bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Drugstore Safe? Counterfeit Diabetes Products on the Shelves
Authors: Cheng May M.
Published: January 2014

It is no longer possible to identify counterfeit medical products, including medications and devices, by simply checking packaging and labeling. Improvements in technology have made it cheaper and easier to produce fake packaging and labels, making it nearly impossible for consumers and authorities to detect counterfeits without conducting tests on the products themselves, as illustrated by the sale of over one million counterfeit blood glucose test strips sold to unsuspecting U.S. consumers at drugstores in more than 35 states and in other countries around the world in the fall of 2006. The pricier the drugs, the more counterfeiters seek to mimic them to maximize returns, victimizing those patients at highest risk who rely on life-saving medications. The interconnected global economy and advances in technology that benefit legitimate businesses and consumers is also benefiting counterfeiters. As pharmaceutical and medical device companies use new technologies and work with governments and international agencies to combat counterfeiting on a global scale, a public awareness campaign is needed to educate consumers to protect themselves.
Hypoglycemia Prediction with Subject-Specific Recursive Time-Series Models
Authors: Eren-Oruklu Meriyan , Cinar Ali , Quinn Lauretta
Published: January 2014

Background:

Avoiding hypoglycemia while keeping glucose within the narrow normoglycemic range (70–120 mg/dl) is a major challenge for patients with type 1 diabetes. Continuous glucose monitors can provide hypoglycemic alarms when the measured glucose decreases below a threshold. However, a better approach is to provide an early alarm that predicts a hypoglycemic episode before it occurs, allowing enough time for the patient to take the necessary precaution to avoid hypoglycemia.

Methods:

We have previously proposed subject-specific recursive models for the prediction of future glucose concentrations and evaluated their prediction performance. In this work, our objective was to evaluate this algorithm further to predict hypoglycemia and provide early hypoglycemic alarms. Three different methods were proposed for alarm decision, where (A) absolute predicted glucose values, (B) cumulative-sum (CUSUM) control chart, and (C) exponentially weighted moving-average (EWMA) control chart were used. Each method was validated using data from the Diabetes Research in Children Network, which consist of measurements from a continuous glucose sensor during an insulin-induced hypoglycemia. Reference serum glucose measurements were used to determine the sensitivity to predict hypoglycemia and the false alarm rate.

Results:

With the hypoglycemic threshold set to 60 mg/dl, sensitivity of 89, 87.5, and 89% and specificity of 67, 74, and 78% were reported for methods A, B, and C, respectively. Mean values for time to detection were 30 ± 5.51 (A), 25.8 ± 6.46 (B), and 27.7 ± 5.32 (C) minutes.

Conclusions:

Compared to the absolute value method, both CUSUM and EWMA methods behaved more conservatively before raising an alarm (reduced time to detection), which significantly decreased the false alarm rate and increased the specificity.
Hypoglycemia Alarm Enhancement Using Data Fusion
Authors: Skladnev Victor N. , Tarnavskii Stanislav , McGregor Thomas , Ghevondian Nejhdeh , Gourlay Steve , Jones Timothy W.
Published: January 2014

Background:

The acceptance of closed-loop blood glucose (BG) control using continuous glucose monitoring systems (CGMS) is likely to improve with enhanced performance of their integral hypoglycemia alarms. This article presents an in silico analysis (based on clinical data) of a modeled CGMS alarm system with trained thresholds on type 1 diabetes mellitus (T1DM) patients that is augmented by sensor fusion from a prototype hypoglycemia alarm system (HypoMon®). This prototype alarm system is based on largely independent autonomic nervous system (ANS) response features.

Methods:

Alarm performance was modeled using overnight BG profiles recorded previously on 98 T1DM volunteers. These data included the corresponding ANS response features detected by HypoMon (AiMedics Pty. Ltd.) systems. CGMS data and alarms were simulated by applying a probabilistic model to these overnight BG profiles. The probabilistic model developed used a mean response delay of 7.1 minutes, measurement error offsets on each sample of ± standard deviation (SD) = 4.5 mg/dl (0.25 mmol/liter), and vertical shifts (calibration offsets) of ± SD = 19.8 mg/dl (1.1 mmol/liter). Modeling produced 90 to 100 simulated measurements per patient. Alarm systems for all analyses were optimized on a training set of 46 patients and evaluated on the test set of 56 patients. The split between the sets was based on enrollment dates. Optimization was based on detection accuracy but not time to detection for these analyses. The contribution of this form of data fusion to hypoglycemia alarm performance was evaluated by comparing the performance of the trained CGMS and fused data algorithms on the test set under the same evaluation conditions.

Results:

The simulated addition of HypoMon data produced an improvement in CGMS hypoglycemia alarm performance of 10% at equal specificity. Sensitivity improved from 87% (CGMS as stand-alone measurement) to 97% for the enhanced alarm system. Specificity was maintained constant at 85%. Positive predictive values on the test set improved from 61 to 66% with negative predictive values improving from 96 to 99%. These enhancements were stable within sensitivity analyses. Sensitivity analyses also suggested larger performance increases at lower CGMS alarm performance levels.

