Sheehan Meghan E. , Wagner Louis F.
Published: January 2014

Carboxyformin, a new biguanide, shows promise as a treatment for type 2 diabetes mellitus (attributes assumed for the purpose of this article). But is a carboxyformin-based therapeutic formulation patentable? And if the formulation is patentable, what protection is afforded by the patent? This article examines the patent prosecution process, beginning with the initial discovery and continuing through the issuance of the patent. The article also briefly discusses issues of patent infringement and considers whether the inventor is able to practice his invention and whether he is able to keep others from the unauthorized use of his invention.
Legal and Regulatory Challenges Currently Facing Diabetes Treatment Providers and Related Durable Medical Equipment Suppliers
Authors: Liles Robert
Published: January 2014

It has been estimated that 24 million Americans have diabetes, many of whom are Medicare beneficiaries. These individuals carefully monitor their blood glucose levels primarily through the use of in-home blood glucose testing kits. Although the test is relatively simple, the cumulative expense of providing glucose test strips and lancets to patients is ever increasing, both to the Medicare program and to uninsured individuals who must pay out-of-pocket for these testing supplies. This article discusses the diabetes durable medical equipment (DME) coverage under Part B Medicare, the establishment and role of DME Medicare administrative contractors, and national and local coverage requirements for diabetes DME suppliers. This article also discusses the federal government's ongoing concerns regarding the improper billing of diabetes testing supplies. To protect the Medicare Trust Fund, the federal government has contracted with multiple private entities to conduct reviews and audits of questionable Medicare claims. These private sector contractors have conducted unannounced site visits of DME supplier offices, interviewed patients and their families, placed suppliers on prepayment review, and conducted extensive postpayment audits of prior paid Medicare claims. In more egregious administrative cases, Medicare contractors have recommended that problematic providers and/or DME suppliers have their Medicare numbers suspended or, in some instances, revoked. More serious infractions can lead to civil or criminal liability. In the final part of this article, we will examine the future of enforcement efforts by law enforcement and Medicare contractors and the importance of understanding and complying with federal laws when ordering and supplying diabetes testing strips and lancets.
Acceptability and Utility of the mySentry Remote Glucose Monitoring System
Authors: Kaiserman Kevin , Buckingham Bruce A. , Prakasam Gnanagurudasan , Gunville Fred , Slover Robert H. , Wang Yongyin , Nguyen Xuan , Welsh John B.
Published: January 2014

Background:

The mySentry system (Medtronic Inc.) is the first to amplify and relay continuous glucose monitoring (CGM) and insulin pump data to a remote site within the house. Its usability and acceptability were evaluated in families having a child with type 1 diabetes.

Methods:

Each enrolled family included a child (age 7–17 years) who used a Paradigm REAL-Time Revel sensor-augmented insulin pump (Medtronic). After a 1-week run-in phase, families set up and used the mySentry system for a 3-week study phase. Opinion surveys were completed by parents, and pump and CGM data were collected and analyzed retrospectively. No formal hypothesis testing was performed, and the study was not powered to detect changes in nocturnal glycemia.

Results:

Thirty-five families completed the study. Enrolled children (61.1% female) had a mean (± standard deviation) age of 11.9 ± 2.70 years and a mean age at initiation of pump therapy of 7.1 ± 3.19 years. Baseline survey results indicated that most parents were fearful of their unawareness of their children's nocturnal glucose excursions. The mySentry system met the predefined acceptability criteria for general experience, product usability, and training materials. There were no unanticipated device-related adverse effects. Among children who experienced nocturnal hypo- or hyperglycemic episodes in both phases of the study, there was a trend toward less frequent and less prolonged episodes during mySentry use.

Conclusion:

The mySentry system met all predefined criteria for acceptability and did not demonstrate safety issues. Alerting parents to abnormal glucose values or trends may attenuate nocturnal hypoglycemia and hyperglycemia by prompting appropriate and timely intervention.
Performance of a New Meter Designed for Assisted Monitoring of Blood Glucose and Point-of-Care Testing
Authors: MacRury Sandra , Srinivasan Aparna , Mahoney John J.
Published: January 2014

Background:

Blood glucose (BG) meters used for assisted monitoring of blood glucose (AMBG) require different attributes compared with meters designed for home use. These include safety considerations (i.e., minimized risk of blood-borne pathogen transmission), capability for testing multiple blood sample types, and enhanced performance specifications. The OneTouch® Verio™Pro+ BG meter is designed to incorporate all of these attributes.

Methods:

Meter accuracy was assessed in clinical studies with arterial, venous, and capillary blood samples with a hematocrit range of 22.9–59.8%. The effect of interferents, including anticoagulants, on accuracy was evaluated. The meter disinfection protocol was validated, and instructions for use and user acceptance of the system were assessed.

Results:

A total of 97% (549/566) of BG measures from all blood sample types and 95.5% (191/200) of arterial blood samples were within ±12 mg/dl or 12.5% of reference measurements. The system was unaffected by 4 anticoagulants and 57 of 59 endogenous and exogenous compounds; it was affected by 2 compounds: Pralidoxime iodide and xylose. Bleach wipes were sufficient to disinfect the meter. Users felt that the meter's quality control (QC) prompts would help them to comply with regulatory requirements.

Conclusion:

The meter provided accurate measurements of different blood samples over a wide hematocrit range and was not affected by 57 physiologic and therapeutic compounds. The QC prompts and specific infection-mitigating design further aid to make this meter system practical for AMBG in care facilities.