Conclusion:

Autonomic nervous system response features provide complementary information suitable for fusion with CGMS data to enhance nocturnal hypoglycemia alarms.
Alarm Characterization for Continuous Glucose Monitors Used as Adjuncts to Self-Monitoring of Blood Glucose
Authors: McGarraugh Geoffrey
Published: January 2014

Background:

Continuous glucose monitoring (CGM) devices available in the United States are approved for use as adjuncts to self-monitoring of blood glucose (SMBG). Alarm evaluation in the Clinical and Laboratory Standards Institute (CLSI) guideline for CGM does not specifically address devices that employ both CGM and SMBG. In this report, an alarm evaluation method is proposed for these devices.

Method:

The proposed method builds on the CLSI method using data from an in-clinic study of subjects with type 1 diabetes. CGM was used to detect glycemic events, and SMBG was used to determine treatment. To optimize detection of a single glucose level, such as 70 mg/dl, a range of alarm threshold settings was evaluated. The alarm characterization provides a choice of alarm settings that trade off detection and false alarms. Detection of a range of high glucose levels was similarly evaluated.

Results:

Using low glucose alarms, detection of 70 mg/dl within 30 minutes increased from 64 to 97% as alarm settings increased from 70 to100 mg/dl, and alarms that did not require treatment (SMBG >85 mg/dl) increased from 18 to 52%. Using high glucose alarms, detection of 180 mg/dl within 30 minutes increased from 87 to 96% as alarm settings decreased from 180 to 165 mg/dl, and alarms that did not require treatment (SMBG <180 mg/dl) increased from 24 to 42%.

Conclusion:

The proposed alarm evaluation method provides information for choosing appropriate alarm thresholds and reflects the clinical utility of CGM alarms.
Alarm Characterization for a Continuous Glucose Monitor That Replaces Traditional Blood Glucose Monitoring
Authors: McGarraugh Geoffrey
Published: January 2014

Background:

Continuous glucose monitoring (CGM) devices available in the United States are approved for use as adjuncts to self-monitoring of blood glucose (SMBG); all CGM alarms require SMBG confirmation before treatment. In this report, an analysis method is proposed to determine the CGM threshold alarm accuracy required to eliminate SMBG confirmation.

Method:

The proposed method builds on the Clinical and Laboratory Standards Institute (CLSI) guideline for evaluating CGM threshold alarms using data from an in-clinic study of subjects with type 1 diabetes. The CLSI method proposes a maximum time limit of ±30 minutes for the detection of hypo- and hyperglycemic events but does not include limits for glucose measurement accuracy. The International Standards Organization (ISO) standard for SMBG glucose measurement accuracy (ISO 15197) is ±15 mg/dl for glucose <75 mg/dl and ±20% for glucose ≥75 mg/dl. This standard was combined with the CLSI method to more completely characterize the accuracy of CGM alarms.

Results:

Incorporating the ISO 15197 accuracy margins, FreeStyle Navigator® CGM system alarms detected 70 mg/dl hypoglycemia within 30 minutes at a rate of 70.3%, with a false alarm rate of 11.4%. The device detected high glucose in the range of 140–300 mg/dl within 30 minutes at an average rate of 99.2%, with a false alarm rate of 2.1%.

Conclusion:

Self-monitoring of blood glucose confirmation is necessary for detecting and treating hypoglycemia with the FreeStyle Navigator CGM system, but at high glucose levels, SMBG confirmation adds little incremental value to CGM alarms.
Analytical and Clinical Performance of Blood Glucose Monitors
Authors: Boren Suzanne Austin , Clarke William L.
Published: January 2014

Background:

The objective of this study was to understand the level of performance of blood glucose monitors as assessed in the published literature.

Methods:

Medline from January 2000 to October 2009 and reference lists of included articles were searched to identify eligible studies. Key information was abstracted from eligible studies: blood glucose meters tested, blood sample, meter operators, setting, sample of people (number, diabetes type, age, sex, and race), duration of diabetes, years using a glucose meter, insulin use, recommendations followed, performance evaluation measures, and specific factors affecting the accuracy evaluation of blood glucose monitors.

Results:

Thirty-one articles were included in this review. Articles were categorized as review articles of blood glucose accuracy (6 articles), original studies that reported the performance of blood glucose meters in laboratory settings (14 articles) or clinical settings (9 articles), and simulation studies (2 articles). A variety of performance evaluation measures were used in the studies. The authors did not identify any studies that demonstrated a difference in clinical outcomes. Examples of analytical tools used in the description of accuracy (e.g., correlation coefficient, linear regression equations, and International Organization for Standardization standards) and how these traditional measures can complicate the achievement of target blood glucose levels for the patient were presented. The benefits of using error grid analysis to quantify the clinical accuracy of patient-determined blood glucose values were discussed.

Conclusions:

When examining blood glucose monitor performance in the real world, it is important to consider if an improvement in analytical accuracy would lead to improved clinical outcomes for patients. There are several examples of how analytical tools used in the description of self-monitoring of blood glucose accuracy could be irrelevant to treatment decisions.
Siphon Effects on Continuous Subcutaneous Insulin Infusion Pump Delivery Performance
Authors: Zisser Howard C. , Bevier Wendy , Dassau Eyal , Jovanovič Lois
Published: January 2014

Background:

The objective was to quantify hydrostatic effects on continuous subcutaneous insulin infusion (CSII) pumps during basal and bolus insulin delivery.

Methods:

We tested CSII pumps from Medtronic Diabetes (MiniMed 512 and 515), Smiths Medical (Deltec Cozmo 1700), and Insulet (OmniPod) using insulin aspart (Novolog, Novo Nordisk). Pumps were filled and primed per manufacturer's instructions. The fluid level change was measured using an inline graduated glass pipette (100 μl) when the pipette was moved in relation to the pump (80 cm Cosmo and 110 cm Medtronics) and when level. Pumps were compared during 1 and 5 U boluses and basal insulin delivery of 1.0 and 1.5 U/h.

Results:

Pronounced differences were seen during basal delivery in pumps using 80–100 cm tubing. For the 1 U/h rate, differences ranged from 74.5% of the expected delivery when the pumps were below the pipettes and pumping upward to 123.3% when the pumps were above the pipettes and pumping downward. For the 1.5 U/h rate, differences ranged from 86.7% to 117.0% when the pumps were below or above the pipettes, respectively. Compared to pumps with tubing, OmniPod performed with significantly less variation in insulin delivery.

Conclusions:

Changing position of a conventional CSII pump in relation to its tubing results in significant changes in insulin delivery. The siphon effect in the tubing may affect the accuracy of insulin delivery, especially during low basal rates. This effect has been reported when syringe pumps were moved in relation to infusion sites but has not been reported with CSII pumps.
No Higher Dose Requirements with Insulin Detemir than Glargine in Type 2 Diabetes: A Crossover, Double-Blind, and Randomized Study Using Continuous Glucose Monitoring
Authors: King Allen B.
Published: January 2014

Background:

In a previous publication we reported no difference in the 24-hour glucose response between two basal analog insulins, detemir and glargine, when taken once a day in type 2 diabetes mellitus (T2DM). We now report the dose comparison observed within this randomized, double-blind, crossover study.

Method:

Of 36 patients on basal insulin and other noninsulin treatments, 29 completed the study. Both insulins were given once a day at 8 pm and no food was taken between 6 pm and the following morning. The dose was titrated daily by continuous glucose monitoring (CGM) until the basal glucose (between 12 and 6 am) was <120 mg/dl but not >5% of CGM readings <70 mg/dl. Subjects were then crossed over to the other insulin and titrated similarly.

Results:

Glucose goals were achieved in all subjects. The mean dosage was 0.26 U/kg with very few subjects requiring >0.4 U/kg. Only 2 required an absolute dose less than 10 U/day and all others required more, some considerably higher. Of the 29 subjects, 7 required a greater, 6 a smaller, and 16 the same dose of detemir compared to glargine.

Conclusions:

When given once daily in T2DM and titrated using CGM to the same fasting glucose, there was no difference in the glucose response between basal insulins during the basal titration period (4–10 hours after injection) nor during the entire 24-hour period following the injection. Further, the mean dosage to achieve this glucose goal was the same with both insulins.
Aluminum Gallium Nitride (GaN)/GaN High Electron Mobility Transistor-Based Sensors for Glucose Detection in Exhaled Breath Condensate
Authors: Chu Byung Hwan , Kang Byoung Sam , Hung Sheng Chun , Chen Ke Hung , Ren Fan , Sciullo Andrew , Gila Brent P. , Pearton Stephen J.
Published: January 2014

Background:

Immobilized aluminum gallium nitride (AlGaN)/GaN high electron mobility transistors (HEMTs) have shown great potential in the areas of pH, chloride ion, and glucose detection in exhaled breath condensate (EBC). HEMT sensors can be integrated into a wireless data transmission system that allows for remote monitoring. This technology offers the possibility of using AlGaN/GaN HEMTs for extended investigations of airway pathology of detecting glucose in EBC without the need for clinical visits.

Methods:

HEMT structures, consisting of a 3-μm-thick undoped GaN buffer, 30-Å-thick Al03Ga07N spacer, and 220-Å-thick silicon-doped Al03Ga07N cap layer, were used for fabricating the HEMT sensors. The gate area of the pH, chloride ion, and glucose detection was immobilized with scandium oxide (Sc2O3), silver chloride (AgCl) thin film, and zinc oxide (ZnO) nanorods, respectively.

Results:

The Sc2O3-gated sensor could detect the pH of solutions ranging from 3 to 10 with a resolution of ∼0.1 pH. A chloride ion detection limit of 10−8 M was achievedt with a HEMT sensor immobilized with the AgCl thin film. The drain-source current of the ZnO nanorod-gated AlGaN/GaN HEMT sensor immobilized with glucose oxidase showed a rapid response of less than 5 seconds when the sensor was exposed to the target glucose in a buffer with a pH value of 7.4. The sensor could detect a wide range of concentrations from 0.5 nM to 125 μ M.

Conclusion:

There is great promise for using HEMT-based sensors to enhance the detection sensitivity for glucose detection in EBC. Depending on the immobilized material, HEMT-based sensors can be used for sensingt different materials. These electronic detection approaches with rapid response and good repeatability show potential for the investigation of airway pathology. The devices can also be integrated into a wireless data transmission system for remote monitoring applications. This sensor technology could use the exhaled breath condensate to measure the glucose concentration for diabetic applications.
An Intensive Insulinotherapy Mobile Phone Application Built on Artificial Intelligence Techniques
Authors: Curran Kevin , Nichols Eric , Xie Ermai , Harper Roy
Published: January 2014

Background:

Software to help control diabetes is currently an embryonic market with the main activity to date focused mainly on the development of noncomputerized solutions, such as cardboard calculators or computerized solutions that use “flat” computer models, which are applied to each person without taking into account their individual lifestyles. The development of true, mobile device-driven health applications has been hindered by the lack of tools available in the past and the sheer lack of mobile devices on the market. This has now changed, however, with the availability of pocket personal computer handsets.

Method:

This article describes a solution in the form of an intelligent neural network running on mobile devices, allowing people with diabetes access to it regardless of their location. Utilizing an easy to learn and use multipanel user interface, people with diabetes can run the software in real time via an easy to use graphical user interface. The neural network consists of four neurons. The first is glucose. If the user's current glucose level is within the target range, the glucose weight is then multiplied by zero. If the glucose level is high, then there will be a positive value multiplied to the weight, resulting in a positive amount of insulin to be injected. If the user's glucose level is low, then the weights will be multiplied by a negative value, resulting in a decrease in the overall insulin dose.

Results:

A minifeasibility trial was carried out at a local hospital under a consultant endocrinologist in Belfast. The short study ran for 2 weeks with six patients. The main objectives were to investigate the user interface, test the remote sending of data over a 3G network to a centralized server at the university, and record patient data for further proofing of the neural network. We also received useful feedback regarding the user interface and the feasibility of handing real-world patients a new mobile phone. Results of this short trial confirmed to a large degree that our approach (which also can be known as intensive insulinotherapy) has value and perhaps that our neural network approach has implications for future intelligent insulin pumps.

Conclusions:

Currently, there is no software available to tell people with diabetes how much insulin to inject in accordance with their lifestyle and individual inputs, which leads to adjustments in software predictions on the amount of insulin to inject. We have taken initial steps to supplement the knowledge and skills of health care professionals in controlling insulin levels on a daily basis using a mobile device for people who are less able to manage their disease, especially children and young adults.
Obesity Epidemic Requires Federal Intervention: “Healthy Kids” Key to Nation's Healthy Future
Authors: Moran James P.
Published: January 2014

The Healthy Kids Act (H.R. 4053) legislation does three things: (1) establishes an office of Childhood Overweight and Obesity Prevention and Treatment within the Department of Health and Human Services to provide information and promote action on healthy eating, (2) institutes a three-tier system for labeling foods, and (3) enables regulatory action to curb food commercials targeting children.
Practical Aspects of Insulin Pen Devices
Authors: Pearson Teresa L.
Published: January 2014

Insulin pen devices have several advantages over the traditional vial-and-syringe method of insulin delivery, including improved patient satisfaction and adherence, greater ease of use, superior accuracy for delivering small doses of insulin, greater social acceptability, and less reported injection pain. In recent years, pens have become increasingly user-friendly, and some models are highly intuitive to use, requiring little or no instruction. Despite this progress, uptake of these devices in the United States has not matched that in many other areas of the world. There is a need for improved awareness of the current characteristics of insulin pen devices among United States health care professionals. Knowledge of the design improvements that have been incorporated into pens, both to address patient needs and as a result of the improved technology behind the device mechanics, is essential to promoting the use of insulin pen devices. This review highlights some of the practical aspects of pen use and discusses the factors to be considered when selecting among different insulin pens.
Lessons Learned during the Development of HumaPen® Memoir™, an Insulin Pen with a Memory Feature
Authors: Breslin Stuart D. , Ignaut Debra A. , Boyd Douglas E.
Published: January 2014

Insulin pens are developed to address specific needs of diabetes patients for their pens, such as ease of use, portability, and discreetness. Like many consumer-based products, the development of insulin pens can pose significant challenges to the development team in that they must balance substantial accuracy requirements with aesthetic desires. The HumaPen® Memoir™ team learned valuable lessons throughout the development process that may be worth highlighting. A keen understanding of the unmet needs of the patient population and a skillfully planned product generation map are critical to successful device development. A development team must decide whether to use a Quality Functional Deployment or system engineering-based development plan and, additionally, recognize where proof of concept ends and product development begins to maintain a strict timeline for the project. A proficiency in understanding and managing technical risk is critical to ensure a timely and high-quality product launch to the marketplace.
Analysis of Symposium Articles on Insulin Pen Devices and Alternative Insulin Delivery Methods
Authors: Dang Devra K. , Lee Jennifer
Published: January 2014

Insulin therapy is a fundamental component of diabetes management, yet there is often resistance to insulin initiation by both prescribers and patients. A barrier to insulin use is the perceived shortcomings with the traditional vial-and-syringe administration method (inconvenience, difficulty of use, association with disease and addiction, etc.). This symposium in the journal discusses the advantages of alternative insulin delivery methods, primarily insulin pen devices. Although these administration methods, especially insulin pens, have some clear advantages over the vial/syringe, there are also limitations to their use and careful patient selection and education are still needed.
Bolus Calculator with Nutrition Database Software, a New Concept of Prandial Insulin Programming for Pump Users
Authors: Pańkowska Ewa , Błazik Marlena
Published: January 2014

Bolus calculators are effective tools in controlling blood glucose levels in patients treated with insulin. Diabetics is a new software devised for patients to facilitate and improve self-managing for prandial insulin dosing and for better controlling food intake. This device contains two integral parts: A nutrition database and a bolus calculator. The algorithm is based on a formula in which carbohydrate (CHO) and either fat and/or protein (FP) products are engulfed in insulin. The insulin dose setting is programmed individually for CHO in a normal bolus (N-W) and for FP in a square-wave bolus (S-W). The device calculates the dose of insulin for N-W or S-W, suggests the optimal kind of bolus, and indicates the timing in hours for an S-W bolus. In addition, this calculator, which contains a nutrition database and insulin dosing software, helps determine the correct type of necessary boluses for selected foods.
Basal Insulin Requirements on Continuous Subcutaneous Insulin Infusion during the First 12 Months after Diagnosis of Type 1 Diabetes Mellitus
Authors: Ramchandani Neesha , Ellis Mary Kristine , Jain Shobhit , Bhandari Sonal , Anhalt Henry , Maclaren Noel K. , Ten Svetlana
Published: January 2014

Introduction:

While the endogenous first-phase insulin response has disappeared by the time of diagnosis of type 1 diabetes mellitus (T1DM), anecdotal evidence suggests that these patients can continue to have a second-phase insulin response during the first 12 months after diagnosis. We hypothesized that patients who are started on continuous subcutaneous insulin infusion (CSII) at the time of diagnosis of T1DM would have a lower basal insulin requirement than the 40–60% usually expected.

Methods:

We analyzed 38 patients with T1DM, age 9.9 ± 6.4 years, 71% male, who were started on CSII within the first month of diagnosis.

Results:

Average basal insulin requirements were 47–49% of total daily dose during the first 12 months after diagnosis and decreased from 0.30 U/kg/day at diagnosis to 0.20 U/kg/day by 12 months. Baseline percentage of basal insulin was significantly correlated with hemoglobin A1c at baseline and at six months. The percentage of basal insulin requirement at 12 months after diagnosis was significantly correlated with baseline body mass index (BMI) and current BMI. No other correlations between percentage of basal insulin requirements and any other factors were seen.

Conclusion:

Our data suggest that, even though some endogenous insulin production remains during the first year after diagnosis of T1DM, the distribution of basal versus total daily insulin requirements remains the same as in the general population of people with diabetes. There may be benefits to starting patients on a higher basal rate at time of diagnosis for overall glycemic control during the first six months. Further research is needed to optimize starting insulin doses to maximize their potential in preserving beta-cell function.
Continuous Glucose Monitoring System in a Rural Intensive Care Unit: A Pilot Study Evaluating Accuracy and Acceptance
Authors: Jacobs Brooke , Phan Kim , Bertheau Leonard , Dogbey Godwin , Schwartz Frank , Shubrook Jay
Published: January 2014

Background:

Glucose management in an intensive care unit (ICU) is labor-intensive. A continuous glucose monitoring system (CGMS) has the potential to improve efficiency and safety in this setting. The goal of this study was to determine if the Medtronic Guardian® REAL-Time CGMS was accurate and tolerated by patients in a rural hospital ICU unit.

Method:

Differences between individual finger stick blood glucose (FSBG) and CGMS values were compared to American Diabetes Association (ADA) and International Organization for Standardization (ISO) standards. Continuous glucose monitoring system accuracy was evaluated over four ranges: <75, 75–140, 140–200, and >200 mg/dl. Other accuracy measures [mean absolute deviation (MAD), mean absolute relative difference (MARD), and coefficient of linear regression of CGMS on FSBG] were calculated. Nursing staff and patients were surveyed regarding use of the CGMS in the ICU.

Results:

Twenty-nine participants had 320 FSBG and corresponding CGMS readings. Sixty-two percent of participants were admitted with diabetic ketoacidosis (DKA). Two hundred and thirteen (66.6%) were accurate within the ISO standard, whereas only 70 out of 320 (21.9%) were within the 5% ADA standard. The CGMS was most accurate in euglycemia. Technical difficulties, such as adequate time for “wetting” and calibration of electrodes, arose with the sensors. The MAD was 28.3 mg/dl, the MRAD was 17.4%, and the linear regression coefficient of CGMS on FSBG was 0.834 ( p < 0.001).

Conclusions:

The CGMS is well tolerated by ICU patients but, at present, is not sufficiently accurate to be used for therapeutic decisions in the acute setting, particularly in patients with diabetic ketoacidosis. There is a need to find resolution to the technical issues regarding electrode “wetting” and calibration if CGMS use in the ICU setting is to provide an effective means of diabetes care and management.
Blood Glucose Regulation during Prolonged, Submaximal, Continuous Exercise: A Guide for Clinicians
Authors: Goodwin Matthew L.
Published: January 2014

Management of many chronic diseases now includes regular exercise as part of a viable treatment plan. Exercise in the form of prolonged, submaximal, continuous exercise (SUBEX; i.e., ~30 min to 1 h, ~40–70% of maximal oxygen uptake) is often prescribed due to its relatively low risk, the willingness of patients to undertake, its efficacy, its affordability, and its ease of prescription. Specifically, patients who are insulin resistant or that have type 2 diabetes mellitus may benefit from regular exercise of this type. During this type of exercise, muscles dramatically increase glucose uptake as the liver increases both glycogenolysis and gluco-neogenesis. While a redundancy of mechanisms is at work to maintain blood glucose concentration ([glucose]) during this type of exercise, the major regulator of blood glucose is the insulin/glucagon response. At exercise onset, blood [glucose] transiently rises before beginning to decline after ~30 min, causing a subsequent decline in blood [insulin] and rise in blood glucagon. This leads to many downstream effects, including an increase in glucose output from the liver to maintain adequate glucose in the blood to fuel both the muscles and the brain. Finally, when analyzing blood [glucose], consideration should be given to nutritional status (postabsorptive versus postprandial) as well as both what the analyzer measures and the type of sample used (plasma versus whole blood). In view of both prescribing exercise to patients as well as designing studies that perturb glucose homeostasis, it is imperative that clinicians and researchers alike understand the controls of blood glucose homeostasis during SUBEX.
High-Sensitivity C-Reactive Protein Predicts Cardiovascular Risk in Diabetic and Nondiabetic Patients: Effects of Insulin-Sensitizing Treatment with Pioglitazone
Authors: Pfützner Andreas , Schöndorf Thomas , Hanefeld Markolf , Forst Thomas
Published: January 2014

Systemic inflammatory activity has turned out to play a key pathogenic role in vascular atherosclerosis, insulin resistance, and type 2 diabetes mellitus. Inflammatory biomarkers may therefore be a valuable tool for risk evaluation. Among them, the best evidence to date supports the use of high-sensitivity C-reactive protein (hs-CRP) to monitor insulin resistance and cardiovascular risk in diabetic and nondiabetic individuals. Data suggest that hs-CRP may also participate directly in the process of atherogenesis. A growing number of clinical trials tested the hypothesis that antidiabetic drugs specifically targeting insulin resistance could benefit individuals by reducing inflammation, atherogenesis, and thus cardiovascular risk. One such class are the thiazolidinediones (pioglitazone and rosiglitazone). These agents act as selective ligands of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ). This article reviewed published data on hs-CRP changes with the thiazolidinedione agent pioglitazone. Here we found pronounced insulin-sensitizing and anti-inflammatory properties in different clinical settings, including diabetic and nondiabetic individuals. Coadministration of pioglitazone to antilipidemic statin therapy resulted in additional effects on low-grade inflammation, and hs-CRP reduction has been demonstrated to occur independently of glucose lowering. The anti-inflammatory effect appeared to be a rapid physiologic reaction on PPARγ activation and could be observed within a short-term interval after starting pioglitazone therapy. In summary, clinical study results underline the benefit of an early insulin resistance treatment to oppose systemic vascular inflammation and cardiometabolic syndrome in patients with elevated levels of high-sensitivity C-reactive protein.
Practical Considerations in the Use of Real-Time Continuous Glucose Monitoring Alerts
Authors: Mastrototaro John , Welsh John B. , Lee Scott
Published: January 2014

Background:

The safety and efficacy of real-time (RT) continuous glucose monitoring (CGM) systems in the management of type 1 diabetes are increasingly apparent. Clinical trials have demonstrated the utility of these systems in lowering hemoglobin A1c, minimizing hypoglycemia, and reducing glycemic variability. These RT systems allow patients to conveniently monitor their glucose levels by displaying concentration and trending information. Several of these RT systems provide preset alerts that sound when absolute glucose thresholds are reached. Additionally, some systems allow for predictive algorithm-based alerts that incorporate rates of change. However, clinical trials have identified significant noncompliance in the use of these devices, most notably in the pediatric and adolescent populations. A retrospective review of CGM reports shows that many patients set high and low alert thresholds at levels that result in frequent alerts, potentially resulting in patient nuisance, dismissal of consequential alerts, and eventual product abandonment. Therefore, setting the alert thresholds at appropriate high and low settings can determine the balance between either a perceived benefit by the patient and their long-term use of CGM systems or annoyance to the patient and discontinuation.

Conclusion:

Care should be taken to set CGM alerts at levels that result in a manageable number of notifications per day. In some cases, providers should consider not using alerts at all or consider using broad targets when initiating CGM to maximize alert specificity. Real-time CGM is safe and generally well tolerated; however, individualization of alert settings is necessary maximize the system's benefits and patient adherence.
Wound Inflammatory Index: A “Proof of Concept” Study to Assess Wound Healing Trajectory
Authors: Bharara Manish , Schoess Jeffrey , Nouvong Aksone , Armstrong David G.
Published: January 2014

Diabetes around the globe results in one major limb amputation every 30 seconds, over 2500 limbs lost per day. The underlying pathophysiology sometimes leads to a chronic Inflammatory stage, which may prevent appropriate healing, and therefore, the need for a clear strategy for assessing and classifying wounds and wound healing cannot be overstated. Temperature is a surrogate marker for inflammation. Quantitative thermography using a numerical index provides a useful way to assess wound healing. Advances in technology have afforded the availability of low-cost, high-resolution thermal imaging systems, which can be used to quantify sensitive changes on the skin surface and may be particularly useful to develop monitoring strategies for wounds. This article provides a standardized technique for calculating a thermal index (TI) supported with a case report from assessment of a diabetic foot ulcer. In this single case study, the TI/wound Inflammatory index indicates a shift from negative to positive ( p < .05) before it reaches zero.
Digital Planimetry Results in More Accurate Wound Measurements: A Comparison to Standard Ruler Measurements
Authors: Rogers Lee C. , Bevilacqua Nicholas J. , Armstrong David G. , Andros George
Published: January 2014

Background:

Cutaneous wound measurements are important to track the healing of a wound and direct appropriate therapy. The most commonly used method to calculate wound area is an estimation by multiplying the longest length by the widest width. Other devices can provide an accurate and precise measurement of the true area (TA). This study aim was to compare wound areas calculated by computerized planimetry with standard area estimation by multiplying the longest length by the widest width ( l × w).

Methods:

We reviewed the wound records of 10 patients with circular or oval wounds and estimated the area with the l × w method. We compared this with the TA obtained by a specialized planimetric camera.

Results:

Average wound size was 4.3 cm2 by l × w estimation and 3 cm2 by TA calculation. We found the l × w method overestimated wound area an average of 41%.

Conclusions:

Standard, manual ( l × w) measurement of cutaneous wounds inaccurately overestimates wound area by roughly 40%.
Toward an Injectable Continuous Osmotic Glucose Sensor
Authors: Johannessen Erik , Krushinitskaya Olga , Sokolov Andrey , Häfliger Philipp , Hoogerwerf Arno , Hinderling Christian , Kautio Kari , Lenkkeri Jaakko , Strömmer Esko , Kondratyev Vasily , Tønnessen Tor Inge , Mollnes Tom Eirik , Jakobsen Henrik , Zimmer Even , Akselsen Bengt
Published: January 2014

Background:

The growing pandemic of diabetes mellitus places a stringent social and economic burden on the society. A tight glycemic control circumvents the detrimental effects, but the prerogative is the development of new more effective tools capable of longterm tracking of blood glucose (BG) in vivo. Such discontinuous sensor technologies will benefit from an unprecedented marked potential as well as reducing the current life expectancy gap of eight years as part of a therapeutic regime.

Method:

A sensor technology based on osmotic pressure incorporates a reversible competitive affinity assay performing glucose-specific recognition. An absolute change in particles generates a pressure that is proportional to the glucose concentration. An integrated pressure transducer and components developed from the silicon micro- and nanofabrication industry translate this pressure into BG data.

Results:

An in vitro model based on a 3.6 × 8.7 mm large pill-shaped implant is equipped with a nanoporous membrane holding 4–6 nm large pores. The affinity assay offers a dynamic range of 36–720 mg/dl with a resolution of ±16 mg/dl. An integrated 1 × 1 mm2 large control chip samples the sensor signals for data processing and transmission back to the reader at a total power consumption of 76 μW.

Conclusions:

Current studies have demonstrated the design, layout, and performance of a prototype osmotic sensor in vitro using an affinity assay solution for up to four weeks. The small physical size conforms to an injectable device, forming the basis of a conceptual monitor that offers a tight glycemic control of BG.
Proficiency Testing of Human Leukocyte Antigen-DR and Human Leukocyte Antigen-DQ Genetic Risk Assessment for Type 1 Diabetes Using Dried Blood Spots
Authors: Dantonio Paul , Meredith-Molloy Nancy , Hagopian William A. , She Jin Xiong , Akolkar Beena , Cordovado Suzanne K. , Hendrix Miyono , Henderson L. Omar , Hannon W. Harry , Vogt Robert F.
Published: January 2014

Background:

The plurality of genetic risk for developing type 1 diabetes mellitus (T1DM) lies within the genes that code for the human leukocyte antigens (HLAs). Many T1DM studies use HLA genetic risk assessment to identify higher risk individuals, and they often conduct these tests on dried blood spots (DBSs) like those used for newborn bloodspot screening. One such study is The Environmental Determinants of Diabetes in the Young (TEDDY), a long-term prospective study of environmental risk factors. To provide quality assurance for T1DM studies that employ HLA genetic risk assessment, the Centers for Disease Control and Prevention (CDC) conducts both a voluntary quarterly Proficiency testing (VQPT) program available to any laboratory and a mandatory annual Proficiency testing (PT) challenge for TEDDY laboratories.

Methods:

Whole blood and DBS samples with a wide range of validated HLA-DR and HLA-DQ genotypes were sent to the participating laboratories. Results were evaluated on the basis of both the reported haplotypes and the HLA genetic risk assessment.

Results:

Of the reported results from 24 panels sent out over six years in the VQPT, 94.7% (857/905) were correctly identified with respect to the relevant HLA-DR or HLA-DQ alleles, and 96.4% (241/250) were correctly categorized for risk assessment significant improvement was seen over the duration of this program, usually reaching 100% correct categorization during the last three years. Of 1154 reported results in four TEDDY PT challenges, 1153 (99.9%) were correctly identified for TEDDY eligibility.

Conclusions:

The different analytical methods used by T1DM research centers all provided accurate (>99%) results for genetic risk assessment. The two CDC PT programs documented the validity of the various approaches to screening and contributed to overall quality assurance.
An Analysis of Data Management Tools for Diabetes Self-Management: Can Smart Phone Technology Keep Up?
Authors: Ciemins Elizabeth , Coon Patricia , Sorli Christopher
Published: January 2014

In this issue of Journal of Diabetes Science and Technology, Rao and colleagues present a comparison of three iPhone diabetes data management applications: the Diamedic Diabetes Logbook, Blood Sugar Diabetes Control, and WaveSense Diabetes Manager. These applications provide patients the ability to enter blood glucose readings manually, view graphs and simple statistics, and email data to health care providers. While these applications show promise, they are limited in their current forms. All require manual data entry and none convert insulin-to-carbohydrate ratios to insulin dose. Future development of these types of technology should consider integration with blood glucose meters and expanded calculation capabilities, as well as monitoring of other risk factors, e.g., blood pressure and lipids, and tracking of preventive examinations, e.g., eye, foot, and renal.
Influence of Oral Antidiabetic Drugs on Hyperglycemic Response to Foods in Persons with Type 2 Diabetes Mellitus as Assessed by Continuous Glucose Monitoring System: A Pilot Study
Authors: Peterson Karolina , Chlup Rudolf , Zapletalova Jana , Kohnert Klaus Dieter , Kudlova Pavla , Bartek Josef , Nakladalova Marie , Doubravova Blanka , Seckar Pavel
Published: January 2014

Background:

The purpose of this prospective open-label trial was (1) to assess the Influence of oral antidiabetic drugs (OAD) on the glycemic index (GI), glucose response curves (GRCs), daily mean plasma glucose (MPG) and (2) to compare the GI of foods in persons with OAD-treated type 2 diabetes mellitus (T2DM) with the respective GI in healthy persons (HP).

Methods:

Tested foods containing 50 g of carbohydrates were eaten for breakfast and dinner after 10 and 4 h of fasting, respectively. Glycemic index, GRC, and MPG were obtained using the CGMS® System Gold™ (CGMS). In T2DM patients [n = 16; age (mean ± standard error) 56.0 ± 2.25 years], foods were tested four times: tests 1, 2, and 3 were performed within one week in which placebo was introduced on day 2, and test 4 was carried out five weeks after reintroduction of OAD. Glycemic indexes, GRC, and MPG from tests 1, 2, 3, and 4 were compared. In a control group of 20 HP (age 24.4 ± 0.71 years), the mean GIs were calculated as the mean from 20 subject-related GIs.

Results:

In T2DM patients, subject-related assessment of GIs, GRC, and MPG distinguished persons with and without OAD effect. Nevertheless, the group-related GIs and the MPG on days 2, 8, and 39 showed no significant difference. There was no significant difference between the GIs in OAD-treated T2DM patients (test 4) versus HP (except in apple baby food). Glucose response curves were significantly larger in T2DM patients (test 4) versus HP.

Conclusions:

Determination of GRC and subject-related GI using the CGMS appears to be a potential means for the evaluation of efficacy of OAD treatment. Further studies are underway.
Proteomic Technologies for the Discovery of Type 1 Diabetes Biomarkers
Authors: Zhi Wenbo , Purohit Sharad , Carey Colleen , Wang Meiyao , She Jin-Xiong
Published: January 2014

In this review, we discuss several important issues concerning the discovery of protein biomarkers for complex human diseases, with a focus on type 1 diabetes. Serum or plasma is the first choice of specimen due to its richness in biological information and relatively easy availability. It is a challenging task to comprehensively characterize the serum/plasma proteome because of the large dynamic range of protein concentration. Therefore, sample pretreatment is required in order to explore the low- to medium-abundance proteins contained in serum/ plasma. In this regard, enrichment of low-abundance proteins using random hexapeptide library beads has distinct advantages over the traditional immune-depletion methods, including higher efficiency, higher binding capacity, and lower cost. In-depth mining of serum/plasma proteome using different separation techniques have also been evaluated and are discussed in this review. Overall, the shotgun proteomics—multidimensional separation of digested peptides followed by mass spectrometry analysis—is highly Efficient and therefore has become a preferred method for protein biomarker discovery.
Computer-Aided Learning in Insulin Pump Training
Authors: Sirotinin Sergey V. , George Charles J.
Published: January 2014

This technical report concerns a novel, computer-aided learning tool for patients with diabetes. The goal of the tool is to make training in the use of an insulin pump “painless,” practical, effective, and educationally rewarding. This learning tool (or application) is unique because it

uses a virtual pump to facilitate learning and allow the patient to practice pump operation presents training tasks in a standardized format, and provides corrective feedback to help patients better understand and manage their diabetes.

The application's acceptability was surveyed by 126 health care professionals who are experienced in diabetes education and certified in pump training. Results suggest that use of Insulet's OmniPod® Interactive Training is associated with increased training efficiency and promotes a positive attitude toward insulin pump therapy.